Journal: Cardiovasc Diabetol

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Abstract
<div><h4>Acid sphingomyelinase promotes diabetic cardiomyopathy via NADPH oxidase 4 mediated apoptosis.</h4><i>Liu R, Duan T, Yu L, Tang Y, ... Wang C, Fang WJ</i><br /><b>Background</b><br />Increased acid sphingomyelinase (ASMase) activity is associated with insulin resistance and cardiac dysfunction. However, the effects of ASMase on diabetic cardiomyopathy (DCM) and the molecular mechanism(s) underlying remain to be elucidated. We here investigated whether ASMase caused DCM through NADPH oxidase 4-mediated apoptosis.<br /><b>Methods and results</b><br />We used pharmacological and genetic approaches coupled with study of murine and cell line samples to reveal the mechanisms initiated by ASMase in diabetic hearts. The protein expression and activity of ASMase were upregulated, meanwhile ceramide accumulation was increased in the myocardium of HFD mice. Inhibition of ASMase with imipramine (20 mg Kg<sup>-1</sup> d<sup>-1</sup>) or siRNA reduced cardiomyocyte apoptosis, fibrosis, and mitigated cardiac hypertrophy and cardiac dysfunction in HFD mice. The similar effects were observed in cardiomyocytes treated with high glucose (HG, 30 mmol L<sup>-1</sup>) + palmitic acid (PA, 100 μmol L<sup>-1</sup>) or C16 ceramide (CER, 20 μmol L<sup>-1</sup>). Interestingly, the cardioprotective effect of ASMase inhibition was not accompanied by reduced ceramide accumulation, indicating a ceramide-independent manner. The mechanism may involve activated NADPH oxidase 4 (NOX4), increased ROS generation and triggered apoptosis. Suppression of NOX4 with apocynin prevented HG + PA and CER incubation induced Nppb and Myh7 pro-hypertrophic gene expression, ROS production and apoptosis in H9c2 cells. Furthermore, cardiomyocyte-specific ASMase knockout (ASMase<sup>Myh6KO</sup>) restored HFD-induced cardiac dysfunction, remodeling, and apoptosis, whereas NOX4 protein expression was downregulated.<br /><b>Conclusions</b><br />These results demonstrated that HFD-mediated activation of cardiomyocyte ASMase could increase NOX4 expression, which may stimulate oxidative stress, apoptosis, and then cause metabolic cardiomyopathy.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 02 Feb 2023; 22:25</small></div>
Liu R, Duan T, Yu L, Tang Y, ... Wang C, Fang WJ
Cardiovasc Diabetol: 02 Feb 2023; 22:25 | PMID: 36732747
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<div><h4>Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors.</h4><i>Scisciola L, Taktaz F, Fontanella RA, Pesapane A, ... Vanderheyden M, Barbieri M</i><br /><b>Background</b><br />Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation.<br /><b>Methods</b><br />To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters.<br /><b>Results</b><br />Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes.<br /><b>Conclusions</b><br />In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 02 Feb 2023; 22:24</small></div>
Scisciola L, Taktaz F, Fontanella RA, Pesapane A, ... Vanderheyden M, Barbieri M
Cardiovasc Diabetol: 02 Feb 2023; 22:24 | PMID: 36732760
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<div><h4>Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis.</h4><i>Myasoedova VA, Parisi V, Moschetta D, Valerio V, ... Genovese S, Poggio P</i><br /><b>Background</b><br />Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction.<br /><b>Methods</b><br />A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses.<br /><b>Results</b><br />All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively).<br /><b>Conclusions</b><br />Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 31 Jan 2023; 22:23</small></div>
Myasoedova VA, Parisi V, Moschetta D, Valerio V, ... Genovese S, Poggio P
Cardiovasc Diabetol: 31 Jan 2023; 22:23 | PMID: 36721184
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<div><h4>Sex-specific differences in the effect of the atherogenic index of plasma on prediabetes and diabetes in the NHANES 2011-2018 population.</h4><i>Shi Y, Wen M</i><br /><b>Background</b><br />Although a great deal of scientific evidence on the epidemiological risk factors for diabetes and prediabetes has been accumulated, there is still insufficient evidence to explore sex-related differences. The aim of this study was to examine sex-specific differences in the effect of the atherogenic index of plasma (AIP) on prediabetes and diabetes.<br /><b>Methods</b><br />This cross-sectional study included data from 10099 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included prediabetes and diabetes defined by the 2013 American Diabetes Association guidelines.<br /><b>Results</b><br />The median age (mean ± SD) was 48.51 ± 18.42 years, and the average value (SD) of the AIP was - 0.09 (0.34). The prevalence of prediabetes was 40.24%, and that of diabetes was 21.32%. Overall, there was a significant positive association between the AIP and prediabetes and diabetes (per 1-unit increment in the AIP: OR, 2.49; 95% CI 1.75, 3.54). The multivariate logistic regression model demonstrated that for each unit increment in the AIP, the prediabetes and diabetes prevalence increased 4.96-fold among female participants (OR 4.96, 95% CI 2.68, 9.18) but not among male participants. We found that the AIP was not related to the prevalence of prediabetes or diabetes (OR 1.41; 95% CI 0.87, 2.29) among males. There was an interaction between sex and the AIP (P for interaction < 0.0001).<br /><b>Conclusions</b><br />This study showed that a higher AIP was significantly associated with an increased prevalence of prediabetes and diabetes, and the above relationships occurred only among women and not men.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 30 Jan 2023; 22:19</small></div>
Abstract
<div><h4>Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis.</h4><i>Ekmejian A, Sritharan H, Selvakumar D, Venkateshka V, ... Ward M, Bhindi R</i><br /><b>Background</b><br />Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of  > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR.<br /><b>Methods</b><br />We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR  > 0.8 were included. The primary end point was MACE.<br /><b>Results</b><br />The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35-2.04, p =  < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06-2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20-2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07-4.05, p = 0.03).<br /><b>Conclusions</b><br />For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL:  https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022367312.<br /><br />© 2023. Crown.<br /><br /><small>Cardiovasc Diabetol: 30 Jan 2023; 22:22</small></div>
Ekmejian A, Sritharan H, Selvakumar D, Venkateshka V, ... Ward M, Bhindi R
Cardiovasc Diabetol: 30 Jan 2023; 22:22 | PMID: 36717847
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<div><h4>Improved prognosis with integrated care management including early rhythm control and healthy lifestyle modification in patients with concurrent atrial fibrillation and diabetes mellitus: a nationwide cohort study.</h4><i>Lee SR, Ahn HJ, Choi EK, Lee SW, ... Oh S, Lip GYH</i><br /><b>Background</b><br />Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) [AF-DM] have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2).<br /><b>Methods</b><br />From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups: non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4).<br /><b>Results</b><br />Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range: 2.5-6.2) years\' follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4; macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001.<br /><b>Conclusions</b><br />For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 30 Jan 2023; 22:18</small></div>
Abstract
<div><h4>Association between triglyceride-glucose index and risk of cardiovascular disease among postmenopausal women.</h4><i>Liu Q, Si F, Liu Z, Wu Y, Yu J</i><br /><b>Objective</b><br />We aimed to examine the association of triglyceride-glucose index (TyG) with risk for cardiovascular disease (CVD) among postmenopausal women.<br /><b>Methods</b><br />A total of 7741 participants met the inclusion criteria, and were included in the analysis. The TyG index was calculated as ln (triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2). The participants were classified into four groups by the quartiles of TyG index, and the Q1 group was used as the reference group. The cumulative incidence of CVD for the groups were compared using the Kaplan-Meier curves. The association between the TyG index and risk of CVD among postmenopausal women was assessed by the Cox proportional hazards models (hazard ratio [HR], 95% confidence intervals [CI]).<br /><b>Results</b><br />During a median follow-up of 12 years, a total of 383 (4.95%) participants developed incident CVD. After adjusting for potential confounding factors, a high baseline TyG index (Q4 group) was associated with higher future risk of CVD, the HR (95% CI) of CVD risk was 1.70 (1.21-2.38) in Q4 group compared with the Q1 group. Subgroup analyses showed the Q4 group was significantly associated with the risk of CVD, regardless of age at menopause (younger than 50 years; 50 years and older) and obesity status.<br /><b>Conclusions</b><br />Higher TyG index at baseline as a marker of insulin resistance (IR), is associated with higher risk of future CVD among postmenopausal women. The TyG index may serve as a simple and easy marker for early identification of high-risk individuals in the postmenopausal women.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 30 Jan 2023; 22:21</small></div>
Liu Q, Si F, Liu Z, Wu Y, Yu J
Cardiovasc Diabetol: 30 Jan 2023; 22:21 | PMID: 36717862
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<div><h4>Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease.</h4><i>Nishikido T</i><br /><AbstractText>Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 30 Jan 2023; 22:20</small></div>
Nishikido T
Cardiovasc Diabetol: 30 Jan 2023; 22:20 | PMID: 36717882
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<div><h4>Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion.</h4><i>Binsch C, Barbosa DM, Hansen-Dille G, Hubert M, ... Chadt A, Al-Hasani H</i><br /><b>Background</b><br />Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and associated with poor outcome after myocardial infarction (MI). In T2DM, cardiac metabolic flexibility, i.e. the switch between carbohydrates and lipids as energy source, is disturbed. The RabGTPase-activating protein TBC1D4 represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle by controlling glucose transporter GLUT4 translocation. A human loss-of-function mutation in TBC1D4 is associated with impaired glycemic control and elevated T2DM risk. The study\'s aim was to investigate TBC1D4 function in cardiac substrate metabolism and adaptation to MI.<br /><b>Methods</b><br />Cardiac glucose metabolism of male Tbc1d4-deficient (D4KO) and wild type (WT) mice was characterized using in vivo [<sup>18</sup>F]-FDG PET imaging after glucose injection and ex vivo basal/insulin-stimulated [<sup>3</sup>H]-2-deoxyglucose uptake in left ventricular (LV) papillary muscle. Mice were subjected to cardiac ischemia/reperfusion (I/R). Heart structure and function were analyzed until 3 weeks post-MI using echocardiography, morphometric and ultrastructural analysis of heart sections, complemented by whole heart transcriptome and protein measurements.<br /><b>Results</b><br />Tbc1d4-knockout abolished insulin-stimulated glucose uptake in ex vivo LV papillary muscle and in vivo cardiac glucose uptake after glucose injection, accompanied by a marked reduction of GLUT4. Basal cardiac glucose uptake and GLUT1 abundance were not changed compared to WT controls. D4KO mice showed mild impairments in glycemia but normal cardiac function. However, after I/R D4KO mice showed progressively increased LV endsystolic volume and substantially increased infarction area compared to WT controls. Cardiac transcriptome analysis revealed upregulation of the unfolded protein response via ATF4/eIF2α in D4KO mice at baseline. Transmission electron microscopy revealed largely increased extracellular matrix (ECM) area, in line with decreased cardiac expression of matrix metalloproteinases of D4KO mice.<br /><b>Conclusions</b><br />TBC1D4 is essential for insulin-stimulated cardiac glucose uptake and metabolic flexibility. Tbc1d4-deficiency results in elevated cardiac endoplasmic reticulum (ER)-stress response, increased deposition of ECM and aggravated cardiac damage following MI. Hence, impaired TBC1D4 signaling contributes to poor outcome after MI.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 27 Jan 2023; 22:17</small></div>
Binsch C, Barbosa DM, Hansen-Dille G, Hubert M, ... Chadt A, Al-Hasani H
Cardiovasc Diabetol: 27 Jan 2023; 22:17 | PMID: 36707786
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<div><h4>The worsening effect of anemia on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study.</h4><i>Qian WL, Xu R, Shi R, Li Y, ... Jiang L, Yang ZG</i><br /><b>Objective</b><br />To explore the additive effects of anemia on left ventricular (LV) global strains in patients with type 2 diabetes mellitus (T2DM) with or without anemia via cardiac magnetic resonance (CMR) feature tracking technology.<br /><b>Materials and methods</b><br />236 T2DM patients with or without anemia and 67 controls who underwent CMR examination were retrospectively enrolled. LV function parameters, LV global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS) were used to analyze the function and global strain of the heart. One-way analysis of variance and the chi-square test were used for intergroup analysis. Multivariable linear regression analysis was performed for the two T2DM groups to explore factors associated with LV global strains.<br /><b>Results</b><br />The T2DM group with anemia was oldest and had a lowest hemoglobin (Hb) concentration, lowest estimated glomerular filtration rate, highest LV end-systolic volume index, highest end-diastolic volume index and highest LV mass index than the control group and T2DM without anemia group (all P ≤ 0.001). Besides, The LV global peak strains in all three directions worsened successively from the control group to the T2DM without anemia group to the T2DM with anemia group (all p < 0.001). Among all clinical indices, the decrease in Hb was independently associated with the worsening in GRPS (β = 0.237, p = 0.001), GCPS (β = 0.326, p < 0.001), and GLPS (β = 0.265, p < 0.001).<br /><b>Conclusion</b><br />Anemia has additive deleterious effects on LV function and LV global strains in patients with T2DM. Regular detection and early intervention of anemia might be beneficial for T2DM patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 Jan 2023; 22:15</small></div>
Qian WL, Xu R, Shi R, Li Y, ... Jiang L, Yang ZG
Cardiovasc Diabetol: 24 Jan 2023; 22:15 | PMID: 36694151
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<div><h4>The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study.</h4><i>Goldman A, Fishman B, Twig G, Raschi E, ... Dankner R, Maor E</i><br /><b>Background</b><br />As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults.<br /><b>Methods</b><br />A retrospective, pharmacovigilance study of the FDA\'s global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR).<br /><b>Results</b><br />We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (P<sub>interaction</sub> threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults.<br /><b>Conclusion</b><br />In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 Jan 2023; 22:16</small></div>
Goldman A, Fishman B, Twig G, Raschi E, ... Dankner R, Maor E
Cardiovasc Diabetol: 24 Jan 2023; 22:16 | PMID: 36694178
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<div><h4>Diagnosis of coronary artery disease in patients with type 2 diabetes mellitus based on computed tomography and pericoronary adipose tissue radiomics: a retrospective cross-sectional study.</h4><i>Dong X, Li N, Zhu C, Wang Y, ... Wang W, Zhang T</i><br /><b>Background</b><br />Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD.<br /><b>Methods</b><br />We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 7:3. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors.<br /><b>Results</b><br />In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p < 0.001). Of these models, Model 2 had higher diagnostic efficacy for CAD than Model 1 (p < 0.001, 95% CI [0.129-0.350]). However, Model 4 did not improve the effectiveness of the identification of CAD compared to Model 2 (p = 0.776); similarly, the AUC did not significantly differ between Model 3 (AUC = 0.693) and Model 1 (AUC = 0.691, p = 0.382). Overall, Model 2 was rated better for the diagnosis of CAD in patients with T2DM.<br /><b>Conclusions</b><br />A comprehensive diagnostic model combining patient clinical risk factors with CT-based imaging parameters has superior efficacy in diagnosing the occurrence of CAD in patients with T2DM.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Jan 2023; 22:14</small></div>
Abstract
