Journal: Cardiovasc Diabetol

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Abstract

Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes.

Taya N, Katakami N, Mita T, Okada Y, ... Shimomura I, Watada H
Background
The association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages.
Methods
We conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics.
Results
Among 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, β = - 5.822; 95% CI - 8.875 to - 2.768, P < 0.001), glucose coefficient of variation (β = - 0.418; - 0.685 to - 0.151, P = 0.002), mean amplitude of glycemic excursion (β = - 1.689; - 2.567 to - 0.811, P < 0.001), mean of daily differences (β = - 6.500; - 9.758 to - 3.241, P < 0.001), and interquartile range (β = - 4.289; - 6.964 to - 1.614, P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT.
Conclusions
Continuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.



Cardiovasc Diabetol: 03 May 2021; 20:95
Taya N, Katakami N, Mita T, Okada Y, ... Shimomura I, Watada H
Cardiovasc Diabetol: 03 May 2021; 20:95 | PMID: 33947398
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Abstract

Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double-blind placebo-controlled clinical trials.

Yokote K, Yamashita S, Arai H, Araki E, ... Suganami H, Ishibashi S
Background
Increased risk of cardiovascular events is associated not only with dyslipidemias, but also with abnormalities in glucose metabolism and liver function. This study uses pooled analysis to explore the in-depth effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα) already known to decrease elevated triglycerides, on glucose metabolism and liver function in patients with hypertriglyceridemia.
Methods
We performed a post-hoc analysis of six phase 2 and phase 3 Japanese randomized double-blind placebo-controlled trials that examined the effects of daily pemafibrate 0.1 mg, 0.2 mg, and 0.4 mg on glucose metabolism markers and liver function tests (LFTs). Primary endpoints were changes in glucose metabolism markers and LFTs from baseline after 12 weeks of pemafibrate treatment. All adverse events and adverse drug reactions were recorded as safety endpoints.
Results
The study population was 1253 patients randomized to placebo (n = 298) or pemafibrate 0.1 mg/day (n = 127), 0.2 mg/day (n = 584), or 0.4 mg/day (n = 244). Participant mean age was 54.3 years, 65.4 % had BMI ≥ 25 kg/m2, 35.8 % had type 2 diabetes, and 42.6 % had fatty liver. Fasting glucose, fasting insulin, and HOMA-IR decreased significantly in all pemafibrate groups compared to placebo. The greatest decrease was for pemafibrate 0.4 mg/day: least square (LS) mean change from baseline in fasting glucose - 0.25 mmol/L; fasting insulin - 3.31 µU/mL; HOMA-IR - 1.28. ALT, γ-GT, ALP, and total bilirubin decreased significantly at all pemafibrate doses vs. placebo, with the greatest decrease in the pemafibrate 0.4 mg/day group: LS mean change from baseline in ALT - 7.6 U/L; γ-GT - 37.3 U/L; ALP - 84.7 U/L; and total bilirubin - 2.27 µmol/L. Changes in HbA1c and AST did not differ significantly from placebo in any pemafibrate groups in the overall study population. The decreases from baseline in LFTs and glucose metabolism markers except for HbA1c were notable among patients with higher baseline values. FGF21 increased significantly in all pemafibrate groups compared to placebo, with the greatest increase in the pemafibrate 0.4 mg/day group. Adverse event rates were similar in all groups including placebo.
Conclusions
In patients with hypertriglyceridemia, pemafibrate can improve glucose metabolism and liver function, and increase FGF21, without increasing adverse event risk.



Cardiovasc Diabetol: 03 May 2021; 20:96
Yokote K, Yamashita S, Arai H, Araki E, ... Suganami H, Ishibashi S
Cardiovasc Diabetol: 03 May 2021; 20:96 | PMID: 33947390
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Abstract

Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON.

Lorenzatti AJ, Monsalvo ML, López JAG, Wang H, Rosenson RS
Background
Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM.
Methods
This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD.
Results
In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12.
Conclusions
Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.



Cardiovasc Diabetol: 29 Apr 2021; 20:94
Lorenzatti AJ, Monsalvo ML, López JAG, Wang H, Rosenson RS
Cardiovasc Diabetol: 29 Apr 2021; 20:94 | PMID: 33941192
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Abstract

The impact of weight loss related to risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium-glucose cotransporter 2 inhibitor.

Chan YH, Chen SW, Chao TF, Kao YW, Huang CY, Chu PH
Background
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear.
Methods
We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first.
Results
The patients\' baseline body mass index (BMI) was 28.08 [Formula: see text] 4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35 [Formula: see text] 3.28 kg (1.78%[Formula: see text] 4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0-4.9% (n = 4814), and [Formula: see text] 5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI < 23 kg/m2, AF risk significantly increased in patients with baseline BMI [Formula: see text] 27.5 kg/m2 (P for trend = 0.015). Compared with those without BW loss after SGLT2i treatment, AF risk significantly decreased with a BW loss of [Formula: see text] 5.0% (adjusted hazard ratios [95% confidence intervals]: 0.39[0.22-0.68]). Use of diuretics, old age, high-dose SGLT2i, higher estimated glomerular filtration rate, and baseline BMI were independent factors associated with a BW loss of [Formula: see text] 5.0% following SGLT2i initiation. By contrast, neither baseline BMI nor BW loss after SGLT2i treatment predicted major cardiovascular adverse events or heart failure hospitalization risk (P for trend > 0.05).
Conclusion
BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.



Cardiovasc Diabetol: 29 Apr 2021; 20:93
Chan YH, Chen SW, Chao TF, Kao YW, Huang CY, Chu PH
Cardiovasc Diabetol: 29 Apr 2021; 20:93 | PMID: 33941171
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Abstract

From glucose lowering agents to disease/diabetes modifying drugs: a \"SIMPLE\" approach for the treatment of type 2 diabetes.

Mosenzon O, Del Prato S, Schechter M, Leiter LA, ... DeFronzo RA, Raz I
During the last decade we experienced a surge in the number of glucose lowering agents that can be used to treat patients with type 2 diabetes. Especially important are the discoveries that sodium glucose co-transporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve patients\' cardiovascular and renal outcomes. Accordingly, various medical associations have updated their guidelines for the treatment of diabetes in this new era. Though not agreeing on every issue, these position-statements generally share a detailed and often complex workflow that may be too complicated for the busy and overworked primary care setting, where the majority of patients with type 2 diabetes are managed in many countries. Other guidelines, generally those from the cardiology associations focus primarily on the population of patients with high risk for or pre-existing cardiovascular disease, which represent only the minority of patients with type 2 diabetes. We believe that we should re-define SGLT2i and GLP-1 RA as diabetes/disease modifying drugs (DMDs) given the recent evidence of their cardiovascular and renal benefits. Based on this definition we have designed a SIMPLE approach in order to assist primary care teams in selecting the most appropriate therapy for their patients. We believe that most subjects newly diagnosed with type 2 diabetes should initiate early combination therapy with metformin and a prognosis changing DMD. The decision whether to use GLP-1 RA or SGLT2i should be made based on specific patient\'s risk factors and preferences. Importantly, DMDs are known to have a generally safe side-effect profile, with lower risk for hypoglycemia and weight gain, further promoting their wider usage. Early combination therapy with DMDs may improve the multiple pathophysiological abnormalities responsible for type 2 diabetes and its complications, thus resulting in the greatest long term benefits.



Cardiovasc Diabetol: 27 Apr 2021; 20:92
Mosenzon O, Del Prato S, Schechter M, Leiter LA, ... DeFronzo RA, Raz I
Cardiovasc Diabetol: 27 Apr 2021; 20:92 | PMID: 33910583
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Abstract

SGLT2 inhibitors and lower limb complications: an updated meta-analysis.