<div><h4>Accumulated hypertension burden on atrial fibrillation risk in diabetes mellitus: a nationwide population study.</h4><i>Choi J, Lee SR, Choi EK, Lee H, ... Oh S, Lip GYH</i><br /><b>Background</b><br />Patients with diabetes mellitus have an increased risk of incident atrial fibrillation (AF). The effect of accumulated hypertension burden is a less well-known modifiable risk factor. We explored the relationship between accumulated hypertension burden and incident AF in these patients.<br /><b>Methods</b><br />We evaluated data for 526,384 patients with diabetes who underwent three consecutive health examinations, between 2009 and 2012, from the Korean National Health Insurance Service. Hypertension burden was calculated by assigning points to each stage of hypertension in each health examination: 1 for stage 1 hypertension (systolic blood pressure [SBP] 130-139 mmHg; diastolic blood pressure [DBP] 80-89 mmHg); 2 for stage 2 (SBP 140-159 mmHg and DBP 90-99 mmHg); and 3 for stage 3 (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg). Patients were categorized into 10 hypertensive burden groups (0-9). Groups 1-9 were then clustered into 1-3, 4-6, and 7-9.<br /><b>Results</b><br />During a mean follow-up duration of 6.7 ± 1.7 years, AF was newly diagnosed in 18,561 (3.5%) patients. Compared to patients with hypertension burden 0, those with burden 1 to 9 showed a progressively increasing risk of incident AF: 6%, 11%, 16%, 24%, 28%, 41%, 46%, 57%, and 67% respectively. Clusters 1-3, 4-6, and 7-9 showed increased risks by 10%, 26%, and 45%, respectively, when compared to a hypertension burden of 0.<br /><b>Conclusions</b><br />Accumulated hypertension burden was associated with an increased risk of incident AF in patients with diabetes. Strict BP control should be emphasized for these patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 19 Jan 2023; 22:12</small></div>
Choi J, Lee SR, Choi EK, Lee H, ... Oh S, Lip GYH
Cardiovasc Diabetol: 19 Jan 2023; 22:12 | PMID: 36658574
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<div><h4>Cardiovascular complications in a diabetes prediction model using machine learning: a systematic review.</h4><i>Kee OT, Harun H, Mustafa N, Abdul Murad NA, ... Jaafar R, Abdullah N</i><br /><AbstractText>Prediction model has been the focus of studies since the last century in the diagnosis and prognosis of various diseases. With the advancement in computational technology, machine learning (ML) has become the widely used tool to develop a prediction model. This review is to investigate the current development of prediction model for the risk of cardiovascular disease (CVD) among type 2 diabetes (T2DM) patients using machine learning. A systematic search on Scopus and Web of Science (WoS) was conducted to look for relevant articles based on the research question. The risk of bias (ROB) for all articles were assessed based on the Prediction model Risk of Bias Assessment Tool (PROBAST) statement. Neural network with 76.6% precision, 88.06% sensitivity, and area under the curve (AUC) of 0.91 was found to be the most reliable algorithm in developing prediction model for cardiovascular disease among type 2 diabetes patients. The overall concern of applicability of all included studies is low. While two out of 10 studies were shown to have high ROB, another studies ROB are unknown due to the lack of information. The adherence to reporting standards was conducted based on the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) standard where the overall score is 53.75%. It is highly recommended that future model development should adhere to the PROBAST and TRIPOD assessment to reduce the risk of bias and ensure its applicability in clinical settings. Potential lipid peroxidation marker is also recommended in future cardiovascular disease prediction model to improve overall model applicability.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 19 Jan 2023; 22:13</small></div>
Kee OT, Harun H, Mustafa N, Abdul Murad NA, ... Jaafar R, Abdullah N
Cardiovasc Diabetol: 19 Jan 2023; 22:13 | PMID: 36658644
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<div><h4>Association of stress hyperglycemia ratio and poor long-term prognosis in patients with myocardial infarction with non-obstructive coronary arteries.</h4><i>Abdu FA, Galip J, Qi P, Zhang W, ... Xu Y, Che W</i><br /><b>Background</b><br />Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients.<br /><b>Methods</b><br />A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73-0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan-Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE.<br /><b>Results</b><br />A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P < 0.001). The Kaplan-Meier curves demonstrate that SHR3 patients had the highest MACE risk compared to SHR1 and SHR2 patients (log-rank P < 0.001). In addition, when both SHR tertiles and diabetes status were considered, those with SHR3 and diabetes had the highest hazard of MACE (log-rank P < 0.001). Multivariate Cox regression analysis showed that the SHR3 is associated with a 2.465-fold increase in the risk of MACE (adjusted HR, 2.465; 95% CI 1.461-4.159, P = 0.001). The ROC curve analysis showed that the optimal SHR cut-off value for predicting clinical MACE among MINOCA was 0.86.<br /><b>Conclusion</b><br />Our data indicates, for the first time, that SHR is independently associated with poor long-term prognosis in patients suffering from MINOCA. The optimal SHR cut-off value for predicting clinical MACE among MINOCA patients was 0.86. These findings suggest that SHR may play a potential role in the cardiovascular risk stratification of the MINOCA population.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 16 Jan 2023; 22:11</small></div>
Abdu FA, Galip J, Qi P, Zhang W, ... Xu Y, Che W
Cardiovasc Diabetol: 16 Jan 2023; 22:11 | PMID: 36647062
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<div><h4>Independent effects of the triglyceride-glucose index on all-cause mortality in critically ill patients with coronary heart disease: analysis of the MIMIC-III database.</h4><i>Zhang R, Shi S, Chen W, Wang Y, ... Liao Y, Fang Y</i><br /><b>Background</b><br />The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear.<br /><b>Methods</b><br />Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes.<br /><b>Results</b><br />A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25-2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07-2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764).<br /><b>Conclusions</b><br />The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 13 Jan 2023; 22:10</small></div>
Zhang R, Shi S, Chen W, Wang Y, ... Liao Y, Fang Y
Cardiovasc Diabetol: 13 Jan 2023; 22:10 | PMID: 36639637
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<div><h4>Sexual dimorphism in selenium deficiency is associated with metabolic syndrome and prevalence of heart disease.</h4><i>Weening EH, Al-Mubarak AA, Dokter MM, Dickstein K, ... van der Meer P, Bomer N</i><br /><b>Background</b><br />Serum selenium levels have been associated with the incidence of heart failure (HF) and signs of the metabolic syndrome. In addition, notable differences have been reported between males and females in food intake and micronutrient metabolism, possibly explaining different health outcomes.<br /><b>Objective</b><br />Our objective was to elucidate sex-specific, cross-sectional phenotypic differences in the association of serum selenium concentrations with parameters of metabolic syndrome and HF.<br /><b>Methods</b><br />We investigated data from individuals from a community-based cohort (PREVEND; N = 4288) and heart failure cohort (BIOSTAT-CHF; N = 1994). In both populations, cross-sectional analyses were performed for potential interaction (p < 0.1) between sex and serum selenium with overlapping signs and clinical parameters of the metabolic syndrome and HF.<br /><b>Results</b><br />Baseline selenium levels of the total cohort were similar between PREVEND (85.7 μg/L) and BIOSTAT-CHF (89.1 μg/L). Females with lower selenium levels had a higher BMI and increased prevalence of diabetes than females with higher selenium, in both PREVEND (p<sub>interaction</sub> < 0.001; p<sub>interaction</sub> = 0.040, resp.) and BIOSTAT-CHF (p<sub>interaction</sub> = 0.021; p<sub>interaction</sub> = 0.024, resp.), while opposite associations were observed for males. Additionally, in females, but not in males, lower selenium was associated with a higher prevalence of myocardial infarction (MI) in PREVEND (p<sub>interaction</sub> = 0.021) and BIOSTAT-CHF (p<sub>interaction</sub> = 0.084).<br /><b>Conclusion</b><br />Lower selenium was associated with a higher BMI and increased prevalence of diabetes in females, opposite to males, and was also associated with more MI in females. Interventional studies are needed to validate this observation.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Jan 2023; 22:8</small></div>
Weening EH, Al-Mubarak AA, Dokter MM, Dickstein K, ... van der Meer P, Bomer N
Cardiovasc Diabetol: 12 Jan 2023; 22:8 | PMID: 36635707
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<div><h4>Triglyceride glucose index is associated with obstructive coronary artery disease in hypertensive patients.</h4><i>Pan W, Ren Y, Yang F, Wang M, Li X, Yin D</i><br /><b>Background</b><br />Hypertension is a leading risk of coronary artery disease (CAD). Triglyceride glucose index (TyG) is a surrogate of insulin resistance (IR). Few studies explore the association between TyG and the incidence of obstructive CAD (OCAD) in hypertensive patients.<br /><b>Methods</b><br />We retrospectively screened 1841 hypertensive subjects who were free of a history of CAD and underwent coronary computed tomography angiography (CCTA) because of chest pain. TyG index was calculated as ln (fasting TG [mg/dL] * fasting glucose [mg/dL]/2). The outcome of this research was OCAD, which was defined as the presence of diameter stenosis ≥ 50% in any of the four major epicardial coronary arteries detected on CCTA.<br /><b>Results</b><br />A total of 310 (16.8%) patients developed obstructive CAD. The restricted cubic spline (RCS) analysis showed a J-shaped relationship between TyG and OCAD and the OR for OCAD increased as the TyG rose over 8.61 (OR perSD) 1.64, 95% CI 1.13-2.54, p = 0.008). After full adjustments for confounding covariates, patients with TyG index in tertile 3 (T3) had 2.12 times (95% CI 1.80 to 3.81) and in T2 had 2.01 times (95% CI 1.40 to 2.88) as high as the risk of OCAD compared with patients in T1 (p for trend = 0.001). When regarding TyG as a continuous variable, 1-SD increase elevated 49% (OR (95%CI), 1.49 (1.30-1.74)) risk of obstructive CAD (p = 0.007). This positive effect was still consistent across the subgroups (p for interaction > 0.05).<br /><b>Conclusion</b><br />TyG index was associated with the incidence of obstructive CAD in hypertensive patients.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Jan 2023; 22:9</small></div>
Pan W, Ren Y, Yang F, Wang M, Li X, Yin D
Cardiovasc Diabetol: 12 Jan 2023; 22:9 | PMID: 36635731
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<div><h4>Early longitudinal changes in left ventricular function and morphology in diabetic pigs: evaluation by 3.0T magnetic resonance imaging.</h4><i>Yan WF, Xu HY, Jiang L, Zhang L, ... Min CY, Yang ZG</i><br /><b>Background</b><br />Previous researches on large animal models of diabetic cardiomyopathy were insufficient. The aim of this study was to evaluate early changes in left ventricular (LV) function and morphology in diabetic pigs using a cardiac magnetic resonance (CMR) time-volume curve and feature tracking technique.<br /><b>Methods</b><br />Streptozotocin (STZ) was used to induce diabetic in sixteen pigs. 3.0T MRI scanned the pig\'s heart before and 2, 6, 10 and 16 months after modelling. CMR biomarkers, including time-volume curve and myocardial strain, were compared to analyse the longitudinal changes in LV function and morphology. Pearson correlation was used to evaluate the relationship between LV strain and remodelling. Cardiac specimens were obtained at 6, 10, and 16 months after modelling to observe the myocardial ultrastructural and microstructure at different courses of diabetes.<br /><b>Results</b><br />Twelve pigs developed diabetes. The 80% diastolic volume recovery rate (DVR) at 6 months after modelling was significantly higher than that before modelling (0.78 ± 0.08vs. 0.67 ± 0.15). The LV global longitudinal peak strain (GLPS) (- 10.21 ± 3.15 vs. - 9.74 ± 2.78 vs. - 9.38 ± 3.71 vs. - 8.71 ± 2.68 vs. - 6.59 ± 2.90%) altered gradually from the baseline data to 2, 6, 10 and 16 months after modelling. After 16 months of modelling, the LV remodelling index (LVRI) of pigs increased compared with that before modelling (2.19 ± 0.97 vs. 1.36 ± 0.45 g/ml). The LVRI and myocardial peak strain were correlated in diabetic pigs (r= - 0.40 to - 0.54), with GLPS being the most significant. Electron microscopy and Masson staining showed that myocardial damage and fibrosis gradually increased with the progression of the disease.<br /><b>Conclusion</b><br />Intravenous injection of STZ can induce a porcine diabetic cardiomyopathy model, mainly characterized by decreased LV diastolic function and strain changes accompanied by myocardial remodelling. The changes in CMR biomarkers could reflect the early myocardial injury of diabetic cardiomyopathy.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 10 Jan 2023; 22:6</small></div>
Yan WF, Xu HY, Jiang L, Zhang L, ... Min CY, Yang ZG
Cardiovasc Diabetol: 10 Jan 2023; 22:6 | PMID: 36627647
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<div><h4>Investigating sex-specific associations of lipid traits with type 2 diabetes, glycemic traits and sex hormones using Mendelian randomization.</h4><i>Yang G, Schooling CM</i><br /><b>Background</b><br />Low-density lipoprotein (LDL)-cholesterol is positively associated with cardiovascular disease (CVD) and inversely associated with type 2 diabetes, which could detract from lipid modification. Here, we examined whether lipid traits potentially relevant to CVD aetiology, i.e. apolipoprotein B (apoB), triglycerides (TG) and lipoprotein(a) [Lp(a)] exhibited the same associations. We investigated sex-specifically, including the role of sex hormones, because sex disparities exist in lipid profile and type 2 diabetes. We also replicated where possible.<br /><b>Methods</b><br />We used Mendelian randomization (MR) to examine sex-specific associations of apoB, TG and Lp(a) with type 2 diabetes, HbA1c, fasting insulin, fasting glucose, testosterone and estradiol in the largest relevant sex-specific genome-wide association studies (GWAS) in people of European ancestry and replicated where possible. We also assessed sex-specific associations of liability to type 2 diabetes with apoB, TG and Lp(a).<br /><b>Results</b><br />Genetically predicted apoB and Lp(a) had little association with type 2 diabetes or glycemic traits in women or men. Genetically predicted higher TG was associated with higher type 2 diabetes risk [odds ratio (OR) 1.44 per standard deviation (SD), 95% confidence interval (CI) 1.26 to 1.65], HbA1c and fasting insulin specifically in women. Higher TG was associated with lower testosterone in women and higher testosterone in men, but with lower estradiol in men and women. Genetic liability to type 2 diabetes was associated with higher TG in women, and possibly with lower apoB in men.<br /><b>Conclusions</b><br />Lipid traits potentially relevant to CVD aetiology do not exhibit contrasting associations with CVD and type 2 diabetes. However, higher TG is associated with higher type 2 diabetes risk and glycemic traits, which in turn further increases TG specifically in women, possibly driven by sex hormones.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Jan 2023; 22:3</small></div>
Abstract
<div><h4>Weight variability and cardiovascular outcomes: a systematic review and meta-analysis.</h4><i>Massey RJ, Siddiqui MK, Pearson ER, Dawed AY</i><br /><AbstractText>The association between body weight variability and the risk of cardiovascular disease (CVD) has been investigated previously with mixed findings. However, there has been no extensive study which systematically evaluates the current evidence. Furthermore, the impact of ethnicity and type 2 diabetes on this phenomena has not yet been investigated. Therefore, the aim of this study was to comprehensively evaluate the effect of weight variability on risk of CVD (any cardiovascular (CV) event, composite CV outcome, CV death, Stroke, Myocardial Infarction) and the influence of ethnicity and type 2 diabetes status on the observed association. A systematic review and meta-analysis was performed according to the meta-analyses of observational studies in epidemiology (MOOSE) guidelines. The electronic databases PubMed, Web of Science, and the Cochrane Library were searched for studies that investigated the relationship between body weight or BMI variability and CV diseases using Medical Subject Headings (MeSH) terms and keywords. The relative risks (RRs) for the outcomes were collected from studies, pooled, and analysed using a random-effects model to estimate the overall relative risk. Of 5645 articles screened, 23 studies with a total population of 15,382,537 fulfilled the prespecified criteria and were included. Individuals in the highest strata of body weight variability were found to have significantly increased risk of any CV event (RR = 1.27; 95% Confidence Interval (CI) 1.17-1.38; P < 0.0001; I<sup>2</sup> = 97.28%), cardiovascular death (RR = 1.29; 95% CI 1.03-1.60; P < 0.0001; I<sup>2</sup> = 55.16%), myocardial infarction (RR = 1.32; 95% CI 1.09-1.59; P = 0.0037; I<sup>2</sup> = 97.14%), stroke (RR = 1.21; 95% CI 1.19-1.24; P < 0.0001; I<sup>2</sup> = 0.06%), and compound CVD outcomes (RR = 1.36; 95% CI 1.08-1.73; P = 0.01; I<sup>2</sup> = 92.41%). Similar RRs were observed regarding BMI variability and per unit standard deviation (SD) increase in body weight variability. Comparable effects were seen in people with and without diabetes, in White Europeans and Asians. In conclusion, body weight variability is associated with increased risk of CV diseases regardless of ethnicity or diabetes status. Future research is needed to prove a causative link between weight variability and CVD risk, as appropriate interventions to maintain stable weight could positively influence CVD.</AbstractText><br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Jan 2023; 22:5</small></div>
Massey RJ, Siddiqui MK, Pearson ER, Dawed AY