Lin C, Zhu X, Cai X, Yang W, ... Nie L, Ji L
Background
To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.
Methods
Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.
Result
The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = - 0.461, 95% CI - 0.726 to - 0.197), PAD (β = - 0.359, 95% CI - 0.545 to - 0.172) and DF (β = - 0.476, 95% CI - 0.836 to - 0.116). Lower baseline diastolic blood pressure (β = - 0.528, 95% CI - 0.852 to - 0.205), more systolic blood pressure reduction (β = - 0.207, 95% CI - 0.390 to - 0.023) and more diastolic blood pressure reduction (β = - 0.312, 95% CI - 0.610 to - 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.
Conclusions
The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.



Cardiovasc Diabetol: 27 Apr 2021; 20:91
Lin C, Zhu X, Cai X, Yang W, ... Nie L, Ji L
Cardiovasc Diabetol: 27 Apr 2021; 20:91 | PMID: 33910574
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Abstract

Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system.

Herman-Edelstein M, Guetta T, Barnea A, Waldman M, ... Hochhauser E, Aravot D
Background
Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice.
Methods
Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested.
Results
ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment.
Conclusion
Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.



Cardiovasc Diabetol: 26 Apr 2021; 20:90
Herman-Edelstein M, Guetta T, Barnea A, Waldman M, ... Hochhauser E, Aravot D
Cardiovasc Diabetol: 26 Apr 2021; 20:90 | PMID: 33906662
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Abstract

Predictive value of visit-to-visit blood pressure variability for cardiovascular events in patients with coronary artery disease with and without diabetes mellitus.

Wong YK, Chan YH, Hai JSH, Lau KK, Tse HF
Background
High blood pressure is a major risk factor for cardiovascular disease. Visit-to-visit blood pressure variability (BPV) has recently been shown to predict cardiovascular outcomes. We investigated the predictive value of BPV for major adverse cardiovascular events (MACE) among patients with coronary artery disease (CAD), with and without type 2 diabetes mellitus (T2DM).
Methods
Patients with stable CAD were enrolled and monitored for new MACE. Visit-to-visit BPV was defined as the coefficient of variation (CV) of systolic and diastolic BP across clinic visits. Multivariable logistic regression analysis was performed to evaluate the association of BPV with MACE. Area under the receiver operating characteristic curve (AUC) was used to assess its predictive ability.
Results
Among 1140 Chinese patients with stable CAD, 192 (17%) experienced a new MACE. In multivariable analyses, the risk of MACE was significantly associated with CV of systolic BP (odds ratio [OR] for highest versus lowest quartile, 3.30; 95% CI 1.97-5.54), and diastolic BP (OR for highest versus lowest quartile, 2.39; 95% CI 1.39-4.11), after adjustment for variables of the risk factor model (age, gender, T2DM, hypertension, antihypertensive agents, number of BP measurements) and mean BP. The risk factor model had an AUC of 0.70 for prediction of MACE. Adding systolic/diastolic CV into the risk factor model with mean BP significantly increased the AUC to 0.73/0.72 (P = 0.002/0.007). In subgroup analyses, higher CV of systolic BP remained significantly associated with an increased risk for MACE in patients with and without T2DM, whereas the association of CV of diastolic BP with MACE was observed only in those without T2DM.
Conclusions
Visit-to-visit variability of systolic BP and of diastolic BP was an independent predictor of new MACE and provided incremental prognostic value beyond mean BP and conventional risk factors in patients with stable CAD. The association of BPV in CAD patients without T2DM with subsequent risk for MACE was stronger than in those with T2DM.



Cardiovasc Diabetol: 23 Apr 2021; 20:88
Wong YK, Chan YH, Hai JSH, Lau KK, Tse HF
Cardiovasc Diabetol: 23 Apr 2021; 20:88 | PMID: 33894788
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Abstract

Early and long-term prognosis in patients with and without type 2 diabetes after carotid intervention: a Swedish nationwide propensity score matched cohort study.

Zabala A, Gottsäter A, Lind M, Svensson AM, ... Nyström T, Jonsson M
Objectives
To investigate early and long-term outcomes after treatment of carotid artery stenosis in patients with type 2 diabetes (T2D) compared to patients without T2D.
Design/method
This observational nationwide population-based retrospective cohort study investigated all T2D patients treated for carotid stenosis registered in the National Swedish Vascular Surgery and the National Diabetes Registries. Data was collected prospectively for all patients after carotid intervention, during 2009-2015. We estimated crude early (within 30-days) hazard ratios (HRs) risk of stroke and death, and long-term HRs risk, adjusted for confounders with 95% confidence intervals (CIs), for stroke and death and major adverse cardiovascular events (MACE) by using inverse probability of treatment weighting matching.
Results
A total of 1341 patients with T2D and 4162 patients without T2D were included; 89% treated for symptomatic carotid stenosis, 96% with carotid endarterectomy. There was an increased early risk, HRs (95% CI), for stroke in T2D patients 1.65 (1.17-2.32), whereas risk for early death 1.00 (0.49-2.04) was similar in both groups. During a median follow-up of 4.3 (T2D) and 4.6 (without T2D), with a maximum of 8.0 years; after propensity score matching there was an increased HRs (95% CI) of stroke 1.27 (1.05-1.54) and death 1.27 (1.10-1.47) in T2D patients compared to patients without T2D. Corresponding numbers for MACE were 1.21 (1.08-1.35).
Conclusions
Patients with T2D run an increased risk for stroke, death, and MACE after carotid intervention. They also have an increased perioperative risk for stroke, but not for death.



Cardiovasc Diabetol: 23 Apr 2021; 20:85
Zabala A, Gottsäter A, Lind M, Svensson AM, ... Nyström T, Jonsson M
Cardiovasc Diabetol: 23 Apr 2021; 20:85 | PMID: 33894785
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Abstract

Effect of heart rate on left ventricular longitudinal myocardial function in type 2 diabetes mellitus.

Yamauchi Y, Tanaka H, Yokota S, Mochizuki Y, ... Ogawa W, Hirata KI
Background
Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain.
Methods
We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS < 18%.
Results
GLS in T2DM patients with high HR was significantly lower than that in T2DM patients with low HR (16.3% ± 4.2% vs. 17.8% ± 2.8%; P = 0.03), whereas GLS in normal subjects with high and low HR was similar (20.3 ± 1.7% vs. 20.3 ± 2.0%; P = 0.99). Multivariable logistic regression analysis showed that high HR (odds ratio: 1.04; 95% confidence interval: 1.01-1.07; P = 0.01) was independently associated with GLS < 18% in T2DM patients as well as HbA1c, T2DM duration, LVEF, body mass index, and mitral inflow E and mitral e\' annular velocity ratio. One sequential logistic model evaluating the associations between GLS < 18% and clinical variables in T2DM patients showed an improvement with the addition of LVEF and E/e\' (P < 0.001) and a further improvement with the addition of high HR (P < 0.001).
Conclusion
Compared with normal subjects, resting HR was associated with LV longitudinal myocardial function in asymptomatic T2DM patients with preserved LVEF. Our findings provide new insights on the management of T2DM patients.



Cardiovasc Diabetol: 23 Apr 2021; 20:87
Yamauchi Y, Tanaka H, Yokota S, Mochizuki Y, ... Ogawa W, Hirata KI
Cardiovasc Diabetol: 23 Apr 2021; 20:87 | PMID: 33894777
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Abstract

The risk trajectory of different cardiovascular morbidities associated with chronic kidney disease among patients with newly diagnosed diabetes mellitus: a propensity score-matched cohort analysis.

Chao CT, Lee SY, Wang J, Chien KL, Hung KY
Background
Chronic kidney disease (CKD) introduces an increased cardiovascular risk among patients with diabetes mellitus (DM). The risk and tempo of cardiovascular diseases may differ depending upon their type. Whether CKD differentially influences the risk of developing each cardiovascular morbidity in patients with newly diagnosed DM remains unexplored.
Methods
We identified patients with incident DM from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort (n = 429,616), and uncovered those developing CKD after DM and their propensity score-matched counterparts without. After follow-up, we examined the cardiovascular morbidity-free rates of patients with and without CKD after DM, followed by Cox proportional hazard regression analyses. We further evaluated the cumulative risk of developing each outcome consecutively during the study period.
Results
From LCDP, we identified 55,961 diabetic patients with CKD and matched controls without CKD. After 4.2 years, patients with incident DM and CKD afterward had a significantly higher risk of mortality (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.06-1.14), heart failure (HF) (HR 1.282, 95% CI 1.19-1.38), acute myocardial infarction (AMI) (HR 1.16, 95% CI 1.04-1.3), and peripheral vascular disease (PVD) (HR 1.277, 95% CI 1.08-1.52) compared to those without CKD. The CKD-associated risk of mortality, HF and AMI became significant soon after DM occurred and remained significant throughout follow-up, while the risk of PVD conferred by CKD did not emerge until 4 years later. The CKD-associated risk of ischemic, hemorrhagic stroke and atrial fibrillation remained insignificant.
Conclusions
The cardiovascular risk profile among incident DM patients differs depending on disease type. These findings can facilitate the selection of an optimal strategy for early cardiovascular care for newly diagnosed diabetic patients.



Cardiovasc Diabetol: 23 Apr 2021; 20:86
Chao CT, Lee SY, Wang J, Chien KL, Hung KY
Cardiovasc Diabetol: 23 Apr 2021; 20:86 | PMID: 33894776
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Impact:
Abstract

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus.

Fischer LT, Hochfellner DA, Knoll L, Pöttler T, Mader JK, Aberer F
Background
The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care.
Methods
A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months.
Results
We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events.
Conclusions
Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.



Cardiovasc Diabetol: 23 Apr 2021; 20:89
Fischer LT, Hochfellner DA, Knoll L, Pöttler T, Mader JK, Aberer F
Cardiovasc Diabetol: 23 Apr 2021; 20:89 | PMID: 33894772
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Impact:
Abstract

Prognostic value of NT-proBNP in patients with chronic coronary syndrome and normal left ventricular systolic function according to glucose status: a prospective cohort study.

Liu HH, Cao YX, Jin JL, Guo YL, ... Dong Q, Li JJ
Background
The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism.
Methods
A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status.
Results
Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34-4.91] or DM (HR: 2.34, 95% CI: 1.32-4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively.
Conclusions
The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.



Cardiovasc Diabetol: 21 Apr 2021; 20:84
Liu HH, Cao YX, Jin JL, Guo YL, ... Dong Q, Li JJ
Cardiovasc Diabetol: 21 Apr 2021; 20:84 | PMID: 33888145
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Impact:
Abstract

Stronger association of triglyceride glucose index than the HOMA-IR with arterial stiffness in patients with type 2 diabetes: a real-world single-centre study.

Wang S, Shi J, Peng Y, Fang Q, ... Zhang Y, Wang W
Background
The triglyceride-glucose index (TyG index) has been proposed as a simple and reliable alternative insulin resistance (IR) marker, while the homeostasis model assessment for IR (HOMA-IR) is the most frequently used index. Few studies have evaluated the role of IR assessed by the TyG index and HOMA-IR on arterial stiffness in a type 2 diabetes (T2D) population with a high risk of increased arterial stiffness. We aimed to investigate the association of the TyG index and HOMA-IR with arterial stiffness in patients with T2D.
Methods
We recruited 3185 patients with T2D, who underwent brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, but without previous cardiovascular disease. Increased arterial stiffness was defined as a baPWV value greater than the 75th percentile (18.15 m/s) in the present study. The TyG index was determined as ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and the HOMA-IR was calculated as (fasting insulin [μIU/mL] × fasting glucose [mmol/L])/22.5.
Results
The mean age of the study participants was 54.6 ± 12.0 years, and 1954 (61.4%) were men. Seemingly unrelated regression estimation analysis demonstrated that the TyG index had stronger associations with baPWV than the HOMA-IR (all P < 0.001). In the multivariable logistic analyses, each one-unit increase in the TyG index was associated with a 1.40-fold (95% CI 1.16-1.70, P < 0.001) higher prevalence of increased arterial stiffness, but the prominent association of the HOMA-IR with the prevalence of increased arterial stiffness was not observed. Subgroup analyses showed that a more significant association between the TyG index and the prevalence of increased arterial stiffness was detected in older patients with a longer duration of diabetes and poor glycaemic control (all P < 0.05).
Conclusions
Compared with the HOMA-IR, the TyG index is independently and more strongly associated with arterial stiffness in patients with T2D.



Cardiovasc Diabetol: 21 Apr 2021; 20:82
Wang S, Shi J, Peng Y, Fang Q, ... Zhang Y, Wang W
Cardiovasc Diabetol: 21 Apr 2021; 20:82 | PMID: 33888131
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Impact:
Abstract

Effects of sodium-glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta-analysis of randomized controlled trials.

Zheng C, Lin M, Chen Y, Xu H, Yan L, Dai H
Background
Controlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) are beneficial for the survival of patients with heart failure (HF). However, it is unclear whether SGLT-2i can provide benefit in patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the outcomes of cardiovascular, renal, and safety outcomes of SGLT-2i administration in patients with cardiovascular diseases.
Methods
We searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2i in patients with cardiovascular disease with or without diabetes. Primary outcomes were cardiovascular outcomes and renal outcomes. Secondary outcomes were safety outcomes, including adverse endocrine outcomes and adverse infection outcomes. The effects of SGLT-2i were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality.
Results
We identified 10 randomised controlled trials (25,108 patients in the SGLT-2i group and 18,574 patients in the placebo group). Meta-analysis revealed that SGLT-2i treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI] 0.81-0.91; P < 0.00001; I2 = 0%; cardiovascular mortality RR: 0.85; 95% CI 0.79-0.92; P < 0.0001; I2 = 26%; HHF RR: 0.69; 95% CI 0.64-0.81; P < 0.00001; I2 = 0%). In patients with HF, mortality and HHF after SGLT-2i treatment for HF with reduced ejection fraction were significantly reduced, whereas HF with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2i induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher.
Conclusions
SGLT-2i had significant clinical effects on cardiovascular outcomes and significantly influenced acute kidney injury. The effects of SGLT-2i on cardiovascular disease were independent of diabetic status. Sotagliflozin could have advantages over other SGLT-2i in lowering HHF.



Cardiovasc Diabetol: 21 Apr 2021; 20:83
Zheng C, Lin M, Chen Y, Xu H, Yan L, Dai H
Cardiovasc Diabetol: 21 Apr 2021; 20:83 | PMID: 33888126
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Impact:
Abstract

Are there sex differences in the effect of type 2 diabetes in the incidence and outcomes of myocardial infarction? A matched-pair analysis using hospital discharge data.

Lopez-de-Andres A, Jimenez-Garcia R, Hernández-Barrera V, de Miguel-Yanes JM, ... Lopez-Herranz M, de Miguel-Diez J
Background
To analyze incidence, use of therapeutic procedures, and in-hospital outcomes in patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) according to the presence of type 2 diabetes (T2DM) in Spain (2016-2018) and to investigate sex differences.
Methods
Using the Spanish National Hospital Discharge Database, we estimated the incidence of myocardial infarctions (MI) in men and women with and without T2DM aged ≥ 40 years. We analyzed comorbidity, procedures, and outcomes. We matched each man and woman with T2DM with a non-T2DM man and woman of identical age, MI code, and year of hospitalization. Propensity score matching was used to compare men and women with T2DM.
Results
MI was coded in 109,759 men and 44,589 women (30.47% with T2DM). The adjusted incidence of STEMI (IRR 2.32; 95% CI 2.28-2.36) and NSTEMI (IRR 2.91; 95% CI 2.88-2.94) was higher in T2DM than non-T2DM patients, with higher IRRs for NSTEMI in both sexes. The incidence of STEMI and NSTEMI was higher in men with T2DM than in women with T2DM. After matching, percutaneous coronary intervention (PCI) was less frequent among T2DM men than non-T2DM men who had STEMI and NSTEMI. Women with T2DM and STEMI less frequently had a code for PCI that matched that of non-T2DM women. In-hospital mortality (IHM) was higher among T2DM women with STEMI and NSTEMI than in matched non-T2DM women. In men, IHM was higher only for NSTEMI. Propensity score matching showed higher use of PCI and coronary artery bypass graft and lower IHM among men with T2DM than women with T2DM for both STEMI and NSTEMI.
Conclusions
T2DM is associated with a higher incidence of STEMI and NSTEMI in both sexes. Men with T2DM had higher incidence rates of STEMI and NSTEMI than women with T2DM. Having T2DM increased the risk of IHM after STEMI and NSTEMI among women and among men only for NSTEMI. PCI appears to be less frequently used in T2DM patients After STEMI and NSTEMI, women with T2DM less frequently undergo revascularization procedures and have a higher mortality risk than T2DM men.