Cardiovasc Diabetol: 09 Jan 2023; 22:5 | PMID: 36624453
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<div><h4>Impaired insulin-stimulated myocardial glucose metabolic rate is associated with reduced estimated myocardial energetic efficiency in subjects with different degrees of glucose tolerance.</h4><i>Succurro E, Cicone F, Papa A, Miceli S, ... Andreozzi F, Sesti G</i><br /><b>Background</b><br />Alterations in myocardial mechano-energetic efficiency (MEEi), which represents the capability of the left ventricles to convert the chemical energy obtained by oxidative metabolism into mechanical work, have been associated with cardiovascular disease. Although whole-body insulin resistance has been related to impaired myocardial MEEi, it is unknown the relationship between cardiac insulin resistance and MEEi. Aim of this study was to evaluate the relationship between insulin-stimulated myocardial glucose metabolic rate (MrGlu) and myocardial MEEi in subjects having different degrees of glucose tolerance.<br /><b>Methods</b><br />We evaluated insulin-stimulated myocardial MrGlu using cardiac dynamic positron emission tomography (PET) with <sup>18</sup>F-Fluorodeoxyglucose (<sup>18</sup>F-FDG) combined with euglycemic-hyperinsulinemic clamp, and myocardial MEEi in 57 individuals without history of coronary heart disease having different degrees of glucose tolerance. The subjects were stratified into tertiles according to their myocardial MrGlu values.<br /><b>Results</b><br />After adjusting for age, gender and BMI, subjects in I tertile showed a decrease in myocardial MEEi (0.31 ± 0.05 vs 0.42 ± 0.14 ml/s*g, P = 0.02), and an increase in myocardial oxygen consumption (MVO<sub>2</sub>) (10,153 ± 1375 vs 7816 ± 1229 mmHg*bpm, P < 0.0001) as compared with subjects in III tertile. Univariate correlations showed that insulin-stimulated myocardial MrGlu was positively correlated with MEEi and whole-body glucose disposal, and negatively correlated with waist circumference, fasting plasma glucose, HbA1c and MVO<sub>2</sub>. In a multivariate regression analysis running a model including several CV risk factors, the only variable that remained significantly associated with MEEi was myocardial MrGlu (β 0.346; P = 0.01).<br /><b>Conclusions</b><br />These data suggest that an impairment in insulin-stimulated myocardial glucose metabolism is an independent contributor of depressed myocardial MEEi in subjects without history of CHD.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Jan 2023; 22:4</small></div>
Succurro E, Cicone F, Papa A, Miceli S, ... Andreozzi F, Sesti G
Cardiovasc Diabetol: 09 Jan 2023; 22:4 | PMID: 36624469
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<div><h4>Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study.</h4><i>Lin SM, Liu PP, Tu YK, Lai EC, ... Huang HK, Loh CH</i><br /><b>Background</b><br />Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.<br /><b>Methods</b><br />A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.<br /><b>Results</b><br />The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.<br /><b>Conclusions</b><br />This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 06 Jan 2023; 22:1</small></div>
Lin SM, Liu PP, Tu YK, Lai EC, ... Huang HK, Loh CH
Cardiovasc Diabetol: 06 Jan 2023; 22:1 | PMID: 36609317
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<div><h4>The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis.</h4><i>Yang Y, Huang X, Wang Y, Leng L, ... Wang Y, Chen L</i><br /><b>Background</b><br />Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes.<br /><b>Methods</b><br />The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on \'\'TyG index\'\' and \"stroke\" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0.<br /><b>Results</b><br />A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22-1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I<sup>2</sup> = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19-1.89) and increased risk of mortality (OR 1.40 95% CI 1.14-1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88-1.43) and neurological worsening (OR: 1.76; 95% CI 0.79-3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I<sup>2</sup> = 77.20%).<br /><b>Conclusions</b><br />TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.<br /><br />© 2023. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 06 Jan 2023; 22:2</small></div>
Yang Y, Huang X, Wang Y, Leng L, ... Wang Y, Chen L
Cardiovasc Diabetol: 06 Jan 2023; 22:2 | PMID: 36609319
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<div><h4>High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank.</h4><i>Jin Q, Lau ESH, Luk AO, Tam CHT, ... Ma RCW, Hong Kong Diabetes Biobank Study Group</i><br /><b>Objective</b><br />High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility.<br /><b>Research design and methods</b><br />HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value.<br /><b>Results</b><br />Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model.<br /><b>Conclusion</b><br />Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 31 Dec 2022; 21:293</small></div>
Jin Q, Lau ESH, Luk AO, Tam CHT, ... Ma RCW, Hong Kong Diabetes Biobank Study Group
Cardiovasc Diabetol: 31 Dec 2022; 21:293 | PMID: 36587202
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<div><h4>Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients.</h4><i>Charpentier E, Redheuil A, Bourron O, Boussouar S, ... Phan F, COVID-19 APHP. SU Group</i><br /><b>Background</b><br />Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D.<br /><b>Methods</b><br />Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined.<br /><b>Results</b><br />One hundred and eight controls [median age: 76(IQR:59-83), 61% male, median BMI: 24(22-27)] and ninety-four T2D patients [median age: 70(IQR:61-77), 70% male, median BMI: 27(24-31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was  > 100 mL/m<sup>2</sup> with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death.<br /><b>Conclusions</b><br />Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 31 Dec 2022; 21:294</small></div>
Charpentier E, Redheuil A, Bourron O, Boussouar S, ... Phan F, COVID-19 APHP. SU Group
Cardiovasc Diabetol: 31 Dec 2022; 21:294 | PMID: 36587209
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<div><h4>In-hospital glycemic variability and all-cause mortality among patients hospitalized for acute heart failure.</h4><i>Chun KH, Oh J, Lee CJ, Park JJ, ... Oh BH, Kang SM</i><br /><b>Background</b><br />High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF).<br /><b>Methods</b><br />The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge.<br /><b>Results</b><br />The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan-Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P < 0.001). Multivariate Cox proportional analysis showed that high GV was associated with an increased risk of 1-year (HR 1.56, 95% CI 1.26-1.92) mortality. High GV significantly increased the risk of 1-year mortality in non-diabetic patients (HR 1.93, 95% CI 1.47-2.54) but not in diabetic patients (HR 1.19, 95% CI 0.86-1.65, P for interaction = 0.021).<br /><b>Conclusions</b><br />High in-hospital GV before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic patients with acute HF.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 27 Dec 2022; 21:291</small></div>
Chun KH, Oh J, Lee CJ, Park JJ, ... Oh BH, Kang SM
Cardiovasc Diabetol: 27 Dec 2022; 21:291 | PMID: 36575485
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<div><h4>\'Stress hyperglycemia ratio and in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.</h4><i>Zhou Y, Liu L, Huang H, Li N, ... Li S, WECODe Study Group</i><br /><b>Objective</b><br />To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.<br /><b>Research design and methods</b><br />We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection.<br /><b>Results</b><br />Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection.<br /><b>Conclusions</b><br />Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 26 Dec 2022; 21:290</small></div>
Zhou Y, Liu L, Huang H, Li N, ... Li S, WECODe Study Group
Cardiovasc Diabetol: 26 Dec 2022; 21:290 | PMID: 36572923
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<div><h4>Insulin resistance mediates obesity-related risk of cardiovascular disease: a prospective cohort study.</h4><i>Tian X, Chen S, Wang P, Xu Q, ... Wu S, Wang A</i><br /><b>Background</b><br />The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the insulin resistance seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity on cardiovascular disease (CVD) is mediated by insulin resistance.<br /><b>Methods</b><br />A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. Insulin resistance was evaluated by the triglyceride-glucose (TyG) index, calculating as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Mediation analysis using a new 2-stage regression method for survival data proposed by Valeri and VanderWeele was to explore the mediating effects of the TyG index on the association between obesity and CVD.<br /><b>Results</b><br />During a median follow-up of 13.01 years, we identified 7327 cases of CVD. Mediation analyses showed that 47.81% of the total association (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.12-1.24) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.07; 95% CI, 1.07-1.09), and the proportion mediated was 37.94% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 32.01, 35.02, and 31.06% for obesity, taken normal weight as reference.<br /><b>Conclusions</b><br />The association between obesity and CVD was mediated by TyG index, suggesting proper control of insulin resistance can be effective to reduce the effects of obesity on CVD.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Dec 2022; 21:289</small></div>
Tian X, Chen S, Wang P, Xu Q, ... Wu S, Wang A
Cardiovasc Diabetol: 23 Dec 2022; 21:289 | PMID: 36564775
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<div><h4>The associations between changes in hepatic steatosis and heart failure and mortality: a nationwide cohort study.</h4><i>Park J, Kim G, Kim H, Lee J, Jin SM, Kim JH</i><br /><b>Background</b><br />Non-alcoholic fatty liver disease (NAFLD) is a well-known risk factor for cardiovascular (CV) disease (CVD) and mortality. However, whether the progression or regression of NAFLD can increase or decrease the risk of heart failure (HF) and mortality has not been fully evaluated. We investigated the association between changes in hepatic steatosis and the risks of incident HF (iHF), hospitalization for HF (hHF), and mortality including CV- or liver-related mortality.<br /><b>Methods</b><br />Using a database from the National Health Insurance Service in Korea from January 2009 to December 2012, we analyzed 240,301 individuals who underwent health check-ups at least twice in two years. Hepatic steatosis was assessed using the fatty liver index (FLI), with an FLI ≥ 60 considered to indicate the presence of hepatic steatosis. According to FLI changes, participants were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models.<br /><b>Results</b><br />Persistent hepatic steatosis increased the risk of iHF, hHF, and mortality including CV- and liver-related mortality compared with the group that never had steatosis (all P < 0.05). Incident hepatic steatosis was associated with increased risk for iHF and mortality including CV- or liver-related mortality (all P < 0.05). Compared with persistent steatosis, regression of hepatic steatosis was associated with decreased risk for iHF, hHF, and liver-related mortality (iHF, HR [95% CI], 0.800 [0.691-0.925]; hHF, 0.645 [0.514-0.810]; liver-related mortality, 0.434 [0.223-0.846]).<br /><b>Conclusions</b><br />FLI changes were associated with increased or decreased risk of HF outcomes and mortality.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Dec 2022; 21:287</small></div>
Park J, Kim G, Kim H, Lee J, Jin SM, Kim JH
Cardiovasc Diabetol: 23 Dec 2022; 21:287 | PMID: 36564787
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<div><h4>Machine learning of plasma metabolome identifies biomarker panels for metabolic syndrome: findings from the China Suboptimal Health Cohort.</h4><i>Wang H, Wang Y, Li X, Deng X, ... Wang W, Zhou Y</i><br /><b>Background</b><br />Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising \"omics\" technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods.<br /><b>Methods</b><br />Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers for MetS. Metabolic pathway enrichment analysis was performed to reveal the disturbed metabolic pathways related to MetS. Four machine learning algorithms, including support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), and logistic regression were used to build diagnostic models for MetS.<br /><b>Results</b><br />Thirteen significantly differential metabolites were identified and pathway enrichment revealed that arginine, proline, and glutathione metabolism are disturbed metabolic pathways related to MetS. The protein-metabolite-disease interaction network identified 38 proteins and 23 diseases are associated with 10 MetS-related metabolites. The areas under the receiver operating characteristic curve of the SVM, RF, KNN, and logistic regression models based on metabolic biomarkers were 0.887, 0.993, 0.914, and 0.755, respectively.<br /><b>Conclusions</b><br />The plasma metabolome provides a promising resource of biomarkers for the predictive diagnosis and targeted prevention of MetS. Alterations in amino acid metabolism play significant roles in the pathophysiology of MetS. The biomarker panels and metabolic pathways could be used as preventive targets in dealing with cardiometabolic diseases related to MetS.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Dec 2022; 21:288</small></div>
Wang H, Wang Y, Li X, Deng X, ... Wang W, Zhou Y
Cardiovasc Diabetol: 23 Dec 2022; 21:288 | PMID: 36564831
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<div><h4>Effects of single and multiple sessions of lower body diastole-synchronized compressions using a pulsating pneumatic suit on endothelium function and metabolic parameters in patients with type 2 diabetes: two controlled cross-over studies.</h4><i>Valensi P, Barber-Chamoux N, Rezki A, Lambert C, ... Delmas D, Duclos M</i><br /><b>Background</b><br />Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes.<br /><b>Methods</b><br />Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4-6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months.<br /><b>Results</b><br />Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions.<br /><b>Conclusions</b><br />Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 22 Dec 2022; 21:286</small></div>
Abstract
<div><h4>Elevated circulating level of β-aminoisobutyric acid (BAIBA) in heart failure patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitors.</h4><i>Katano S, Yano T, Kouzu H, Nagaoka R, ... Kuno A, Furuhashi M</i><br /><b>Aims</b><br />The mechanism by which a sodium-glucose cotransporter inhibitor (SGLT2i) induces favorable effects on diabetes and cardiovascular diseases including heart failure (HF) remains poorly understood. Metabolomics including amino acid profiling enables detection of alterations in whole body metabolism. The aim of this study was to determine whether plasma amino acid profiles are modulated by SGLT2i use in HF patients with type 2 diabetes mellitus (T2DM).<br /><b>Methods</b><br />We retrospectively examined 81 HF patients with T2DM (68 ± 11 years old; 78% male). Plasma amino acid concentrations in a fasting state after stabilization of HF were determined using ultraperformance liquid chromatography. To minimize potential selection bias in the retrospective analyses, the differences in baseline characteristics between patients receiving an SGLT2i and patients not receiving an SGLT2i were controlled by using an inverse probability of treatment weighting (IPTW)-adjusted analysis.<br /><b>Results</b><br />Of amino acids measurable in the present assay, plasma β-aminoisobutyric acid (BAIBA), an exercise-induced myokine-like molecule also known as 3-aminoisobutyric acid or 3-amino-2-methyproponic acid, was detected in 77% of all patients and the proportion of patients in whom plasma BAIBA was detected was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i (93% vs. 67%, p = 0.01). Analyses in patients in whom plasma BAIBA was detected showed that plasma BAIBA concentration was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i (6.76 ± 4.72 vs. 4.56 ± 2.93 nmol/ml, p = 0.03). In multivariate logistic regression analyses that were adjusted for age and sex, SGLT2i use was independently associated with BAIBA detection. The independent association between BAIBA and SGLT2i use remained after inclusion of body mass index, HF with reduced ejection fraction, ischemic etiology, renal function, NT-proBNP, albumin, hemoglobin, and HbA1c into the Cox proportional hazards model. When the differences in baseline characteristics between patients receiving an SGLT2i and patients not receiving an SGLT2i were controlled by using an IPTW-adjusted analysis, least squares mean of plasma BAIBA concentration was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i.<br /><b>Conclusion</b><br />SGLT2i use is closely associated with increased circulating BAIBA concentration in HF patients with T2DM.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 20 Dec 2022; 21:285</small></div>
Katano S, Yano T, Kouzu H, Nagaoka R, ... Kuno A, Furuhashi M
Cardiovasc Diabetol: 20 Dec 2022; 21:285 | PMID: 36539818