Cardiovasc Diabetol: 21 Apr 2021; 20:81
Lopez-de-Andres A, Jimenez-Garcia R, Hernández-Barrera V, de Miguel-Yanes JM, ... Lopez-Herranz M, de Miguel-Diez J
Cardiovasc Diabetol: 21 Apr 2021; 20:81 | PMID: 33888124
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Impact:
Abstract

Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness.

Aroor AR, Mummidi S, Lopez-Alvarenga JC, Das N, ... Chandrasekar B, DeMarco VG
Objective
Cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes, and both serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy.
Methods
Sixteen-week-old male Zucker Obese rats (ZO; n = 64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg-1•day-1; ZOSV); Group 3: valsartan (31 mg•kg-1•day-1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg-1•day-1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage.
Results
Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val decreased aortic stiffness and reversed impairment in nitric oxide-induced vascular relaxation in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective than val in ameliorating DD. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, cytokine array revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val, suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val, but not val, increased IL-4, which is increasingly recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity-associated DD.
Conclusions
These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.



Cardiovasc Diabetol: 20 Apr 2021; 20:80
Aroor AR, Mummidi S, Lopez-Alvarenga JC, Das N, ... Chandrasekar B, DeMarco VG
Cardiovasc Diabetol: 20 Apr 2021; 20:80 | PMID: 33882908
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Impact:
Abstract

Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients.

Xiang B, Zhao X, Zhou X
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were developed as antidiabetic agents, but accumulating evidence has shown their beneficial effects on the cardiovascular system. Analyses of the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggested that these benefits are independent of glycemic control. Several large-scale outcome trials of SGLT2i also showed cardiovascular benefits in nondiabetic patients, strengthening this perspective. Extensive animal and clinical studies have likewise shown that mechanisms other than the antihyperglycemic effect underlie the cardiovascular benefits. Recent clinical guidelines recommend the use of SGLT2i in patients with type 2 diabetes mellitus and cardiovascular diseases because of the proven cardiovascular protective effects. Since the cardiovascular benefits are independent of glycemic control, the therapeutic spectrum of SGLT2i will likely be extended to nondiabetic patients.



Cardiovasc Diabetol: 06 Apr 2021; 20:78
Xiang B, Zhao X, Zhou X
Cardiovasc Diabetol: 06 Apr 2021; 20:78 | PMID: 33827579
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Impact:
Abstract

PAR-4/Ca-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes.

Giannella A, Ceolotto G, Radu CM, Cattelan A, ... Avogaro A, Vigili de Kreutzenberg S
Background
Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages.
Methods
In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages.
Results
We found that MPs CD62P+ (PMP) and CD142+ (tissue factor-bearing MP) were significantly higher in PGC T2DM than GGC T2DM and NGT. Among MPs, PMP were also correlated with HbA1c and IL-6. In vitro, we showed that acute thrombin exposure stimulated a significantly higher PMP release in PGC T2DM than GGC T2DM through a more robust activation of PAR-4 receptor than PAR-1 receptor. Treatment with PAR-4 agonist induced an increased release of PMP in PGC with a Ca2+-calpain dependent mechanism since this effect was blunted by calpain inhibitor. Finally, the uptake of PMP derived from PAR-4 treated PGC platelets into THP-1 transformed macrophages promoted a marked increase of IL-6 release compared to PMP derived from GGC through the activation of the NF-kB pathway.
Conclusions
These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.



Cardiovasc Diabetol: 02 Apr 2021; 20:77
Giannella A, Ceolotto G, Radu CM, Cattelan A, ... Avogaro A, Vigili de Kreutzenberg S
Cardiovasc Diabetol: 02 Apr 2021; 20:77 | PMID: 33812377
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Impact:
Abstract

Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies.

Ding X, Wang X, Wu J, Zhang M, Cui M
Background
Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride-glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis.
Methods
Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results.
Results
Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29-2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18-1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47-2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23-1.29, I2 = 0%, P < 0.001).
Conclusions
A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline.



Cardiovasc Diabetol: 02 Apr 2021; 20:76
Ding X, Wang X, Wu J, Zhang M, Cui M
Cardiovasc Diabetol: 02 Apr 2021; 20:76 | PMID: 33812373
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Impact:
Abstract

Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial.

Sposito AC, Breder I, Soares AAS, Kimura-Medorima ST, ... Quinaglia T, ADDENDA-BHS2 trial investigators
Background
The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy.
Methods
In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R).
Results
Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments.
Conclusions
Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.



Cardiovasc Diabetol: 25 Mar 2021; 20:74
Sposito AC, Breder I, Soares AAS, Kimura-Medorima ST, ... Quinaglia T, ADDENDA-BHS2 trial investigators
Cardiovasc Diabetol: 25 Mar 2021; 20:74 | PMID: 33771149
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Impact:
Abstract

Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study.

Yubero-Serrano EM, Alcalá-Diaz JF, Gutierrez-Mariscal FM, Arenas-de Larriva AP, ... Gómez-Coronado D, Lopez-Miranda J
Background
Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association.
Methods
CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants\' apoB-depleted plasma was performed.
Results
The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment.
Conclusions
Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.



Cardiovasc Diabetol: 24 Mar 2021; 20:72
Yubero-Serrano EM, Alcalá-Diaz JF, Gutierrez-Mariscal FM, Arenas-de Larriva AP, ... Gómez-Coronado D, Lopez-Miranda J
Cardiovasc Diabetol: 24 Mar 2021; 20:72 | PMID: 33766036
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Impact:
Abstract

Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population-based cohort study.

Cheung CL, Sing CW, Lau WCY, Li GHY, ... Chan EWY, Wong ICK
Background
Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients.
Methods
Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID).
Results
There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21-1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56-0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were - 2.06% (95% CI - 4.08 to 0.16%); - 3.06% (95% CI - 4.79 to - 1.15%); and - 1.8% (- 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban.
Conclusions
Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.



Cardiovasc Diabetol: 24 Mar 2021; 20:71
Cheung CL, Sing CW, Lau WCY, Li GHY, ... Chan EWY, Wong ICK
Cardiovasc Diabetol: 24 Mar 2021; 20:71 | PMID: 33766030
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Impact:
Abstract

Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance.

Yan WF, Gao Y, Zhang Y, Guo YK, ... Li Y, Yang ZG
Background
Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR).
Methods
A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters.
Results
PFR and PFR/EDV decreased from the control group, through HTN(T2DM -), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM -) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM -) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = - 0.756 ~ 0.795).
Conclusions
T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.



Cardiovasc Diabetol: 24 Mar 2021; 20:73
Yan WF, Gao Y, Zhang Y, Guo YK, ... Li Y, Yang ZG
Cardiovasc Diabetol: 24 Mar 2021; 20:73 | PMID: 33766020
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Impact:
Abstract

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension.

Naguib YM, Samaka RM, Rizk MS, Ameen O, Motawea SM
Background
The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model.
Methods
Thirty male Wistar rats weighing 150-200 g were equally divided into: 1-Control group (fed normal laboratory diet for 24 weeks), 2-Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3-Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies.
Results
High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions.
Conclusion
Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.



Cardiovasc Diabetol: 23 Mar 2021; 20:70
Naguib YM, Samaka RM, Rizk MS, Ameen O, Motawea SM
Cardiovasc Diabetol: 23 Mar 2021; 20:70 | PMID: 33761942
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Impact:
Abstract

Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study.

Lugner M, Sattar N, Miftaraj M, Ekelund J, ... Svensson AM, Eliasson B
Background
Major prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes.
Methods
We linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models.
Results
We identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2 in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61-1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99-2.08) and 1.68 (95% CI 1.04-2.72), respectively.
Conclusions
This observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.



Cardiovasc Diabetol: 21 Mar 2021; 20:67
Lugner M, Sattar N, Miftaraj M, Ekelund J, ... Svensson AM, Eliasson B
Cardiovasc Diabetol: 21 Mar 2021; 20:67 | PMID: 33752680
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Impact:
Abstract

Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project.

Sinha A, Ning H, Ahmad FS, Bancks MP, ... Lloyd-Jones DM, Khan SS
Background
Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG).
Methods
Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan-Meier analysis, Cox models adjusted for the competing risk of death, and Irwin\'s restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40-59 years) and older (60-79 years) adults with FPG < 100 mg/dL, prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) across race-sex groups.
Results
In 40,117 participants with 638,910 person-years of follow-up, 4846 cases of incident HF occurred. The lifetime risk of HF was significantly higher among middle-aged White adults and Black women with prediabetes (range: 6.1% [95% CI 4.8%, 7.4%] to 10.8% [95% CI 8.3%, 13.4%]) compared with normoglycemic adults (range: 3.5% [95% CI 3.0%, 4.1%] to 6.5% [95% CI 4.9%, 8.1%]). Middle-aged Black women with diabetes had the highest lifetime risk (32.4% [95% CI 26.0%, 38.7%]) and aHR (4.0 [95% CI 3.0, 5.4]) for HF across race-sex groups. Middle-aged adults with prediabetes and diabetes lived on average 0.9-1.6 and 4.1-6.0 fewer years free from HF, respectively. Findings were similar in older adults except older Black women with prediabetes did not have a higher lifetime risk of HF.
Conclusions
Prediabetes was associated with higher lifetime risk of HF in middle-aged White adults and Black women, with the association attenuating in older Black women. Black women with diabetes had the highest lifetime risk of HF compared with other race-sex groups.



Cardiovasc Diabetol: 21 Mar 2021; 20:66
Sinha A, Ning H, Ahmad FS, Bancks MP, ... Lloyd-Jones DM, Khan SS
Cardiovasc Diabetol: 21 Mar 2021; 20:66 | PMID: 33752676
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Impact:
Abstract

The prediction of Metabolic Syndrome alterations is improved by combining waist circumference and handgrip strength measurements compared to either alone.

Lopez-Lopez JP, Cohen DD, Ney-Salazar D, Martinez D, ... Yusuf S, Lopez-Jaramillo P
Background
Adiposity is a major component of the metabolic syndrome (MetS), low muscle strength has also been identified as a risk factor for MetS and for cardiovascular disease. We describe the prevalence of MetS and evaluate the relationship between muscle strength, anthropometric measures of adiposity, and associations with the cluster of the components of MetS, in a middle-income country.
Methods
MetS was defined by the International Diabetes Federation criteria. To assess the association between anthropometric variables (waist circumference (WC), waist-to-hip ratio (W/H), body mass index (BMI)), strength (handgrip/kg bodyweight (HGS/BW)) and the cluster of MetS, we created a MetS score. For each alteration (high triglycerides, low HDLc, dysglycemia, or high blood pressure) one point was conferred. To evaluate the association an index of fat:muscle and MetS score, participants were divided into 9 groups based on combinations of sex-specific tertiles of WC and HGS/BW.
Results
The overall prevalence of MetS in the 5,026 participants (64% women; mean age 51.2 years) was 42%. Lower HGS/BW, and higher WC, BMI, and W/H were associated with a higher MetS score. Amongst the 9 HGS/BW:WC groups, participants in the lowest tertile of HGS/BW and the highest tertile of WC had a higher MetS score (OR = 4.69 in women and OR = 8.25 in men;p < 0.01) compared to those in the highest tertile of HGS/BW and in the lowest tertile of WC.
Conclusion
WC was the principal risk factor for a high MetS score and an inverse association between HGS/BW and MetS score was found. Combining these anthropometric measures improved the prediction of metabolic alterations over either alone.



Cardiovasc Diabetol: 21 Mar 2021; 20:68
Lopez-Lopez JP, Cohen DD, Ney-Salazar D, Martinez D, ... Yusuf S, Lopez-Jaramillo P
Cardiovasc Diabetol: 21 Mar 2021; 20:68 | PMID: 33752666
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Impact:
Abstract

Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: protective effect of gliflozins.

Park SH, Belcastro E, Hasan H, Matsushita K, ... Morel O, Schini-Kerth VB
Background
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced cardiovascular risk in type 2 diabetes patients independently of glycemic control. Although angiotensin II (Ang II) and blood-derived microparticles are major mediators of cardiovascular disease, their impact on SGLT1 and 2 expression and function in endothelial cells (ECs) and isolated arteries remains unclear.
Methods
ECs were isolated from porcine coronary arteries, and arterial segments from rats. The protein expression level was assessed by Western blot analysis and immunofluorescence staining, mRNA levels by RT-PCR, oxidative stress using dihydroethidium, nitric oxide using DAF-FM diacetate, senescence by senescence-associated beta-galactosidase activity, and platelet aggregation by aggregometer. Microparticles were collected from blood of patients with coronary artery disease (CAD-MPs).
Results
Ang II up-regulated SGLT1 and 2 protein levels in ECs, and caused a sustained extracellular glucose- and Na+-dependent pro-oxidant response that was inhibited by the NADPH oxidase inhibitor VAS-2780, the AT1R antagonist losartan, sotagliflozin (Sota, SGLT1 and SGLT2 inhibitor), and empagliflozin (Empa, SGLT2 inhibitor). Ang II increased senescence-associated beta-galactosidase activity and markers, VCAM-1, MCP-1, tissue factor, ACE, and AT1R, and down-regulated eNOS and NO formation, which were inhibited by Sota and Empa. Increased SGLT1 and SGLT2 protein levels were observed in the rat aortic arch, and Ang II- and eNOS inhibitor-treated thoracic aorta segments, and were associated with enhanced levels of oxidative stress and prevented by VAS-2780, losartan, Sota and Empa. CAD-MPs promoted increased levels of SGLT1, SGLT2 and VCAM-1, and decreased eNOS and NO formation in ECs, which were inhibited by VAS-2780, losartan, Sota and Empa.
Conclusions
Ang II up-regulates SGLT1 and 2 protein expression in ECs and arterial segments to promote sustained oxidative stress, senescence and dysfunction. Such a sequence contributes to CAD-MPs-induced endothelial dysfunction. Since AT1R/NADPH oxidase/SGLT1 and 2 pathways promote endothelial dysfunction, inhibition of SGLT1 and/or 2 appears as an attractive strategy to enhance the protective endothelial function.



Cardiovasc Diabetol: 15 Mar 2021; 20:65
Park SH, Belcastro E, Hasan H, Matsushita K, ... Morel O, Schini-Kerth VB
Cardiovasc Diabetol: 15 Mar 2021; 20:65 | PMID: 33726768
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Impact:
Abstract

Cost-effectiveness of screening of coronary artery disease in patients with type 2 DIABetes at a very high cardiovascular risk (SCADIAB study) rational and design.