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<div><h4>Insulin resistance phenotype is associated with vascular risk phenotype at the end of the second decade of life: a population-based study.</h4><i>Barbosa JMA, da Silva AAM, Batista RFL, Salgado BJL, ... Ferraro AA, Ribeiro CCC</i><br /><AbstractText>We hypothesize that early events of diabetes and cardiovascular disease continuums would be ongoing and associated in adolescents. We investigated the association between the Insulin Resistance Phenotype and the Vascular Risk Phenotype at the end of the second decade of life and indirect pathways from social vulnerability, alcohol consumption, and body fat mass. It is a population-based study in the RPS cohort of 18-19 years (n = 2,515), São Luís, Brazil. The theoretical model analyzed the association between Insulin Resistance Phenotype and Vascular Risk Phenotype by sex, using structural equation modeling (SEM). The Insulin Resistance Phenotype was a latent variable deduced from the correlations of Triglyceride to HDL ratio, Triglyceride Glycemic index, and VLDL; the Vascular Risk Phenotype was deduced from Systolic Blood Pressure, Diastolic Blood Pressure, and Pulse Wave Velocity. The Insulin Resistance Phenotype was directly associated with the Vascular Risk Phenotype in males (standardized coefficient SC = 0.183; p < 0.001) and females (SC = 0.152; p < 0.001). The Insulin Resistance Phenotype was an indirect pathway in the association of alcohol consumption and higher values of fat mass index with the Vascular Risk Phenotype. VLDL presented the highest factor loading, appearing as a marker of insulin resistance linked to cardiovascular risk in young people. Lower values of socioeconomic status, harmful use of alcohol, and high body fat values were also associated with higher values of the two phenotypes. The association of the Insulin Resistance Phenotype with the Vascular Risk Phenotype suggests common pathophysiological mechanisms present in early events in the continuums of diabetes and cardiovascular disease in adolescence.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 19 Dec 2022; 21:284</small></div>
Barbosa JMA, da Silva AAM, Batista RFL, Salgado BJL, ... Ferraro AA, Ribeiro CCC
Cardiovasc Diabetol: 19 Dec 2022; 21:284 | PMID: 36536371
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<div><h4>Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level.</h4><i>Xia Z, Song L, Fang D, You W, ... Jiang J, He Y</i><br /><b>Background</b><br />Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels.<br /><b>Methods</b><br />This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function.<br /><b>Results</b><br />After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053-0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was \"paradoxically\" associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = - 0.043, 95%CI - 0.067 to - 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%.<br /><b>Conclusions</b><br />In early stage of diabetes, a slightly elevated SBP (140-150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 19 Dec 2022; 21:283</small></div>
Xia Z, Song L, Fang D, You W, ... Jiang J, He Y
Cardiovasc Diabetol: 19 Dec 2022; 21:283 | PMID: 36536433
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<div><h4>Patients with type 1 and type 2 diabetes hospitalized with COVID-19 in comparison with influenza: mortality and cardiorenal complications assessed by nationwide Swedish registry data.</h4><i>Kristófi R, Bodegard J, Ritsinger V, Thuresson M, ... Norhammar A, Eriksson JW</i><br /><b>Background</b><br />The risk of severe coronavirus disease 2019 (COVID-19) is increased in people with diabetes, but effects of diabetes type and other risk factors remain incompletely characterized. We studied this in a Swedish cohort of hospitalized patients with type 1 and type 2 diabetes (T1D and T2D), also including comparisons with influenza epidemics of recent years.<br /><b>Methods</b><br />Nationwide healthcare registries were used to identify patients. A total of 11,005 adult patients with diabetes (T1D, n = 373; T2D, n = 10,632) were hospitalized due to COVID-19 from January 1, 2020 to September 1, 2021. Moreover, 5111 patients with diabetes (304 T1D, 4807 T2D) were hospitalized due to influenza from January 1, 2015 to December 31, 2019. Main outcomes were death within 28 days after admission and new hospitalizations for heart failure (HF), chronic kidney disease (CKD), cardiorenal disease (CRD; composite of HF and CKD), myocardial infarction (MI) and stroke during 1 year of follow-up.<br /><b>Results</b><br />Number of deaths and CRD events were 2025 and 442 with COVID-19 and 259 and 525 with influenza, respectively. Age- and sex-adjusted Cox regression models in COVID-19 showed higher risk of death and HF in T1D vs. T2D, hazard ratio (HR) 1.77 (95% confidence interval 1.41-2.22) and 2.57 (1.31-5.05). With influenza, T1D was associated with higher risk of death compared with T2D, HR 1.80 (1.26-2.57). Older age and previous CRD were associated with higher risks of death and hospitalization for CRD. After adjustment for prior comorbidities, mortality differences were still significant, but there were no significant differences in cardiovascular and renal outcomes. COVID-19 relative to influenza was associated with higher risk of death in both T1D and T2D, HR 2.44 (1.60-3.72) and 2.81 (2.59-3.06), respectively.<br /><b>Conclusions</b><br />In Sweden, patients with T1D as compared to T2D had a higher age- and sex-adjusted risk of death within 28 days and HF within one year after COVID-19 hospitalization, whereas the risks of other non-fatal cardiovascular and renal disease events were similar. Patients with T1D as well as T2D have a greater mortality rate when hospitalized due to COVID-19 compared to influenza, underscoring the importance of vaccination and other preventive measures against COVID-19 for diabetes patients.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 15 Dec 2022; 21:282</small></div>
Kristófi R, Bodegard J, Ritsinger V, Thuresson M, ... Norhammar A, Eriksson JW
Cardiovasc Diabetol: 15 Dec 2022; 21:282 | PMID: 36522650
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<div><h4>The association between time in the glucose target range and abnormal ankle-brachial index: a cross-sectional analysis.</h4><i>Wei Y, Liu C, Liu Y, Zhang Z, ... Gu P, Shao J</i><br /><b>Background</b><br />Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes.<br /><b>Methods</b><br />We retrospectively collected patients\' information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9-10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI.<br /><b>Results</b><br />The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups.<br /><b>Conclusions</b><br />In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 13 Dec 2022; 21:281</small></div>
Wei Y, Liu C, Liu Y, Zhang Z, ... Gu P, Shao J
Cardiovasc Diabetol: 13 Dec 2022; 21:281 | PMID: 36514151
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<div><h4>Predictive effect of triglyceride-glucose index on clinical events in patients with acute ischemic stroke and type 2 diabetes mellitus.</h4><i>Liu D, Yang K, Gu H, Li Z, Wang Y, Wang Y</i><br /><b>Background</b><br />The triglyceride-glucose (TyG) index was significantly related to clinical outcome in patients with cardiovascular disease (CAD) and cerebrovascular disease (CVD). We aim to investigate the association between TyG index and clinical prognosis of acute ischemic stroke (IS) patients with type-2 diabetes mellitus (T2DM).<br /><b>Methods</b><br />Among 19,604 patients with acute IS admitted to the China National Stroke Registry II (CNSRII), 3359 IS patients with T2DM were included in the cross-sectional analysis. The TyG index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into four quartiles. The outcomes included recurrent IS, all-cause death and poor outcome at 1 year were analyzed. The association between the TyG index and adverse cerebrovascular outcomes was assessed by proportional hazards regression analysis.<br /><b>Results</b><br />During 1 year follow-up, recurrent IS, all-cause death and poor outcome occurred in 305 (9.08%), 229 (6.82%) and 443 (47.9%) cases, respectively. Multivariable Cox proportional hazards analyses showed that the risk of incident primary endpoints was associated with a higher TyG quartile. After adjustment for confounding factors, patients with a higher TyG index had an association with IS recurrence (adjusted hazard ratio, 1.41; 95% confidence interval, 0.97-2.03; P = 0.048) and all-cause death (adjusted hazard ratio, 1.70; 95% confidence interval, 1.062-2.74; P = 0.028), compared with those in the first quartile at 1 year time follow-up. In addition, there were interactions between TyG index and age (≥ 65), female, hypertensive agents, anticoagulant agents, statins and antidiabetic agents in subgroup analyses, especially patients without taken anticoagulant drugs were significantly related to IS recurrence, all-cause death and poor outcome (P = 0.003, P = 0.006 and P = 0.001, respectively).<br /><b>Conclusions</b><br />TyG index is strongly related to the IS recurrence and all-cause death in acute IS patients with T2DM. This finding indicates that the TyG index might be a potential predictor of clinical outcome for acute IS patients with T2DM.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Dec 2022; 21:280</small></div>
Liu D, Yang K, Gu H, Li Z, Wang Y, Wang Y
Cardiovasc Diabetol: 12 Dec 2022; 21:280 | PMID: 36510223
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<div><h4>Gender disparities in time-to-initiation of cardioprotective glucose-lowering drugs in patients with type 2 diabetes and cardiovascular disease: a Danish nationwide cohort study.</h4><i>Funck KL, Bjerg L, Isaksen AA, Sandbæk A, Grove EL</i><br /><b>Background</b><br />We aimed to examine the impact of gender and specific type of cardiovascular disease (CVD) diagnosis (ischemic heart disease [IHD], heart failure, peripheral artery disease [PAD] or stroke) on time-to-initiation of either a sodium glucose cotransporter 2 inhibitor or glucagon-like peptide 1 analogue (collectively termed cardioprotective GLD) after a dual diagnosis of type 2 diabetes (T2DM) and CVD.<br /><b>Methods</b><br />In a nationwide cohort study, we identified patients with a new dual diagnosis of T2DM and CVD (January 1, 2012 and December 31, 2018). Cumulative user proportion (CUP) were assessed. Poisson models were used to estimate the initiation rate of cardioprotective GLDs. The final analyses were adjusted for potential confounders.<br /><b>Results</b><br />In total, we included 70,538 patients with new-onset T2DM and CVD (38% female, mean age 70 ± 12 years at inclusion). During 183,256 person-years, 6,276 patients redeemed a prescription of a cardioprotective GLD. One-year CUPs of cardioprotective GLDs were lower in women than men. Initiation rates of GLDs were lower in women (female-to-male initiation-rate-ratio crude: 0.76, 95% CI 0.72-0.81); adjusted 0.92, 95% CI 0.87-0.97). In CVD-stratified analysis, the adjusted initiation rate ratio was lower in female patients with IHD and heart failure (IHD: 0.91 [95% CI 0.85-0.98], heart failure: 0.85 [95% CI 0.73-1.00], PAD: 0.92 [95% CI 0.78-1.09], and stroke: 1.06 [95% CI 0.93-1.20]).<br /><b>Conclusions</b><br />Among patients with a new dual diagnosis of T2DM and CVD, female gender is associated with lower initiation rates of cardioprotective GLDs, especially if the patient has IHD or heart failure.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 10 Dec 2022; 21:279</small></div>
Abstract
<div><h4>Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.</h4><i>Cheon DY, Han K, Yang YS, Kim Y, ... Lee M, Yu KH</i><br /><b>Background</b><br />Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes.<br /><b>Research design and methods</b><br />A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status.<br /><b>Results</b><br />Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age.<br /><b>Conclusions</b><br />In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Dec 2022; 21:275</small></div>
Cheon DY, Han K, Yang YS, Kim Y, ... Lee M, Yu KH
Cardiovasc Diabetol: 09 Dec 2022; 21:275 | PMID: 36494651
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<div><h4>Association of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.</h4><i>Halabi A, Potter E, Yang H, Wright L, ... Shaw JE, Marwick TH</i><br /><b>Background</b><br />Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography.<br /><b>Methods</b><br />Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e\' ≥ 14 or e\' < 8 cm/s), left atrial volume index (LAV > 34 ml/m<sup>2</sup>) and LV hypertrophy (LV mass index > 88 g/m<sup>2</sup> (F) > 102 g/m<sup>2</sup>(M)).<br /><b>Results</b><br />Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e\' in 114 (15%), impaired e\' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised β = 0.22, p < 0.001) and WATCH-DM (standardised β = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e\' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity.<br /><b>Conclusion</b><br />Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Dec 2022; 21:278</small></div>
Halabi A, Potter E, Yang H, Wright L, ... Shaw JE, Marwick TH
Cardiovasc Diabetol: 09 Dec 2022; 21:278 | PMID: 36494683
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<div><h4>Time-varying parameters of glycemic control and glycation in relation to arterial stiffness in patients with type 1 diabetes.</h4><i>Helleputte S, Calders P, Rodenbach A, Marlier J, ... De Backer T, Lapauw B</i><br /><b>Background</b><br />A substantial proportion of type 1 diabetes (T1D) patients free from known cardiovascular disease (CVD) show premature arterial stiffening, with age, blood pressure, and HbA1c-as gold standard of glycemic control-as main predictors. However, the relationship of arterial stiffness with other time-varying parameters of glycemic control and glycation has been far less explored. This study investigated the relationship of arterial stiffness with several short- and long-term parameters of glycemic control and glycation in patients with T1D, such as advanced glycation end-products (AGEs) and continuous glucose monitoring (CGM)-derived parameters.<br /><b>Methods</b><br />Cross-sectional study at a tertiary care centre including 54 patients with T1D free from known CVD. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV). Current level and 10-year history of HbA1c were evaluated, and skin AGEs, urinary AGEs, and serum soluble AGE-receptor (sRAGE) concentrations. CGM for 7 days was used to determine time in range, time in hyper- and hypoglycemia, and glycemic variability.<br /><b>Results</b><br />Cf-PWV was associated with current HbA1c (r<sub>s</sub> = + 0.28), mean 10-years HbA1c (r<sub>s</sub> = + 0.36), skin AGEs (r<sub>s</sub> = + 0.40) and the skin AGEs-to-sRAGE ratio (r<sub>s</sub> = + 0.40), but not with urinary AGE or serum sRAGE concentrations; and not with any of the CGM-parameters. Multiple linear regression for cf-PWV showed that the model with the best fit included age, T1D duration, 24-h mean arterial pressure and mean 10-years HbA1c (adjusted R<sup>2</sup> = 0.645, p < 0.001).<br /><b>Conclusions</b><br />Longer-term glycemic exposure as reflected by current and mean 10-years HbA1c is a key predictor of arterial stiffness in patients with T1D, while no relationship was found with any of the short-term CGM parameters. Our findings stress the importance of early and sustained good glycemic control to prevent premature CVD in patients with T1D and suggest that HbA1c should continue to be used in the risk assessment for diabetic complications. The role of skin glycation, as a biomarker for vascular aging, in the risk assessment for CVD is an interesting avenue for further research.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Dec 2022; 21:277</small></div>
Helleputte S, Calders P, Rodenbach A, Marlier J, ... De Backer T, Lapauw B
Cardiovasc Diabetol: 09 Dec 2022; 21:277 | PMID: 36494687
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<div><h4>Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture.</h4><i>Xiao H, Ma Y, Zhou Z, Li X, ... Wu T, Chen D</i><br /><b>Background</b><br />Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D.<br /><b>Method</b><br />A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets.<br /><b>Results</b><br />We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy).<br /><b>Conclusion</b><br />The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Dec 2022; 21:276</small></div>
Xiao H, Ma Y, Zhou Z, Li X, ... Wu T, Chen D
Cardiovasc Diabetol: 09 Dec 2022; 21:276 | PMID: 36494812
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<div><h4>Management of type 2 diabetes with a treat-to-benefit approach improved long-term cardiovascular outcomes under routine care.</h4><i>Morieri ML, Longato E, Di Camillo B, Sparacino G, Avogaro A, Fadini GP</i><br /><b>Background</b><br />Results of cardiovascular outcome trials enabled a shift from \"treat-to-target\" to \"treat-to-benefit\" paradigm in the management of type 2 diabetes (T2D). However, studies validating such approach are limited. Here, we examined whether treatment according to international recommendations for the pharmacological management of T2D had an impact on long-term outcomes.<br /><b>Methods</b><br />This was an observational study conducted on outpatient data collected in 2008-2018 (i.e. prior to the \"treat-to-benefit\" shift). We defined 6 domains of treatment based on the ADA/EASD consensus covering all disease stages: first- and second-line treatment, intensification, use of insulin, cardioprotective, and weight-affecting drugs. At each visit, patients were included in Group 1 if at least one domain deviated from recommendation or in Group 2 if aligned with recommendations. We used Cox proportional hazard models with time-dependent co-variates or Cox marginal structural models (with inverse-probability of treatment weighing evaluated at each visit) to adjust for confounding factors and evaluate three outcomes: major adverse cardiovascular events (MACE), hospitalization for heart failure or cardiovascular mortality (HF-CVM), and all-cause mortality.<br /><b>Results</b><br />We included 5419 patients, on average 66-year old, 41% women, with a baseline diabetes duration of 7.6 years. Only 11.7% had pre-existing cardiovascular disease. During a median follow-up of 7.3 years, patients were seen 12 times at the clinic, and we recorded 1325 MACE, 1593 HF-CVM, and 917 deaths. By the end of the study, each patient spent on average 63.6% of time in Group 1. In the fully adjusted model, being always in Group 2 was associated with a 45% lower risk of MACE (HR 0.55; 95% C.I. 0.46-0.66; p < 0.0001) as compared to being in Group 1. The corresponding HF-CVM and mortality risk were similar (HR 0.56; 95%CI 0.47-0.66, p < 0.0001 and HR 0.56; 95% C.I. 0.45-0.70; p < 0.0001. respectively). Sensitivity analyses confirmed these results. No single domain individually explained the better outcome of Group 2, which remained significant in all subgroups.<br /><b>Conclusion</b><br />Managing patients with T2D according to a \"treat-to-benefit\" approach based international standards was associated with a lower risk of MACE, heart failure, and mortality. These data provide ex-post validation of the ADA/EASD treatment algorithm.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Dec 2022; 21:274</small></div>