Mohammedi K, Préaubert N, Cariou T, Rigalleau V, ... Bezin J, Benard A
Background
Screening for coronary artery disease (CAD) remains broadly performed in patients with type 2 diabetes (T2DM), although the lack of evidence. We conduct a real-world evidence (RWE) study to assess the risk of major clinical outcomes and economic impact of routine CAD screening in T2DM individuals at a very high cardiovascular risk.
Methods
SCADIAB is a comparative nationwide cohort study using data from the French National Health Data System. The main inclusion criteria are: age ≥ 40 years, DT2 diagnosed for ≥ 7 years, with ≥ 2 additional cardiovascular risk factors plus a history of microvascular or macrovascular disease, except CAD. We estimated ≥ 90,000 eligible participants for our study. Data will be extracted from 01/01/2008 to 31/12/2019. Eligible participants will be identified during a first 7-year selection period (2008-2015). Each participant will be assigned either in experimental (CAD screening procedure during the selection period) or control group (no CAD screening) on 01/01/2015, and followed for 5 years. The primary endpoint is the incremental cost per life year saved over 5 years in CAD screening group versus no CAD screening. The main secondary endpoints are: total 5-year direct costs of each strategy; incidence of major cardiovascular (acute coronary syndrome, hospitalization for heart failure, coronary revascularization or all-cause death), cerebrovascular (hospitalization for transient ischemic attack, stroke, or carotid revascularization) and lower-limb events (peripheral artery disease, ischemic diabetic foot, lower-limb revascularization or amputation); and the budget impact for the French Insurance system to promote the cost-effective strategy. Analyses will be adjusted for a high-dimension propensity score taking into account known and unknown confounders. SCADIAB has been funded by the French Ministry of Health and the protocol has been approved by the French ethic authorities. Data management and analyses will start in the second half of 2021.
Discussion
SCADIAB is a large and contemporary RWE study that will assess the economic and clinical impacts of routine CAD screening in T2DM people at a very high cardiovascular risk. It will also evaluate the clinical practice regarding CAD screening and help to make future recommendations and optimize the use of health care resources. Trial registration ClinicalTrials.gov Identifier: NCT04534530 ( https://clinicaltrials.gov/ct2/show/NCT04534530 ).



Cardiovasc Diabetol: 12 Mar 2021; 20:63
Mohammedi K, Préaubert N, Cariou T, Rigalleau V, ... Bezin J, Benard A
Cardiovasc Diabetol: 12 Mar 2021; 20:63 | PMID: 33714278
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Impact:
Abstract

Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.

Chen S, Shen Y, Liu YH, Dai Y, ... Lu L, Ding FH
Background
We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM).
Methods
In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c).
Results
The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056-0.915, P = 0.037), Gensini score (β =  - 0.470, P < 0.001) and SYNTAX score (β =  - 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05).
Conclusion
Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.



Cardiovasc Diabetol: 12 Mar 2021; 20:64
Chen S, Shen Y, Liu YH, Dai Y, ... Lu L, Ding FH
Cardiovasc Diabetol: 12 Mar 2021; 20:64 | PMID: 33714276
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Impact:
Abstract

Association between physical activity level and cardiovascular risk factors in adolescents living with type 1 diabetes mellitus: a cross-sectional study.

Wu N, Bredin SSD, Jamnik VK, Koehle MS, ... Li J, Warburton DER
Background
Type 1 diabetes mellitus (T1DM) is associated with an increased risk for cardiovascular disease (CVD) related morbidity and premature mortality. Regular physical activity plays an important role in the primary and secondary prevention of CVD, improving overall health and wellbeing. Previous observational studies have examined the associations between self-reported physical activity and CVD risk factors in largely adult Caucasian populations. However, limited work has evaluated the relationship between objectively measured physical activity and CVD risk factors in other ethnicities, particularly Chinese youth living with T1DM.
Methods
This cross-sectional study assessed CVD risk factors, physical activity, and aerobic fitness (and their associations) in Chinese youth living with T1DM (n = 48) and peers (n = 19) without T1DM. Primary outcomes included blood pressure, lipid profiles, and physical activity (accelerometry). Statistical differences between groups were determined with chi-square, independent-samples t-tests, or analysis of covariance. The associations between aerobic fitness, daily physical activity variables, and CVD risk factors were assessed with univariate and multivariate linear regression analyses.
Results
Results were summarized using means and standard deviation (SD) for normally distributed variables and medians and 25-75th quartile for non-normally distributed variables. In comparison to peers without diabetes, youth living with T1DM showed higher levels of total cholesterol (3.14 ± 0.67 vs. 4.03 ± 0.81 mmol·L-1, p = 0.001), low-density lipoprotein cholesterol (1.74 ± 0.38 vs. 2.31 ± 0.72 mmol·L-1, p = 0.005), and triglycerides (0.60 ± 0.40 vs. 0.89 ± 0.31 mmol·L-1 p = 0.012), and lower maximal oxygen power (44.43 ± 8.29 vs. 35.48 ± 8.72 mL·kg-1·min-1, p = 0.003), total physical activity counts (451.01 ± 133.52 vs. 346.87 ± 101.97 counts·min-1, p = 0.004), metabolic equivalents (METs) (2.41 ± 0.60 vs. 2.09 ± 0.41 METs, p = 0.033), moderate-to-vigorous intensity physical activity [MVPA: 89.57 (61.00-124.14) vs (53.19 (35.68-63.16) min, p = 0.001], and the percentage of time spent in MVPA [11.91 (7.74-16.22) vs 8.56 (6.18-10.12) %, p = 0.038]. The level of high-density lipoprotein cholesterol was positively associated with METs (β = 0.29, p = 0.030, model R2 = 0.168), and the level of triglycerides was negatively associated with physical activity counts (β = - 0.001, p = 0.018, model R2 = 0.205) and METs (β = - 0.359, p = 0.015, model R2 = 0.208), and positively associated with time spent in sedentary behaviour (β = 0.002, p = 0.041, model R2 = 0.156) in persons living with T1DM.
Conclusions
Chinese youth with T1DM, despite their young age and short duration of diabetes, present early signs of CVD risk, as well as low physical activity levels and cardiorespiratory fitness compared to apparently healthy peers without diabetes. Regular physical activity is associated with a beneficial cardiovascular profile in T1DM, including improvements in lipid profile. Thus, physical activity participation should be widely promoted in youth living with T1DM.



Cardiovasc Diabetol: 11 Mar 2021; 20:62
Wu N, Bredin SSD, Jamnik VK, Koehle MS, ... Li J, Warburton DER
Cardiovasc Diabetol: 11 Mar 2021; 20:62 | PMID: 33712025
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Impact:
Abstract

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects.

Succurro E, Miceli S, Fiorentino TV, Sciacqua A, ... Andreozzi F, Sesti G
Background
Women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than their male counterparts. However, whether the risk for CVD is higher in prediabetic women than men is still debated. We aimed to determine whether sex-related differences exist in left ventricular mass index (LVMI), and myocardial mechano-energetic efficiency (MEEi) in with normal glucose tolerant (NGT), pre-diabetic and newly diagnosed type 2 diabetic subjects.
Methods
Sex-related differences in LVMI and myocardial MEEi, assessed by validated echocardiography-derived measures, were examined among 1562 adults with NGT, prediabetes, and newly diagnosed T2DM, defined according to fasting glucose, 2-h post-load glucose, or HbA1c.
Results
Worsening of glucose tolerance in both men and women was associated with an increase in age-adjusted LVMI and myocardial MEEi. Women with newly diagnosed T2DM exhibited greater relative differences in LVMI and myocardial MEEi than diabetic men when compared with their NGT counterparts. Prediabetic women exhibited greater relative differences in myocardial MEEi, but not in LVMI, than prediabetic men when compared with their NGT counterparts. The statistical test for interaction between sex and glucose tolerance on both LVMI (P < 0.0001), and myocardial MEEi (P < 0.0001) was significant suggesting a sex-specific association.
Conclusions
Left ventricle is subject to maladaptive changes with worsening of glucose tolerance, especially in women with newly diagnosed T2DM. The sex-specific increase in LVM and decrease in MEEi, both being predictors of CVD, may have a role in explaining the stronger impact of T2DM on the excess risk of CVD in women than in men.