Morieri ML, Longato E, Di Camillo B, Sparacino G, Avogaro A, Fadini GP
Cardiovasc Diabetol: 09 Dec 2022; 21:274 | PMID: 36494815
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<div><h4>The association of fatty liver index and BARD score with all-cause and cause-specific mortality in patients with type 2 diabetes mellitus: a nationwide population-based study.</h4><i>Chung GE, Jeong SM, Cho EJ, Yoon JW, ... Han K, Yu SJ</i><br /><b>Background</b><br />Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD\'s effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes.<br /><b>Methods</b><br />We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score.<br /><b>Findings</b><br />During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01-1.03 for all-cause; 1.07, 1.04-1.10 for CVD; 1.12, 1.09-1.14 for cancer; and 2.63, 2.50-2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10-1.12), CVD- (HR, 95% CI 1.11, 1.09-1.14), cancer- (HR, 95% CI 1.17, 1.15-1.19), and liver disease-related (HR, 95% CI 2.38, 2.29-2.49) mortality.<br /><b>Conclusion</b><br />Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 06 Dec 2022; 21:273</small></div>
Chung GE, Jeong SM, Cho EJ, Yoon JW, ... Han K, Yu SJ
Cardiovasc Diabetol: 06 Dec 2022; 21:273 | PMID: 36474232
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<div><h4>Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review.</h4><i>Rouland A, Masson D, Lagrost L, Vergès B, Gautier T, Bouillet B</i><br /><AbstractText>Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 05 Dec 2022; 21:272</small></div>
Rouland A, Masson D, Lagrost L, Vergès B, Gautier T, Bouillet B
Cardiovasc Diabetol: 05 Dec 2022; 21:272 | PMID: 36471375
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<div><h4>Benefits of successful percutaneous coronary intervention in chronic total occlusion patients with diabetes.</h4><i>Zhao S, Chen Y, Wang Q, Zhu B, ... Li C, Lian K</i><br /><b>Background</b><br />Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes.<br /><b>Methods</b><br />Consecutive patients undergoing elective CTO-PCI were prospectively enrolled from Apr. 2018 to May 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. These data were analyzed accordingly for risk predictors of clinical outcome in patients who have diabetes and received successful CTO-PCI.<br /><b>Results</b><br />A total of 1076 patients underwent CTO-PCI attempts. Diabetes was present in 374 (34.76%) patients, who had more hypertension, previous PCI and stroke. Regarding the coronary lesions, diabetic patients suffered more LCX lesion, multivessel disease, number of lesions per patient, blunt stump, calcification and higher J-CTO score (p < 0.05). In-hospital major adverse cardiac event (MACE) (4.13% vs. 5.35%; p = 0.362) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, the incidence of MACE and all-cause mortality were also similar in the two groups (p > 0.05). Number of lesions per patient was an independent risk factor of MACE and all-cause mortality (p < 0.001) 1 year after successful CTO-PCI. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, patients with diabetes showed similar degrees of improvement to those without diabetes (P > 0.05).<br /><b>Conclusions</b><br />Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptoms and QOL in CTO patients with diabetes.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 05 Dec 2022; 21:271</small></div>
Zhao S, Chen Y, Wang Q, Zhu B, ... Li C, Lian K
Cardiovasc Diabetol: 05 Dec 2022; 21:271 | PMID: 36471410
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<div><h4>Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis.</h4><i>Kohansal K, Masrouri S, Khalili D, Ramezankhani A, ... Blaha MJ, Hadaegh F</i><br /><b>Background</b><br />We aimed to assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes (T2DM) during an 18-year follow-up.<br /><b>Methods</b><br />The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: (1) normal FPG (NFG) to NFG (reference category); (2) NFG to impaired fasting glucose (IFG) (i.e., 126 > FPG ≥ 100 mg/dl); (3) NFG to T2DM; (4) IFG to NFG; (5) IFG to IFG; (6) IFG to T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia was used to estimate hazard ratios (HRs (95% CI)) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated.<br /><b>Results</b><br />During follow-up, 2,362 all-cause mortality events were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95%CI 1.24 (0.98-1.57), p = 0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM group were at increased risk for CV mortality (2.21 (1.42-3.44)). We also found that women in NFG-IFG (1.52 (1.20-1.91)), NFG-T2DM (2.90 (1.52-5.51)), and IFG-IFG (1.30 (1.02-1.66)) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 (1.15-2.74)) and IFG-T2DM (1.34 (1.04-1.72)). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts (RHR; 1.24 (1.01-1.54)). After further adjustment for physical activity, results were in line with the main findings, excluding T2DM up to six years after the measurement period and early mortality events.<br /><b>Conclusion</b><br />In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 03 Dec 2022; 21:267</small></div>
Kohansal K, Masrouri S, Khalili D, Ramezankhani A, ... Blaha MJ, Hadaegh F
Cardiovasc Diabetol: 03 Dec 2022; 21:267 | PMID: 36463152
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<div><h4>The clinical value of metabolic syndrome and its components with respect to sudden cardiac death using different definitions: Two decades of follow-up from the Tehran Lipid and Glucose Study.</h4><i>Masrouri S, Moazzeni SS, Cheraghloo N, Azizi F, Hadaegh F</i><br /><b>Background</b><br />To evaluate the impact of different definitions of metabolic syndrome (MetS) and their components on the risk of sudden cardiac death (SCD) among the Iranian population according to the World Health Organization (WHO), International Diabetes Federation (IDF), Adult Treatment Panel III (ATP III), and Joint Interim Statement (JIS) criteria.<br /><b>Methods</b><br />The study population included a total of 5,079 participants (2,785 women) aged ≥ 40 years, free of cardiovascular disease (CVD) at baseline. Participants were followed for incident SCD annually up to 20 March 2018. Multivariable Cox proportional hazards regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MetS and its components for incident SCD.<br /><b>Results</b><br />The prevalence of MetS ranged from 27.16% to 50.81%, depending on the criteria used. Over a median of 17.9 years of follow-up, 182 SCD events occurred. The WHO, IDF, and JIS definitions were strong predictors of SCD with multivariable-adjusted HRs (95% CI) of 1.68 (1.20-2.35), 1.51 (1.12-2.03), and 1.47 (1.08-1.98), respectively; these associations significantly attenuated after further adjustment for MetS components. MetS by the ATP III definition was not associated with the risk of SCD after controlling for antihypertensive, glucose-lowering, and lipid-lowering medication use. Among the components of MetS, high blood pressure (WHO definition), high waist circumference (using the national cutoff of ≥ 95 cm), and high glucose component by the JIS/IDF definitions remained independent predictors of SCD with HRs of 1.79 (1.29-2.48), 1.46 (1.07-2.00), and 1.52 (1.12-2.05), respectively.<br /><b>Conclusions</b><br />The constellation of MetS, except for when defined with ATP III definition, is a marker for identifying individuals at higher risk for SCD; however, not independent of its components. Among MetS components, abdominal obesity using the population-specific cutoff point, high glucose component (JIS/IDF definitions), and high blood pressure (WHO definition) were independent predictors of SCD.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 03 Dec 2022; 21:269</small></div>
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<div><h4>Metabolic dysfunction-associated fatty liver disease and implications for cardiovascular risk and disease prevention.</h4><i>Zhou XD, Cai J, Targher G, Byrne CD, ... Zheng MH, CHESS-MAFLD consortium</i><br /><AbstractText>The newly proposed term \"metabolic dysfunction-associated fatty liver disease\" (MAFLD) is replacing the old term \"non-alcoholic fatty liver disease\" (NAFLD) in many global regions, because it better reflects the pathophysiology and cardiometabolic implications of this common liver disease. The proposed change in terminology from NAFLD to MAFLD is not simply a single-letter change in an acronym, since MAFLD is defined by a set of specific and positive diagnostic criteria. In particular, the MAFLD definition specifically incorporates within the classification recognized cardiovascular risk factors. Although convincing evidence supports a significant association between both NAFLD and MAFLD, with increased risk of CVD morbidity and mortality, neither NAFLD nor MAFLD have received sufficient attention from the Cardiology community. In fact, there is a paucity of scientific guidelines focusing on this common and burdensome liver disease from cardiovascular professional societies. This Perspective article discusses the rationale and clinical relevance for Cardiologists of the newly proposed MAFLD definition.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 03 Dec 2022; 21:270</small></div>
Zhou XD, Cai J, Targher G, Byrne CD, ... Zheng MH, CHESS-MAFLD consortium
Cardiovasc Diabetol: 03 Dec 2022; 21:270 | PMID: 36463192
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<div><h4>Association of cumulative monocyte to high-density lipoprotein ratio with the risk of type 2 diabetes: a prospective cohort study.</h4><i>Wu D, Lan Y, Xu Y, Xu S, ... Wang W, Wu S</i><br /><b>Background</b><br />Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM.<br /><b>Methods</b><br />This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM.<br /><b>Results</b><br />Over a median follow-up period of 7.98 (IQR: 5.74-8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05‒1.25), 1.17 (1.07‒1.27), 1.38 (1.26‒1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4‒year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01‒1.29), 1.17 (1.04‒1.32), 1.40 (1.25‒1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28‒1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk.<br /><b>Conclusions</b><br />Cumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 03 Dec 2022; 21:268</small></div>
Wu D, Lan Y, Xu Y, Xu S, ... Wang W, Wu S
Cardiovasc Diabetol: 03 Dec 2022; 21:268 | PMID: 36463212
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<div><h4>The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy.</h4><i>Wang S, Deng Z, Zhang H, Zhang R, ... Jia W, Hu C</i><br /><b>Background</b><br />Dimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy.<br /><b>Methods</b><br />In stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform.<br /><b>Results</b><br />In stage 1, serum ADMA levels correlated with common Hp genotypes (β ± SE = - 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101-2.783), P = 0.018].<br /><b>Conclusion</b><br />Hp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 02 Dec 2022; 21:265</small></div>
Wang S, Deng Z, Zhang H, Zhang R, ... Jia W, Hu C
Cardiovasc Diabetol: 02 Dec 2022; 21:265 | PMID: 36461077
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<div><h4>Body mass index versus surrogate measures of central adiposity as independent predictors of mortality in type 2 diabetes.</h4><i>Orsi E, Solini A, Penno G, Bonora E, ... Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group</i><br /><b>Background</b><br />An \"obesity paradox\" for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes.<br /><b>Methods</b><br />The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006-2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), <br /><b>Results:</b><br/>Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193-2.505), P = 0.004), moderately obese (1.214 [1.058-1.392), P = 0.006) and severely obese (1.703 [1.402-2.068), P < 0.0001), lower in overweight (0.842 [0.775-0.915), P < 0.0001) and similar in mildly obese (0.950 [0.864-1.045), P = 0.292), compared to normal-weight individuals. When further adjusting for smoking, physical activity (PA), and comorbidities, risk was lower also in mildly obese versus normal-weight patients. The BMI-mortality relationship did not change after sequentially excluding ever smokers, individuals with comorbidities, and those died within two years from enrollment and when analyzing separately participants below and above the median age. Conversely, a paradox relationship was observed among inactive/moderately inactive, but not moderately/highly active patients. Mortality risk adjusted for age, gender, smoking, PA and comorbidities was significantly higher in the highest tertile of WC (1.279 [1.089-1.501], P = 0.003), WHtR (1.372 [1.165-1.615], P < 0.0001), and ABSI (1.263 [1.067-1.495], P = 0.007) versus the lowest tertile. However, risk was lower in the intermediate versus lowest tertile for WC (0.823 [0.693-0.979], P = 0.028), similar for WHtR, and higher, though not significantly, for ABSI.<br /><b>Conclusions</b><br />An \"overweight paradox\" remained after controlling for age, smoking, and comorbidities, arguing against a collider bias or reverse causation. However, it could be partly explained by confounding from PA level, possibly through its impact on lean mass and cardiorespiratory fitness. No obesity paradox was observed with WHtR and especially ABSI, which predicted mortality risk associated with central adiposity better than WC. Trial registration ClinicalTrials.gov, NCT00715481, 15 July, 2008.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 02 Dec 2022; 21:266</small></div>
Orsi E, Solini A, Penno G, Bonora E, ... Pugliese G, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
Cardiovasc Diabetol: 02 Dec 2022; 21:266 | PMID: 36461034
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<div><h4>Triglyceride-glucose index as a prognostic marker after ischemic stroke or transient ischemic attack: a prospective observational study.</h4><i>Hoshino T, Mizuno T, Ishizuka K, Takahashi S, ... Toi S, Kitagawa K</i><br /><b>Background</b><br />Triglyceride-glucose (TyG) index has been proposed as a simple and credible surrogate for insulin resistance and an independent predictor of cardiovascular outcomes. Due to lack of data on TyG index in stroke, we aimed to evaluate the predictive value of the index for recurrent vascular event risk among stroke patients.<br /><b>Methods</b><br />This was a prospective observational study, in which 866 patients (mean age, 70.1 years; male, 60.9%) with ischemic stroke (n = 781) or transient ischemic attack (n = 85) within 1 week of onset were consecutively enrolled and followed up for 1 year. The TyG index was calculated as ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Patients were divided into 3 groups according to the tertile of TyG index levels: tertile 1, < 8.48; tertile 2, 8.48-9.01; and tertile 3, > 9.01. The primary outcome was a composite of major adverse cardiovascular events (MACE), including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death.<br /><b>Results</b><br />The median TyG index was 8.74 (interquartile range, 8.34-9.16). Higher levels of TyG index were significantly associated with increased prevalence of ipsilateral extracranial carotid (P = 0.032) and intracranial (P = 0.003) atherosclerotic stenosis. There were significant differences in the MACE risk between the three groups (annual rate, 8.6%, 11.6%, and 17.3% in the tertile 1, tertile 2, tertile 3 groups, respectively; log-rank P = 0.005). After multivariable adjustments, the TyG index remains to be a significant predictor of MACE, with an adjusted hazard ratio for tertile 3 versus tertile 1 groups (95% confidence interval) of 2.01 (1.16-3.47). Similar results were also found for the risk of recurrent stroke.<br /><b>Conclusions</b><br />TyG index is associated with cervicocerebral atherosclerosis and the MACE risk after a stroke, suggesting the potential value of TyG index to optimize the risk stratification of stroke patients. Trial registration URL:  https://upload.umin.ac.jp . Unique identifier: UMIN000031913.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 30 Nov 2022; 21:264</small></div>
Hoshino T, Mizuno T, Ishizuka K, Takahashi S, ... Toi S, Kitagawa K
Cardiovasc Diabetol: 30 Nov 2022; 21:264 | PMID: 36451149