Cardiovasc Diabetol: 05 Mar 2021; 20:60
Succurro E, Miceli S, Fiorentino TV, Sciacqua A, ... Andreozzi F, Sesti G
Cardiovasc Diabetol: 05 Mar 2021; 20:60 | PMID: 33676510
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Impact:
Abstract

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study.

Pintaudi B, Scatena A, Piscitelli G, Frison V, ... Di Bartolo P, Nicolucci A
Background
The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors.
Methods
The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated.
Results
Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased.
Conclusions
A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.



Cardiovasc Diabetol: 05 Mar 2021; 20:59
Pintaudi B, Scatena A, Piscitelli G, Frison V, ... Di Bartolo P, Nicolucci A
Cardiovasc Diabetol: 05 Mar 2021; 20:59 | PMID: 33676499
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Impact:
Abstract

Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease.

Hubbard D, Colantonio LD, Rosenson RS, Brown TM, ... Farkouh ME, Muntner P
Background
Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI).
Methods
We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events.
Results
Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90-0.95), 0.89 (95%CI: 0.85-0.93), and 1.18 (95%CI: 1.14-1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively.
Conclusion
Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.



Cardiovasc Diabetol: 28 Feb 2021; 20:58
Hubbard D, Colantonio LD, Rosenson RS, Brown TM, ... Farkouh ME, Muntner P
Cardiovasc Diabetol: 28 Feb 2021; 20:58 | PMID: 33648518
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Impact:
Abstract

Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study.

Gaborit B, Ancel P, Abdullah AE, Maurice F, ... Kober F, Dutour A
Background
Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D).
Methods
C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation-myocardial fat (primary endpoint) and liver fat content (LFC)-were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks.
Results
In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (- 2.6 kg [- 1.2; - 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (- 27 ± 23 vs. - 2 ± 24%, p = 0.0005) and visceral fat (- 7.8% [- 15.3; - 5.6] vs. - 0.1% [- 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups).
Conclusions
EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336.



Cardiovasc Diabetol: 28 Feb 2021; 20:57
Gaborit B, Ancel P, Abdullah AE, Maurice F, ... Kober F, Dutour A
Cardiovasc Diabetol: 28 Feb 2021; 20:57 | PMID: 33648515
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Impact:
Abstract

MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics.

Jakubik D, Fitas A, Eyileten C, Jarosz-Popek J, ... De Rosa S, Postula M
The epidemic of diabetes mellitus (DM) necessitates the development of novel therapeutic and preventative strategies to attenuate complications of this debilitating disease. Diabetic cardiomyopathy (DCM) is a frequent disorder affecting individuals diagnosed with DM characterized by left ventricular hypertrophy, diastolic and systolic dysfunction and myocardial fibrosis in the absence of other heart diseases. Progression of DCM is associated with impaired cardiac insulin metabolic signaling, increased oxidative stress, impaired mitochondrial and cardiomyocyte calcium metabolism, and inflammation. Various non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as well as their target genes are implicated in the complex pathophysiology of DCM. It has been demonstrated that miRNAs and lncRNAs play an important role in maintaining homeostasis through regulation of multiple genes, thus they attract substantial scientific interest as biomarkers for diagnosis, prognosis and as a potential therapeutic strategy in DM complications. This article will review the different miRNAs and lncRNA studied in the context of DM, including type 1 and type 2 diabetes and the contribution of pathophysiological mechanisms including inflammatory response, oxidative stress, apoptosis, hypertrophy and fibrosis to the development of DCM .



Cardiovasc Diabetol: 26 Feb 2021; 20:55
Jakubik D, Fitas A, Eyileten C, Jarosz-Popek J, ... De Rosa S, Postula M
Cardiovasc Diabetol: 26 Feb 2021; 20:55 | PMID: 33639953
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Impact:
Abstract

Traditional and non-traditional risk factors for peripheral artery disease development/progression in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

Cardoso CRL, Melo JV, Santos TRM, Leite NC, Salles GF
Background
The prognostic importance of non-traditional risk factors for peripheral artery disease (PAD) development/progression is scarcely studied in diabetes. We investigated if carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) added prognostic information beyond traditional cardiovascular risk markers for PAD outcomes.
Methods
Ankle-brachial index (ABI) was measured at baseline and after a median of 91 months of follow-up in 681 individuals with type 2 diabetes. Multivariate Cox regressions examined the associations between the candidate variables and the outcome. PAD development/progression was defined by a reduction in ABI ≥ 0.15 (to a level < 0.9) or limb revascularization procedures, lower-extremity amputations or death due to PAD. The improvement in risk discrimination was assessed by increases in C-statistics of the models.
Results
Seventy-seven patients developed/progressed PAD: 50 reduced ABI to < 0.9, seven had lower-limb revascularizations, and 20 had amputations or death. Age, male sex, diabetes duration, presence of microvascular complications (peripheral neuropathy and diabetic kidney disease), baseline HbA1c, 24-h systolic BP (SBP) and mean cumulative office SBP and LDL-cholesterol were associated with PAD development/progression in several models. CIMT and cf-PWV were additionally associated with PAD outcomes, and their inclusion further improved risk discrimination (with C-statistic increases between 0.025 and 0.030). The inclusion of ambulatory 24-h SBP, instead of office SBP, also improved PAD risk discrimination.
Conclusions
Increased CIMT and aortic stiffness are associated with greater risks of developing/progressing PAD, beyond traditional risk factors, in type 2 diabetes.



Cardiovasc Diabetol: 26 Feb 2021; 20:54
Cardoso CRL, Melo JV, Santos TRM, Leite NC, Salles GF
Cardiovasc Diabetol: 26 Feb 2021; 20:54 | PMID: 33639945
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Impact:
Abstract

Clinical and metabolomic predictors of regression to normoglycemia in a population at intermediate cardiometabolic risk.

Sevilla-González MDR, Merino J, Moreno-Macias H, Rojas-Martínez R, Gómez-Velasco DV, Manning AK
Background
Impaired fasting glucose (IFG) is a prevalent and potentially reversible intermediate stage leading to type 2 diabetes that increases risk for cardiometabolic complications. The identification of clinical and molecular factors associated with the reversal, or regression, from IFG to a normoglycemia state would enable more efficient cardiovascular risk reduction strategies. The aim of this study was to identify clinical and biological predictors of regression to normoglycemia in a non-European population characterized by high rates of type 2 diabetes.
Methods
We conducted a prospective, population-based study among 9637 Mexican individuals using clinical features and plasma metabolites. Among them, 491 subjects were classified as IFG, defined as fasting glucose between 100 and 125 mg/dL at baseline. Regression to normoglycemia was defined by fasting glucose less than 100 mg/dL in the follow-up visit. Plasma metabolites were profiled by Nuclear Magnetic Resonance. Multivariable cox regression models were used to examine the associations of clinical and metabolomic factors with regression to normoglycemia. We assessed the predictive capability of models that included clinical factors alone and models that included clinical factors and prioritized metabolites.
Results
During a median follow-up period of 2.5 years, 22.6% of participants (n = 111) regressed to normoglycemia, and 29.5% progressed to type 2 diabetes (n = 145). The multivariate adjusted relative risk of regression to normoglycemia was 1.10 (95% confidence interval [CI] 1.25 to 1.32) per 10 years of age increase, 0.94 (95% CI 0.91-0.98) per 1 SD increase in BMI, and 0.91 (95% CI 0.88-0.95) per 1 SD increase in fasting glucose. A model including information from age, fasting glucose, and BMI showed a good prediction of regression to normoglycemia (AUC = 0.73 (95% CI 0.66-0.78). The improvement after adding information from prioritized metabolites (TG in large HDL, albumin, and citrate) was non-significant (AUC = 0.74 (95% CI 0.68-0.80), p value = 0.485).
Conclusion
In individuals with IFG, information from three clinical variables easily obtained in the clinical setting showed a good prediction of regression to normoglycemia beyond metabolomic features. Our findings can serve to inform and design future cardiovascular prevention strategies.