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<div><h4>Unsupervised machine learning based on clinical factors for the detection of coronary artery atherosclerosis in type 2 diabetes mellitus.</h4><i>Jiang Y, Yang ZG, Wang J, Shi R, ... Yan WF, Li Y</i><br /><b>Background</b><br />Coronary atherosclerosis can lead to serious cardiovascular events. In type 2 diabetes (T2DM) patients, the effects of clinical factors on coronary atherosclerosis have not been fully elucidated. We used a clustering method to distinguish the population heterogeneity of T2DM and the differences in coronary atherosclerosis evaluated on coronary computed tomography angiography (CCTA) among groups and to facilitate clinical management.<br /><b>Methods</b><br />Clinical data from 1157 T2DM patients with coronary atherosclerosis who underwent CCTA in our hospital from January 2018 to September 2021 were retrospectively collected. The coronary artery segment plaque type and stenosis, the number of involved vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) were evaluated and calculated. Unsupervised clustering analysis based on clinical information was used (cluster 1: n = 463; cluster 2: n = 341; cluster 3: n = 353). The association of coronary plaque characteristics with cluster groups was evaluated.<br /><b>Results</b><br />The clinical data among the three groups were different in several aspects: (1) Cluster 1 had the least male patients (41.7%), the lowest proportion of patients with smoking (0%) or alcohol history (0.9%), and the lowest level of serum creatinine (74.46 ± 22.18 µmol/L); (2) Cluster 2 had the shortest duration of diabetes (7.90 ± 8.20 years) and was less likely to be treated with diabetes (42.2%) or statins (17.6%) and (3) Cluster 3 was the youngest (65.89 ± 10.15 years old) and had the highest proportion of male patients (96.6%), the highest proportion of patients with smoking (91.2%) and alcohol (59.8%) history, the highest level of eGFR (83.81 ± 19.06 ml/min/1.73m<sup>2</sup>), and the lowest level of HDL-C (1.07 ± 0.28 mmol/L). The CCTA characteristics varied with different clusters: (1) Cluster 1 had the largest number of segments with calcified plaques (2.43 ± 2.46) and the least number of segments with mixed plaques (2.24 ± 2.59) and obstructive stenosis (0.98 ± 2.00); (2) Cluster 1 had the lowest proportion of patients with mixed plaques (68%) and obstructive stenosis (32.2%); (3) Cluster 3 had more segments with noncalcified plaques than cluster 1 (0.63 ± 1.02 vs 0.40 ± 0.78, P < 0.05) and the highest proportion of patients with noncalcified plaques (39.9%) and (4) There was no significant difference in the extent of coronary plaques among the three clusters.<br /><b>Conclusions</b><br />The unsupervised clustering method could address T2DM patients with heterogeneous clinical indicators and identify groups with different types of coronary plaque and degrees of coronary stenosis. This method has the potential for patient stratification, which is essential for the clinical management of T2DM patients with coronary atherosclerosis.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 28 Nov 2022; 21:259</small></div>
Jiang Y, Yang ZG, Wang J, Shi R, ... Yan WF, Li Y
Cardiovasc Diabetol: 28 Nov 2022; 21:259 | PMID: 36443722
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<div><h4>Association between triglyceride glucose index and worsening heart failure in significant secondary mitral regurgitation following percutaneous coronary intervention.</h4><i>Huang H, Li Q, Liu J, Qiao L, ... Liu J, Liu Y</i><br /><b>Background</b><br />The triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade  ≥ 2) following percutaneous coronary intervention (PCI).<br /><b>Methods</b><br />This study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery.<br /><b>Results</b><br />A total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59-3.72; P < 0.001). The addition of TyG to risk factors such as N-terminal pro brain natriuretic peptide and clinical models improved the predictive ability of TyG for worsening HF.<br /><b>Conclusions</b><br />Elevated preprocedural TyG index is a significant and independent risk factor for worsening HF in sMR following PCI that can be used for risk stratification.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 28 Nov 2022; 21:260</small></div>
Huang H, Li Q, Liu J, Qiao L, ... Liu J, Liu Y
Cardiovasc Diabetol: 28 Nov 2022; 21:260 | PMID: 36443743
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<div><h4>Endotrophin is a risk marker of complications in CANagliflozin cardioVascular Assessment Study (CANVAS): a randomized controlled trial.</h4><i>Rasmussen DGK, Hansen MK, Blair J, Jatkoe TA, ... Karsdal MA, Genovese F</i><br /><b>Background</b><br />Enhanced de-novo collagen type VI (COL VI) formation has been associated with kidney and cardiovascular fibrosis. We hypothesized that endotrophin (ETP), a product specifically generated during collagen type VI formation, may be prognostic for heart failure (HF), cardiovascular death (CVD), kidney endpoints, and all-cause mortality in patients with type 2 diabetes.<br /><b>Methods</b><br />We measured ETP in plasma (P-ETP) and urine (U-ETP) samples collected at baseline and follow-up (year 3) from the randomized controlled trial, CANagliflozin cardioVascular Assessment Study (CANVAS), by use of the PRO-C6 ELISA measuring COL VI formation and ETP. At baseline, plasma and urine samples were available for 3531 and 3423 patients, respectively. At year 3, plasma and urine samples were available for 2178 (61.7%) and 2070 (60.5%) patients, respectively Patients were followed for a median of 6.1 years, and endpoints included: incident HF, CVD, three kidney composite endpoints, and all-cause mortality. Backward selection was used to identify variables to be included in the analyses. Robustness of the association with outcome was assessed by bootstrap analyses.<br /><b>Results</b><br />In univariable analysis, P-ETP predicted all investigated outcomes (all p < 0.0001), remained independently associated with all outcomes after adjustment for conventional risk factors (all p < 0.004), and increased C-statistics of the models for the outcomes HF, CVD, HFCVD, all-cause mortality, and kidney composite 2 (ΔC ≥ 0.002). In bootstrap analysis, P-ETP was retained with a frequency ranging from 41.0 to 98.4% for all outcomes. Levels of U-ETP were associated with outcomes in univariable analysis, but associations with most outcomes were lost after adjustment for conventional risk factors. The increase in P-ETP over time was greater with increasing albuminuria stage (p < 0.0001) and was independently associated with the kidney endpoints (p < 0.03). In the placebo arm, the increase in P-ETP was prognostic for all-cause mortality (HR [95% CI]; 1.14 [1.05-1.23], p = 0.003). Whereas levels of P-ETP were not impacted by treatment, levels of U-ETP significantly increased with canagliflozin treatment.<br /><b>Conclusions</b><br />P-ETP generated during COL VI formation predicts cardiovascular, kidney and mortality outcomes in patients with type 2 diabetes. As ETP identifies patients at increased risk of experiencing relevant outcomes, it may be used for patient enrichment in future clinical trials. Trial Registry Number (ClinicalTrials.gov Identifier): NCT01032629.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 28 Nov 2022; 21:261</small></div>
Rasmussen DGK, Hansen MK, Blair J, Jatkoe TA, ... Karsdal MA, Genovese F
Cardiovasc Diabetol: 28 Nov 2022; 21:261 | PMID: 36443792
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<div><h4>Combined evaluation of arterial stiffness, glycemic control and hypertension for macrovascular complications in type 2 diabetes.</h4><i>Wu Z, Yu S, Zhang H, Guo Z, ... Tao L, Guo X</i><br /><b>Background</b><br />Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication.<br /><b>Methods</b><br />A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0-4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).<br /><b>Results</b><br />The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42-5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61-4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication.<br /><b>Conclusion</b><br />This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 28 Nov 2022; 21:262</small></div>
Wu Z, Yu S, Zhang H, Guo Z, ... Tao L, Guo X
Cardiovasc Diabetol: 28 Nov 2022; 21:262 | PMID: 36443820
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<div><h4>Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022).</h4><i>Banach M, Surma S, Reiner Z, Katsiki N, ... Rizzo M, Kastelein J</i><br /><AbstractText>Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians\' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients\' group.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 28 Nov 2022; 21:263</small></div>
Banach M, Surma S, Reiner Z, Katsiki N, ... Rizzo M, Kastelein J
Cardiovasc Diabetol: 28 Nov 2022; 21:263 | PMID: 36443827
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<div><h4>Admission glucose as a prognostic marker for all-cause mortality and cardiovascular disease.</h4><i>Djupsjö C, Kuhl J, Andersson T, Lundbäck M, Holzmann MJ, Nyström T</i><br /><b>Background</b><br />Diabetes and prediabetes are known risk factors for cardiovascular disease and associated with increased mortality risk. Whether patients with a random elevated blood glucose level but no history of diabetes are at a higher mortality and cardiovascular risk is not entirely known.<br /><b>Methods</b><br />A retrospective cohort study where patients (18-80 years) with no history of diabetes between 2006 and 2016 attending the emergency department (ED) in Sweden were included. Based on the first (index) blood glucose level patients were categorized into four groups: hypoglycemia (< 3.9 mmol/L), normal glucose tolerance (NGT) (3.9-7.8 mmol/L), dysglycemia (7.8-11.1 mmol/L), and hyperglycemia (> 11.1 mmol/L). Data was collected from four nationwide registers (National Patient Register, National Cause of Death Register, Prescribed Drug Register and Statistics Sweden). Cox regression was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality and cardiovascular outcomes using NGT as reference.<br /><b>Results</b><br />618,694 patients were included during a mean follow-up time of 3.9 years. According to the index blood glucose level: 1871 (0.3%) had hypoglycemia, 525,636 (85%) had NGT, 77,442 (13%) had dysglycemia, and 13,745 (2%) patients had hyperglycemia, respectively. During follow-up 44,532 (7.2%) deaths occurred. After multiple adjustments, mortality risk was highest in patients with hypoglycemia HR 2.58 (2.26-2.96) followed by patients with hyperglycemia HR 1.69 (1.63-1.76) and dysglycemia HR 1.16 (1.13-1.19). Risk for cardiovascular events: i.e., myocardial infarction, stroke and heart failure, were highest among patients with hyperglycemia HR 2.28 (2.13-2.44), HR 1.62 (1.51-1.74) and HR 1.60 (1.46-1.75), respectively.<br /><b>Conclusion</b><br />Patients with disturbed blood glucose level at ED admission have a higher mortality risk than patients with NGT. Patients with hyperglycemia have almost a two folded increased long-term mortality risk and more than a doubled risk for cardiovascular events compared to patients with NGT.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 26 Nov 2022; 21:258</small></div>
Djupsjö C, Kuhl J, Andersson T, Lundbäck M, Holzmann MJ, Nyström T
Cardiovasc Diabetol: 26 Nov 2022; 21:258 | PMID: 36435766
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<div><h4>The novel inflammatory biomarker GlycA and triglyceride-rich lipoproteins are associated with the presence of subclinical myocardial dysfunction in subjects with type 1 diabetes mellitus.</h4><i>Puig-Jové C, Julve J, Castelblanco E, Julián MT, ... Jensen MT, Alonso N</i><br /><b>Background</b><br />Subjects with Type 1 diabetes mellitus (T1DM) have an increased incidence of heart failure (HF). Several pathophysiological mechanisms have been involved in its development. The aim of this study was to analyze the potential contribution of the advanced lipoprotein profile and plasma glycosylation (GlycA) to the presence of subclinical myocardial dysfunction in subjects with T1DM.<br /><b>Methods</b><br />We included subjects from a Danish cohort of T1DM subjects (Thousand & 1 study) with either diastolic and/or systolic subclinical myocardial dysfunction, and a control group without myocardial dysfunction, matched by age, sex and HbA1c. All underwent a transthoracic echocardiogram and an advanced lipoprotein profile obtained by using the NMR-based Liposcale® test. GlycA NMR signal was also analyzed. Systolic dysfunction was defined as left ventricular ejection fraction ≤ 45% and diastolic dysfunction was considered as E/e\'≥12 or E/e\' 8-12 + volume of the left atrium > 34 ml/m2. To identify a metabolic profile associated with the presence of subclinical myocardial dysfunction, a multivariate supervised model of classification based on least squares regression (PLS-DA regression) was performed.<br /><b>Results</b><br />One-hundred forty-six subjects had diastolic dysfunction and 18 systolic dysfunction. Compared to the control group, patients with myocardial dysfunction had longer duration of diabetes (p = 0.005), and higher BMI (p = 0.013), serum NTproBNP concentration (p = 0.001), systolic blood pressure (p < 0.001), albuminuria (p < 0.001), and incidence of advanced retinopathy (p < 0.001). The supervised classification model identified a specific pattern associated with myocardial dysfunction, with a capacity to discriminate patients with myocardial dysfunction from controls. PLS-DA showed that triglyceride-rich lipoproteins (TGRLs), such as VLDL (total VLDL particles, large VLDL subclass and VLDL-TG content) and IDL (IDL cholesterol content), as well as the plasma concentration of GlycA, were associated with the presence of subclinical myocardial dysfunction.<br /><b>Conclusion</b><br />Proatherogenic TGRLs and the proinflammatory biomarker Glyc A are strongly associated to myocardial dysfunction in T1DM. These findings suggest a pivotal role of TGRLs and systemic inflammation in the development of subclinical myocardial dysfunction in T1DM.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 Nov 2022; 21:257</small></div>
Puig-Jové C, Julve J, Castelblanco E, Julián MT, ... Jensen MT, Alonso N
Cardiovasc Diabetol: 24 Nov 2022; 21:257 | PMID: 36434633
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<div><h4>Association of triglyceride-glucose index and traditional risk factors with cardiovascular disease among non-diabetic population: a 10-year prospective cohort study.</h4><i>Liu L, Wu Z, Zhuang Y, Zhang Y, ... Peng J, Yang J</i><br /><b>Background</b><br />The triglyceride-glucose (TyG) index is known as a reliable alternative marker of insulin resistance (IR), which has been regarded as a predictor of cardiovascular disease (CVD). However, whether TyG index can predict the risk and occurrence of CVD in non-diabetic population remains uncertain. The aim of this study was to explore the association between the TyG index and cardiovascular risk factors and to clarify the prognostic value of the TyG index for CVD, coronary heart disease (CHD) and stroke in non-diabetic general population in Eastern China.<br /><b>Methods</b><br />A total of 6095 cases without diagnosed diabetes and CVD were included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2) and the participants were divided into 4 groups according to the TyG index quartiles (Q1, Q2, Q3, Q4). The primary outcome was CVD, including CHD and stroke. Cox proportional hazards regression analysis was used to investigate the association between the TyG index and the risk of CVD.<br /><b>Results</b><br />During the 10-year follow-up, 357 (5.9%) participants of CVD, 224 (3.7%) participants of CHD and 151 (2.5%) participants of stroke were observed. The incidence of CVD increased with the TyG index quartiles. Multivariate Cox regression analysis showed that the hazard ratios [95% confidence interval (CI)] in Q4 group were respectively 1.484 (1.074-2.051) for CVD, 1.687 (1.105-2.575) for CHD and 1.402 (0.853-2.305) for stroke compared to Q1 group. Moreover, adding the TyG index to models with traditional risk factors yielded a significant improvement in discrimination and reclassification of incident CVD and CHD.<br /><b>Conclusions</b><br />The TyG index is associated with cardiovascular risk factors and can be used as a useful, low-cost predictive marker for CVD and CHD risk in non-diabetic population.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 24 Nov 2022; 21:256</small></div>
Liu L, Wu Z, Zhuang Y, Zhang Y, ... Peng J, Yang J
Cardiovasc Diabetol: 24 Nov 2022; 21:256 | PMID: 36434636
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<div><h4>Time trends of cardiovascular risk management in type 1 diabetes - nationwide analyses of real-life data.</h4><i>Amadid H, Clemmensen KKB, Vistisen D, Persson F, Jørgensen ME</i><br /><b>Background</b><br />Individuals diagnosed with and treated for type 1 diabetes (T1D) have increased risk of micro- and macrovascular disease and excess mortality. Improving cardiovascular (CV) risk factors in individuals with T1D is known to reduce diabetes- related CV complications.<br /><b>Aim</b><br />To examine time trends in CV risk factor levels and CV-protective treatment patterns. Additionally, examine incidence rates of diabetes-related CV complications in relation to exposure CV-protective treatment.<br /><b>Methods</b><br />We analysed records from 41,630 individuals with T1D, registered anytime between 1996 and 2017 in a nationwide diabetes register. We obtained CV risk factor measurements (2010-2017), CV-protective drug profiles (1996-2017) and CV complication history (1977-2017) from additional nationwide health registers.<br /><b>Results</b><br />From 2010 to 2017 there were decreasing levels of HbA<sub>1c</sub>, LDL-C, and blood pressure. Decreasing proportion of smokers, individuals with glycaemic dysregulation (HbA<sub>1c</sub> ≥ 58 mmol/mol), dyslipidaemia (LDL-C > 2.6 mmol/l), and hypertension (≥ 140/85 mmHg). Yet, one fifth of the T1D population by January 1st, 2017 was severely dysregulated (HbA<sub>1c</sub> > 75 mmol/mol). A slight increase in levels of BMI and urinary albumin creatinine ratio and a slight decrease in estimated glomerular filtration rate (eGFR) levels was observed. By January 1st, 2017, one fourth of the T1D population had an eGFR < 60 ml/min/1.73 m<sup>2</sup>. The proportion of the T1D population redeeming lipid-lowering drugs (LLDs) increased from 5% in 2000 to 30% in 2010 followed by a plateau and then a decline. The proportion of the T1D population redeeming antihypertensive drugs (AHDs) increased from 28% in 1996 to 42% in 2010 followed by a tendency to decline. Use of LLDs was associated with lower incidence of micro- and macrovascular complications, while use of AHDs had higher incidence of CVD and CKD, when compared to non-use and discontinued use, respectively.<br /><b>Conclusion</b><br />Improvements were seen in CV risk factor control among individuals with T1D in Denmark between 2010 and 2017. However, there is clearly a gap between current clinical guidelines and clinical practice for CV risk management in T1D. Action is needed to push further improvements in CV risk control to reduce CVD and the related excess mortality.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Nov 2022; 21:255</small></div>
Amadid H, Clemmensen KKB, Vistisen D, Persson F, Jørgensen ME
Cardiovasc Diabetol: 23 Nov 2022; 21:255 | PMID: 36419118
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<div><h4>TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes.</h4><i>Zhu P, Lao G, Chen C, Luo L, Gu J, Ran J</i><br /><b>Background</b><br />Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes.<br /><b>Methods</b><br />This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39-1.30 mIU/L; medium-normal, 1.30-2.09 mIU/L; high-normal, 2.09-4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality.<br /><b>Results</b><br />During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07-1.61) and CVD (1.52; 1.08-2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12-1.73) and CVD (1.69; 1.17-2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants.<br /><b>Conclusion</b><br />Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 23 Nov 2022; 21:254</small></div>
Zhu P, Lao G, Chen C, Luo L, Gu J, Ran J
Cardiovasc Diabetol: 23 Nov 2022; 21:254 | PMID: 36419168
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<div><h4>The interplay of galectins-1, -3, and -9 in the immune-inflammatory response underlying cardiovascular and metabolic disease.</h4><i>Mansour AA, Krautter F, Zhi Z, Iqbal AJ, Recio C</i><br /><AbstractText>Galectins are β-galactoside-binding proteins that bind and crosslink molecules via their sugar moieties, forming signaling and adhesion networks involved in cellular communication, differentiation, migration, and survival. Galectins are expressed ubiquitously across immune cells, and their function varies with their tissue-specific and subcellular location. Particularly galectin-1, -3, and -9 are highly expressed by inflammatory cells and are involved in the modulation of several innate and adaptive immune responses. Modulation in the expression of these proteins accompany major processes in cardiovascular diseases and metabolic disorders, such as atherosclerosis, thrombosis, obesity, and diabetes, making them attractive therapeutic targets. In this review we consider the broad cellular activities ascribed to galectin-1, -3, and -9, highlighting those linked to the progression of different inflammatory driven pathologies in the context of cardiovascular and metabolic disease, to better understand their mechanism of action and provide new insights into the design of novel therapeutic strategies.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 19 Nov 2022; 21:253</small></div>
Mansour AA, Krautter F, Zhi Z, Iqbal AJ, Recio C
Cardiovasc Diabetol: 19 Nov 2022; 21:253 | PMID: 36403025
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<div><h4>Effects of second-line antihyperglycemic drugs on the risk of chronic kidney disease: applying a target trial approach to a hospital-based cohort of Thai patients with type 2 diabetes.</h4><i>Siriyotha S, Lukkunaprasit T, Looareesuwan P, Nimitphong H, ... Attia J, Thakkinstian A</i><br /><b>Background</b><br />The reno-protective effect of second-line treatments in type 2 diabetes has been assessed by clinical trials but generalizability to routine clinical practice is still uncertain. We aimed to assess the effectiveness of these treatments, when added to metformin, on the risk of chronic kidney disease (CKD).<br /><b>Methods</b><br />A real-world, hospital-based, type 2 diabetes cohort was retrospectively assembled at Ramathibodi Hospital from 2010 to 2019. Patients who received sulfonylureas (SU), thiazolidinediones (TZD), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose cotransporter-2 inhibitors (SGLT2i), as second-line antihyperglycemic treatment were included. Treatment effect models with inverse probability weighting and regression adjustment were used to estimate CKD risk according to treatment.<br /><b>Results</b><br />CKD was identified in 4,132 of the 24,777 patients with type 2 diabetes (16.7%). The CKD incidence (95% CI) was 4.1% (2.2%, 6.9%), 13.5% (12.5%, 14.6%), 14.8% (13.5%, 16.1%), and 18.0% (17.4%, 18.5%) for patients receiving SGLT2i, DPP4i, TZD, and SU treatment, respectively. The average treatment effects (i.e., the difference in CKD risk) for SGLT2i, DPP4i, and TZD compared to SU were - 0.142 (- 0.167, - 0.116), - 0.046 (- 0.059, - 0.034), and - 0.004 (- 0.023, 0.014), respectively, indicating a significant reduction in CKD risk of 14.2% and 4.6% in the SGLT2i and DPP4i groups, respectively, compared to the SU group. Furthermore, SGLT2i significantly reduced CKD risk by 13.7% (10.6%, 16.8%) and 9.5% (6.8%, 12.2%) when compared to TZD and DPP4i, respectively.<br /><b>Conclusions</b><br />Our study identified 14.2%, 13.7%, and 9.5% reduced CKD risk in Thai patients with type 2 diabetes who were treated with SGLT2i compared to those treated with SU, TZD, and DPP4i, respectively, in real-world clinical data. Previous evidence of a reno-protective effect of SGLT2i reported in other populations is consistent with our observations in this Southeast Asian cohort.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:248</small></div>
Siriyotha S, Lukkunaprasit T, Looareesuwan P, Nimitphong H, ... Attia J, Thakkinstian A
Cardiovasc Diabetol: 17 Nov 2022; 21:248 | PMID: 36397062
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<div><h4>Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study.</h4><i>Bae NY, Lee SR, Choi EK, Ahn HJ, ... Oh S, Lip GYH</i><br /><b>Background</b><br />It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF.<br /><b>Methods</b><br />Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed.<br /><b>Results</b><br />Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17-1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12-1.17], 1.15 [1.13-1.18], and 1.19 [1.67-1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not.<br /><b>Conclusions</b><br />Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:251</small></div>
Bae NY, Lee SR, Choi EK, Ahn HJ, ... Oh S, Lip GYH
Cardiovasc Diabetol: 17 Nov 2022; 21:251 | PMID: 36397079
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<div><h4>Association of triglyceride-glucose index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion: a multicenter hospital-based prospective cohort study.</h4><i>Wu L, Zhu J, Li C, Zhu J, Dai Z, Jiang Y</i><br /><b>Background</b><br />Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker of insulin resistance. Elevated TyG index was related to stroke recurrence. This study aimed to explore the associations between TyG index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion.<br /><b>Methods</b><br />From November 1, 2016 to February 28, 2021, consecutive acute ischemic stroke patients admitted within 1 week after onset were screened. The stroke mechanism was determined based on medical history, laboratory examinations, cardiac examinations, vascular examinations and neuroimaging. Nondiabetic patients with small vessel occlusion were enrolled and followed up for 1 year. The primary outcome was ischemic stroke recurrence. Logistic regression and Kaplan-Meier survival curve were used to analyze the association of the TyG index and stroke recurrence.<br /><b>Results</b><br />A total of 6100 acute ischemic stroke patients were screened, with 1970 nondiabetic patients with small vessel occlusion included and divided into 4 groups according to the TyG index quartiles (Q1: < 8.20; Q2: 8.20-8.53; Q3: 8.54-8.92; Q4: > 8.92). There were significant differences in age, body mass index, systolic blood pression, diastolic blood pressure, lipid-lowering agents, infarct location, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and stroke recurrence among the 4 groups. In the multi-adjusted models, compared to Q1 of the TyG index, the odds ratio for Q4 of the TyG index for stroke recurrence was 3.100 (1.366-8.019). The Kaplan-Meier survival (ischemic stroke-free) curves by quartiles of the TyG index also showed statistically significant differences (log-rank test, P = 0.004).<br /><b>Conclusions</b><br />Our findings suggested that the TyG index was associated with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion, and it could be a valuable biomarker for assessing the risk of ischemic stroke recurrence in these patients.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:250</small></div>
Abstract
<div><h4>Body-weight variability and risk of cardiovascular outcomes in patients with type 1 diabetes: a retrospective observational analysis of data from the DCCT/EDIC population.</h4><i>Petria I, Albuquerque S, Varoquaux G, Vie JJ, ... Velho G, Potier L</i><br /><b>Background</b><br />Cardiovascular risk and body-weight management are both emerging challenges of type 1 diabetes care. We evaluated the association between intraindividual variability of body-weight and risk of cardiovascular events in people with type 1 diabetes.<br /><b>Methods</b><br />We analyzed 1,398 participants from the DCCT/EDIC studies. Five indices of intraindividual variability of body-weight were calculated for each participant taking into account body-weight measures obtained during the DCCT follow-up (average 6 ± 2 years). The Average Successive Variability (ASV) index, the main variable of interest, was defined as the average absolute difference between successive body-weight measures. The primary outcome was a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction or stroke, or cardiovascular death) occurring during the subsequent EDIC follow-up (20 ± 3 years). All-cause death was a secondary outcome. Risk of outcomes were assessed by Cox proportional hazards regression analyses, adjusted for traditional cardiovascular risks factors, including BMI.<br /><b>Results</b><br />The cumulative incidence of MACE and all-cause death during follow-up were 5.6% (n = 79) and 6.8% (n = 95), respectively. The adjusted Hazard Ratio (HR) for MACE by every increase of 1 standard deviation (SD) of ASV was 1.34 (95% CI, 1.06-1.66), p = 0.01. For all-cause death, the adjusted HR for 1 SD increase of ASV was 1.25 (1.03-1.50), p = 0.03. Similar results were observed when considering the other indices of intraindividual variability of body-weight.<br /><b>Conclusions</b><br />High body-weight variability (body-weight cycling) is associated with increased risk of MACE and all-cause death in people with type 1 diabetes, independently of the BMI and traditional cardiovascular risk factors.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:247</small></div>
Petria I, Albuquerque S, Varoquaux G, Vie JJ, ... Velho G, Potier L
Cardiovasc Diabetol: 17 Nov 2022; 21:247 | PMID: 36397092
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<div><h4>Clinical significance of neutrophil gelatinase-associated lipocalin and sdLDL-C for coronary artery disease in patients with type 2 diabetes mellitus aged ≥ 65 years.</h4><i>Chen Y, Fu Y, Wang S, Chen P, ... Gu F, Li X</i><br /><b>Background:</b><br/>and aims</b><br />Although type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share many common pathological and physiological characteristics, there are few studies assessing the predictive capacity of novel biomarkers in occurrence and development of CAD in T2DM patients aged ≥ 65 years. In addition, T2DM patients aged ≥ 65 years are prone to CAD. Therefore, it is of great significance to find novel biomarkers for the development CAD in T2DM.<br /><b>Methods</b><br />In this retrospective cohort study, 579 T2DM patients aged ≥ 65 years were consecutively enrolled in this work, and 177 of whom had major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular or cerebrovascular death, acute coronary syndrome, coronary stent implantation, and stroke) during the follow up. Univariate and multivariate factors were employed to analyze the correlation between each variable and the occurrence of MACCE, and the Spearman\'s rank correlation analysis was performed to assess the relationships between Neutrophil gelatinase-associated lipocalin (NGAL) and small dense low-density lipoprotein-cholesterol (LDL-C) (sdLDL-C). The receiver operating characteristic (ROC) curve was adopted to determine the predictive value of NGAL and sdLDL-C elevation for MACCE in T2DM patients aged ≥ 65 years.<br /><b>Results</b><br />After a median 48 months follow-up [19, (10 ~ 32) ], the levels of NGAL, sdLDL-C, hemoglobin A1c (HbA1c), LDL-C, and apolipoprotein B (ApoB) were significantly higher while those of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A I (ApoA-I) were lower in MACCE positive group. NGAL correlated to body mass index (BMI) (r = 0.391, P = 0.001) and triglyceride (TG) (r = 0.228, P = 0.032), and high-sensitivity CRP (hsCRP) (r = 0.251, P = 0.007), and neutrophils (r = 0.454, P = 0.001), sdlDL-C level was found to be positively correlated with LDL-C (r = 0.413, P = 0.001), TG (r = 0.432, P = 0.001), and ApoB (r = 0.232, P = 0.002); and it was negatively correlated with HDL-C (r = -0.362, P = 0.031) and ApoA-I (r = -0.402, P = 0.001). Age-adjusted Cox regression analysis showed that NGAL (HR = 1.006, 95% confidence interval (CI): 1.005-1.008, P < 0.001) and sdLDL-C (HR = 1.052, 95% CI: 1.037-1.066, P < 0.001) were independently associated with occurrence of MACCE. ROC curve analysis showed that NGAL (area under ROC (AUC) = 0.79, 95% CI: 0.75-0.84, P < 0.001) and sdlDL-C (AUC = 0.76, 95% CI: 0.72-0.80, P < 0.001) could predict the occurrence of MACCE (area under ROC. NGAL combined with sdlDL-C could predict the occurrence of MACCE well (AUC = 0.87, 95% CI: 0.84-0.90, P < 0.001).<br /><b>Conclusion</b><br />The higher NGAL and sdLDL-C in T2DM patients aged ≥ 65 years were significantly and independently associated with the risk of MACCE, and showed higher clinical values than other lipid biomarkers or other chronic inflammation, so they were expected to be the most effective predictors of MACCE assessment.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:252</small></div>
Abstract
<div><h4>Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study.</h4><i>Chyrchel B, Kruszelnicka O, Surdacki A</i><br /><b>Background</b><br />Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y<sub>12</sub> antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y<sub>12</sub> blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status.<br /><b>Methods</b><br />Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension.<br /><b>Results</b><br />Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y<sub>12</sub> antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM.<br /><b>Conclusions</b><br />Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 17 Nov 2022; 21:249</small></div>
Abstract
<div><h4>Diabetes mellitus in transfemoral transcatheter aortic valve implantation: a propensity matched analysis.</h4><i>van Nieuwkerk AC, Santos RB, Mata RB, Tchétché D, ... Mehran R, Delewi R</i><br /><b>Background</b><br />Diabetes Mellitus (DM) affects a third of patients with symptomatic severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). DM is a well-known risk factor for cardiac surgery, but its prognostic impact in TAVI patients remains controversial. This study aimed to evaluate outcomes in diabetic patients undergoing TAVI.<br /><b>Methods</b><br />This multicentre registry includes data of > 12,000 patients undergoing transfemoral TAVI. We assessed baseline patient characteristics and clinical outcomes in patients with DM and without DM. Clinical outcomes were defined by the second valve academic research consortium. Propensity score matching was applied to minimize potential confounding.<br /><b>Results</b><br />Of the 11,440 patients included, 31% (n = 3550) had DM and 69% (n = 7890) did not have DM. Diabetic patients were younger but had an overall worse cardiovascular risk profile than non-diabetic patients. All-cause mortality rates were comparable at 30 days (4.5% vs. 4.9%, RR 0.9, 95%CI 0.8-1.1, p = 0.43) and at one year (17.5% vs. 17.4%, RR 1.0, 95%CI 0.9-1.1, p = 0.86) in the unmatched population. Propensity score matching obtained 3281 patient-pairs. Also in the matched population, mortality rates were comparable at 30 days (4.7% vs. 4.3%, RR 1.1, 95%CI 0.9-1.4, p = 0.38) and one year (17.3% vs. 16.2%, RR 1.1, 95%CI 0.9-1.2, p = 0.37). Other clinical outcomes including stroke, major bleeding, myocardial infarction and permanent pacemaker implantation, were comparable between patients with DM and without DM. Insulin treated diabetics (n = 314) showed a trend to higher mortality compared with non-insulin treated diabetics (n = 701, Hazard Ratio 1.5, 95%CI 0.9-2.3, p = 0.08). EuroSCORE II was the most accurate risk score and underestimated 30-day mortality with an observed-expected ratio of 1.15 in DM patients, STS-PROM overestimated actual mortality with a ratio of 0.77 and Logistic EuroSCORE with 0.35.<br /><b>Conclusion</b><br />DM was not associated with mortality during the first year after TAVI. DM patients undergoing TAVI had low rates of mortality and other adverse clinical outcomes, comparable to non-DM TAVI patients. Our results underscore the safety of TAVI treatment in DM patients.<br /><b>Trial registration</b><br />The study is registered at clinicaltrials.gov (NCT03588247).<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 16 Nov 2022; 21:246</small></div>
van Nieuwkerk AC, Santos RB, Mata RB, Tchétché D, ... Mehran R, Delewi R
Cardiovasc Diabetol: 16 Nov 2022; 21:246 | PMID: 36384656
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<div><h4>Comparison of the effects of triglyceride variability and exposure estimate on clinical prognosis in diabetic patients.</h4><i>Koh SM, Chung SH, Yum YJ, Park SJ, ... Kim YH, Kim EJ</i><br /><b>Background</b><br />Hypertriglyceridemia is an important feature of dyslipidemia in type 1 and type 2 diabetic patients and associated with the development of atherosclerotic cardiovascular disease. Recently, variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the clinical impact of serum triglyceride variability, and their cumulative exposure estimates on cardiovascular prognosis in diabetic patients.<br /><b>Methods</b><br />A total of 25,933 diabetic patients who had serum triglyceride levels measured at least 3 times and did not have underlying malignancy, myocardial infarction (MI), and stroke during the initial 3 years (modeling phase) were selected from three tertiary hospitals. They were divided into a high/low group depending on their coefficient of variation (CV) and cumulative exposure estimate (CEE). Incidence of major adverse event (MAE), a composite of all-cause death, MI, and stroke during the following 5 years were compared between groups by multivariable analysis after propensity score matching.<br /><b>Results</b><br />Although there was a slight difference, both the high CV group and the high CEE group had a higher cardiovascular risk profile including male-dominance, smoking, alcohol, dyslipidemia, and chronic kidney disease compared to the low groups. After the propensity score matching, the high CV group showed higher MAE incidence compared to the low CV group (9.1% vs 7.7%, p = 0.01). In contrast, there was no significant difference of MAE incidence between the high CEE group and the low CEE group (8.6% vs 9.1%, p = 0.44). After the multivariable analysis with further adjustment for potential residual confounding factors, the high CV was suggested as an independent risk predictor for MAE (HR 1.19 [95% CI 1.03-1.37]).<br /><b>Conclusion</b><br />Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MAE in diabetic patients.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 15 Nov 2022; 21:245</small></div>
Koh SM, Chung SH, Yum YJ, Park SJ, ... Kim YH, Kim EJ
Cardiovasc Diabetol: 15 Nov 2022; 21:245 | PMID: 36380325
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<div><h4>Impact of diabetes mellitus on long-term clinical and graft outcomes after off-pump coronary artery bypass grafting with pure bilateral skeletonized internal thoracic artery grafts.</h4><i>Park I, Choi KB, Ahn JH, Kim WS, Lee YT, Jeong DS</i><br /><b>Background</b><br />The effect of diabetes mellitus (DM) on the long-term outcomes of coronary artery bypass graft (CABG) remained debatable and various strategies exist for CABG; hence, clarifying the effects of DM on CABG outcomes is difficult. The current study aimed to evaluate the effect of DM on clinical and graft-related outcomes after CABG with bilateral internal thoracic artery (BITA) grafts.<br /><b>Methods</b><br />From January 2001 to December 2017, 3395 patients who underwent off-pump CABG (OPCAB) with BITA grafts were enrolled. The study population was stratified according to preoperative DM. The primary endpoint was cardiac death and the secondary endpoints were myocardial infarction (MI), revascularization, graft failure, stroke, postoperative wound infection, and a composite endpoint of cardiac death, MI, and revascularization. Multiple sensitivity analyses, including Cox proportional hazard regression and propensity-score matching analyses, were performed to adjust baseline differences.<br /><b>Results</b><br />After CABG, the DM group showed similar rates of cardiac death, MI, or revascularization and lower rates of graft failure at 10 years (DM vs. non-DM, 19.0% vs. 24.3%, hazard ratio [HR] 0.711, 95% confidence interval [CI] 0.549-0.925; P = 0.009) compared to the non-DM group. These findings were consistent after multiple sensitivity analyses. In the subgroup analysis, the well-controlled DM group, which is defined as preoperative hemoglobin A1c (HbA1c) of < 7%, showed lower postoperative wound infection rates (well-controlled DM vs. poorly controlled DM, 3.7% vs. 7.3%, HR 0.411, 95% CI 0.225-0.751; P = 0.004) compared to the poorly controlled DM group, which was consistent after propensity-score matched analysis.<br /><b>Conclusions</b><br />OPCAB with BITA grafts showed excellent and comparable long-term clinical outcomes in patients with and without DM. DM might have a protective effect on competition and graft failure of ITA. Strict preoperative hyperglycemia control with target HbA1c of < 7% might reduce postoperative wound infection and facilitate the use of BITA in CABG.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 15 Nov 2022; 21:243</small></div>
Abstract
<div><h4>Association between the triglyceride-glucose index and carotid plaque incidence: a longitudinal study.</h4><i>Zhang Y, Wu Z, Li X, Wei J, Zhang Q, Wang J</i><br /><b>Background</b><br />Carotid plaque and triglyceride-glucose (TyG) index are associated with insulin resistance. However, a highly debated question is whether there is an association between the TyG index and carotid plaque incidence. Thus we performed an in-depth longitudinal study to investigate the relationship between carotid plaque occurrence and the TyG index among Chinese individuals.<br /><b>Methods</b><br />Two thousand and three hundred seventy subjects (1381 males and 989 females) were enrolled and followed up for three years. The subjects were stratified into four groups based on the quartile of the TyG index at baseline. Univariate and multivariate Cox proportional hazard models were conducted to examine the role of TyG played in the carotid plaque. The strength of association was expressed as hazard ratio (HR) and 95% confidence interval (CI).<br /><b>Results</b><br />After three years of follow-up, 444 subjects were detected with newly formed carotid plaque. The overall 3-year cumulative carotid plaque incidence was 18.7%, and the risk of carotid plaque increased with elevated TyG index (p < 0.001). The Cox regression analysis showed that males (HR: 1.33, 95% CI: 1.10-1.61), and people with higher systolic blood pressure (HR:1.01, 95% CI: 1.01-1.02), lower high-density lipoprotein cholesterol (HR: 0.68, 95% CI: 0.50-0.93), diabetes (HR: 2.21, 95% CI: 1.64-2.97), and hypertension (HR:1.49, 95% CI: 1.23-1.81) had a significantly increased risk for the carotid plaque formation. Similar results remained in the sensitivity analysis.<br /><b>Conclusions</b><br />The TyG index can be used as a dose-responsive indicator of carotid plaque in the Chinese population. Elderly males with dyslipidemia, diabetes, or hypertension should be more vigilant about their TyG index since they are susceptible to developing carotid plaque. Physicians are encouraged to monitor the TyG index to help identify and treat patients with carotid plaque at an early stage.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 15 Nov 2022; 21:244</small></div>
Zhang Y, Wu Z, Li X, Wei J, Zhang Q, Wang J
Cardiovasc Diabetol: 15 Nov 2022; 21:244 | PMID: 36380351
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<div><h4>Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms.</h4><i>Vergès B, Aboyans V, Angoulvant D, Boutouyrie P, ... Mohammedi K, Amarenco P</i><br /><AbstractText>Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood-brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.</AbstractText><br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 15 Nov 2022; 21:242</small></div>
Vergès B, Aboyans V, Angoulvant D, Boutouyrie P, ... Mohammedi K, Amarenco P
Cardiovasc Diabetol: 15 Nov 2022; 21:242 | PMID: 36380358
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<div><h4>Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.</h4><i>Won KB, Lee BK, Lin FY, Hadamitzky M, ... Min JK, Chang HJ</i><br /><b>Background</b><br />The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images.<br /><b>Methods</b><br />A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV).<br /><b>Results</b><br />During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017).<br /><b>Conclusion</b><br />In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study.<br /><b>Trial registration</b><br />ClinicalTrials.gov NCT02803411.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Nov 2022; 21:239</small></div>
Abstract
<div><h4>Risk factors for cardiovascular disease in patients with metabolic-associated fatty liver disease: a machine learning approach.</h4><i>Drożdż K, Nabrdalik K, Kwiendacz H, Hendel M, ... Gumprecht J, Lip GYH</i><br /><b>Background</b><br />Nonalcoholic fatty liver disease is associated with an increased cardiovascular disease (CVD) risk, although the exact mechanism(s) are less clear. Moreover, the relationship between newly redefined metabolic-associated fatty liver disease (MAFLD) and CVD risk has been poorly investigated. Data-driven machine learning (ML) techniques may be beneficial in discovering the most important risk factors for CVD in patients with MAFLD.<br /><b>Methods</b><br />In this observational study, the patients with MAFLD underwent subclinical atherosclerosis assessment and blood biochemical analysis. Patients were split into two groups based on the presence of CVD (defined as at least one of the following: coronary artery disease; myocardial infarction; coronary bypass grafting; stroke; carotid stenosis; lower extremities artery stenosis). The ML techniques were utilized to construct a model which could identify individuals with the highest risk of CVD. We exploited the multiple logistic regression classifier operating on the most discriminative patient\'s parameters selected by univariate feature ranking or extracted using principal component analysis (PCA). Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for the investigated classifiers, and the optimal cut-point values were extracted from the ROC curves using the Youden index, the closest to (0, 1) criteria and the Index of Union methods.<br /><b>Results</b><br />In 191 patients with MAFLD (mean age: 58, SD: 12 years; 46% female), there were 47 (25%) patients who had the history of CVD. The most important clinical variables included hypercholesterolemia, the plaque scores, and duration of diabetes. The five, ten and fifteen most discriminative parameters extracted using univariate feature ranking and utilized to fit the ML models resulted in AUC of 0.84 (95% confidence interval [CI]: 0.77-0.90, p < 0.0001), 0.86 (95% CI 0.80-0.91, p < 0.0001) and 0.87 (95% CI 0.82-0.92, p < 0.0001), whereas the classifier fitted over 10 principal components extracted using PCA followed by the parallel analysis obtained AUC of 0.86 (95% CI 0.81-0.91, p < 0.0001). The best model operating on 5 most discriminative features correctly identified 114/144 (79.17%) low-risk and 40/47 (85.11%) high-risk patients.<br /><b>Conclusion</b><br />A ML approach demonstrated high performance in identifying MAFLD patients with prevalent CVD based on the easy-to-obtain patient parameters.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Nov 2022; 21:240</small></div>
Drożdż K, Nabrdalik K, Kwiendacz H, Hendel M, ... Gumprecht J, Lip GYH
Cardiovasc Diabetol: 12 Nov 2022; 21:240 | PMID: 36371249
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<div><h4>The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states.</h4><i>Huang R, Dai Q, Chang L, Wang Z, ... Xu B, Wang L</i><br /><b>Background</b><br />Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous.<br /><b>Methods</b><br />A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan-Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states.<br /><b>Results</b><br />MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan-Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07-1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17-1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13-1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14-1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05).<br /><b>Conclusions</b><br />Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 12 Nov 2022; 21:241</small></div>
Huang R, Dai Q, Chang L, Wang Z, ... Xu B, Wang L
Cardiovasc Diabetol: 12 Nov 2022; 21:241 | PMID: 36371183
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<div><h4>Impact of T2DM on right ventricular systolic dysfunction and interventricular interactions in patients with essential hypertension: evaluation using CMR tissue tracking.</h4><i>Li XM, Yan WF, Jiang L, Shi K, ... Guo YK, Yang ZG</i><br /><b>Background</b><br />Previous studies reported that there was right ventricular (RV) systolic dysfunction in patients with hypertension. The aim of this study was to evaluate the impact of type 2 diabetes mellitus (T2DM) on RV systolic dysfunction and interventricular interactions using cardiac magnetic resonance feature tracking (CMR-FT) in patients with essential hypertension.<br /><b>Methods and methods</b><br />Eighty-five hypertensive patients without T2DM [HTN(T2DM -)], 58 patients with T2DM [HTN(T2DM +)] and 49 normal controls were included in this study. The biventricular global radial, circumferential and longitudinal peak strains (GRS, GCS, GLS, respectively) and RV regional strains at the basal-, mid- and apical-cavity, were calculated with CMR-FT and compared among controls and different patient groups. Backward stepwise multivariable linear regression analyses were used to determine the effects of T2DM and left ventricular (LV) strains on RV strains.<br /><b>Results</b><br />The biventricular GLS and RV apical longitudinal strain deteriorated significantly from controls, through HTN(T2DM-), to HTN(T2DM +) groups. RV middle longitudinal strain in patient groups were significantly reduced, and LV GRS and GCS and RV basal longitudinal strain were decreased in HTN(T2DM +) but preserved in HTN(T2DM-) group. Multivariable regression analyses adjusted for covariates demonstrated that T2DM was independently associated with LV strains (LV GRS: β = - 4.278, p = 0.004, model R<sup>2</sup> = 0.285; GCS: β = 1.498, p = 0.006, model R<sup>2</sup> = 0.363; GLS: β = 1.133, p = 0.007, model R<sup>2</sup> = 0.372) and RV GLS (β = 1.454, p = 0.003, model R<sup>2</sup> = 0.142) in hypertension. When T2DM and LV GLS were included in the multiple regression analysis, both T2DM and LV GLS (β = 0.977 and 0.362, p = 0.039 and < 0.001, model R<sup>2</sup> = 0.224) were independently associated with RV GLS.<br /><b>Conclusions</b><br />T2DM exacerbates RV systolic dysfunction in patients with hypertension, which may be associated with superimposed LV dysfunction by coexisting T2DM and suggests adverse interventricular interactions.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 09 Nov 2022; 21:238</small></div>
Li XM, Yan WF, Jiang L, Shi K, ... Guo YK, Yang ZG
Cardiovasc Diabetol: 09 Nov 2022; 21:238 | PMID: 36352469
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Abstract
<div><h4>Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials.</h4><i>Lin Y, Cai Z, Yuan J, Liu H, ... Geng Q, Dong S</i><br /><b>Background</b><br />Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF.<br /><b>Methods</b><br />Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis.<br /><b>Results</b><br />Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)].<br /><b>Conclusions</b><br />No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 08 Nov 2022; 21:237</small></div>
Abstract
<div><h4>NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.</h4><i>Ciardullo S, Rea F, Cannistraci R, Muraca E, ... Mortara A, Perseghin G</i><br /><b>Background</b><br />Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels.<br /><b>Methods</b><br />Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015.<br /><b>Results</b><br />After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex.<br /><b>Conclusions</b><br />Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 07 Nov 2022; 21:236</small></div>
Ciardullo S, Rea F, Cannistraci R, Muraca E, ... Mortara A, Perseghin G
Cardiovasc Diabetol: 07 Nov 2022; 21:236 | PMID: 36344968
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Abstract
<div><h4>The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial.</h4><i>Sasso FC, Simeon V, Galiero R, Caturano A, ... Minutolo R, NID-2 study group Investigators</i><br /><b>Background</b><br />Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes.<br /><b>Methods</b><br />Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0-1 risk factor (absent/low); 2-3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase.<br /><b>Results</b><br />Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04-3.52, P = 0.038 and 1.96, 95%CI 1.02-3.8, P = 0,045, respectively, vs absent/low risk group).<br /><b>Conclusions</b><br />This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.<br /><br />© 2022. The Author(s).<br /><br /><small>Cardiovasc Diabetol: 07 Nov 2022; 21:235</small></div>
Sasso FC, Simeon V, Galiero R, Caturano A, ... Minutolo R, NID-2 study group Investigators
Cardiovasc Diabetol: 07 Nov 2022; 21:235 | PMID: 36344978
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This program is still in alpha version.