Cardiovasc Diabetol: 26 Feb 2021; 20:56
Sevilla-González MDR, Merino J, Moreno-Macias H, Rojas-Martínez R, Gómez-Velasco DV, Manning AK
Cardiovasc Diabetol: 26 Feb 2021; 20:56 | PMID: 33639941
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Impact:
Abstract

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin.

Coleman CI, Costa OS, Brescia CW, Vardar B, Abdelgawwad K, Sood N
Background
Diabetes increases a patient\'s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes.
Methods
This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression.
Results
We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88-0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86-0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66-1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89-0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55-0.72).
Conclusions
In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.



Cardiovasc Diabetol: 25 Feb 2021; 20:52
Coleman CI, Costa OS, Brescia CW, Vardar B, Abdelgawwad K, Sood N
Cardiovasc Diabetol: 25 Feb 2021; 20:52 | PMID: 33637082
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Impact:
Abstract

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Saw EL, Pearson JT, Schwenke DO, Munasinghe PE, ... Fronius M, Katare R
Background
Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (M2AChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism. Impairment of these functions are hallmarks of diabetic heart disease (DHD). The role of the NNCS in DHD is unknown. The aim of this study was to examine the effect of diabetes on cardiac NNCS and determine if activation of cardiac NNCS is beneficial to the diabetic heart.
Methods
Ventricular samples from type-2 diabetic humans and db/db mice were used to measure the expression pattern of NNCS components (ChAT, CHT1, VAChT, AChE and M2AChR) and glucose transporter-4 (GLUT-4) by western blot analysis. To determine the function of the cardiac NNCS in the diabetic heart, a db/db mouse model with cardiac-specific overexpression of ChAT gene was generated (db/db-ChAT-tg). Animals were followed up serially and samples collected at different time points for molecular and histological analysis of cardiac NNCS components and prosurvival and proangiogenic signaling pathways.
Results
Immunoblot analysis revealed alterations in the components of cardiac NNCS and GLUT-4 in the type-2 diabetic human and db/db mouse hearts. Interestingly, the dysregulation of cardiac NNCS was followed by the downregulation of GLUT-4 in the db/db mouse heart. Db/db-ChAT-tg mice exhibited preserved cardiac and vascular function in comparison to db/db mice. The improved function was associated with increased cardiac ACh and glucose content, sustained angiogenesis and reduced fibrosis. These beneficial effects were associated with upregulation of the PI3K/Akt/HIF1α signaling pathway, and increased expression of its downstream targets-GLUT-4 and VEGF-A.
Conclusion
We provide the first evidence for dysregulation of the cardiac NNCS in DHD. Increased cardiac ACh is beneficial and a potential new therapeutic strategy to prevent or delay the development of DHD.



Cardiovasc Diabetol: 21 Feb 2021; 20:50
Saw EL, Pearson JT, Schwenke DO, Munasinghe PE, ... Fronius M, Katare R
Cardiovasc Diabetol: 21 Feb 2021; 20:50 | PMID: 33618724
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Impact:
Abstract

Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus.

Li M, Duan L, Cai Y, Hao B, ... Li H, Liu H
Background
Soluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of sST2 in patients with established CAD and its predictive value in CAD patients with and without type 2 diabetes mellitus (T2DM).
Methods
A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between sST2 and outcomes was investigated using multivariable Cox regression.
Results
During a median follow-up of 6.4 years, MACEs occurred in 775 patients, and 275 patients died. Multiple Cox regression models showed that a higher level of sST2 was an independent predictor of MACEs development (HR = 1.36, 95% CI 1.17-1.56, p < 0.001) and all-cause death (HR = 2.01, 95% CI 1.56-2.59, p < 0.001). The addition of sST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-index, net reclassification index, and integrated discrimination improvement, all p < 0.05). In subgroup analysis depending on diabetes status, the diabetes group had a significantly higher level of sST2, which remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models. The area under the curve (AUC) of CAD patients with diabetes mellitus was significantly higher than that of those without T2DM. For MACEs, the AUC was 0.737 (patients with T2DM) vs 0.620 (patients without T2DM). For all-cause death, the AUC was 0.923 (patients with T2DM) vs 0.789 (patients without T2DM).
Conclusions
A higher level of sST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. sST2 has strong predictive value for cardiovascular adverse events in CAD patients with T2DM, and these results provide new evidence for the role of sST2.



Cardiovasc Diabetol: 18 Feb 2021; 20:49
Li M, Duan L, Cai Y, Hao B, ... Li H, Liu H
Cardiovasc Diabetol: 18 Feb 2021; 20:49 | PMID: 33608010
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Impact:
Abstract

Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort.

Lejeune S, Roy C, Slimani A, Pasquet A, ... Beauloye C, Pouleur AC
Background
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The presence of diabetes might identify an important phenotype, with implications for therapeutic strategies. While diabetes is associated with worse prognosis in HFpEF, the prognostic impact of glycemic control is yet unknown. Hence, we investigated phenotypic differences between diabetic and non-diabetic HFpEF patients (pts), and the prognostic impact of glycated hemoglobin (HbA1C).
Methods
We prospectively enrolled 183 pts with HFpEF (78 ± 9 years, 38% men), including 70 (38%) diabetics (type 2 diabetes only). They underwent 2D echocardiography (n = 183), cardiac magnetic resonance (CMR) (n = 150), and were followed for a combined outcome of all-cause mortality and first HF hospitalization. The prognostic impact of diabetes and glycemic control were determined with Cox proportional hazard models, and illustrated by adjusted Kaplan Meier curves.
Results
Diabetic HFpEF pts were younger (76 ± 9 vs 80 ± 8 years, p = 0.002), more obese (BMI 31 ± 6 vs 27 ± 6 kg/m2, p = 0.001) and suffered more frequently from sleep apnea (18% vs 7%, p = 0.032). Atrial fibrillation, however, was more frequent in non-diabetic pts (69% vs 53%, p = 0.028). Although no echocardiographic difference could be detected, CMR analysis revealed a trend towards higher LV mass (66 ± 18 vs 71 ± 14 g/m2, p = 0.07) and higher levels of fibrosis (53% vs 36% of patients had ECV by T1 mapping > 33%, p = 0.05) in diabetic patients. Over 25 ± 12 months, 111 HFpEF pts (63%) reached the combined outcome (24 deaths and 87 HF hospitalizations). Diabetes was a significant predictor of mortality and hospitalization for heart failure (HR: 1.72 [1.1-2.6], p = 0.011, adjusted for age, BMI, NYHA class and renal function). In diabetic patients, lower levels of glycated hemoglobin (HbA1C < 7%) were associated with worse prognosis (HR: 2.07 [1.1-4.0], p = 0.028 adjusted for age, BMI, hemoglobin and NT-proBNP levels).
Conclusion
Our study highlights phenotypic features characterizing diabetic patients with HFpEF. Notably, they are younger and more obese than their non-diabetic counterpart, but suffer less from atrial fibrillation. Although diabetes is a predictor of poor outcome in HFpEF, intensive glycemic control (HbA1C < 7%) in diabetic patients is associated with worse prognosis.



Cardiovasc Diabetol: 18 Feb 2021; 20:48
Lejeune S, Roy C, Slimani A, Pasquet A, ... Beauloye C, Pouleur AC
Cardiovasc Diabetol: 18 Feb 2021; 20:48 | PMID: 33608002
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Impact:
Abstract

Plasma fibrin clot properties and cardiovascular mortality in patients with type 2 diabetes: a long-term follow-up study.

Bryk AH, Konieczyńska M, Polak M, Plicner D, Bochenek M, Undas A
Background
Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM.
Methods
We studied 133 T2DM patients aged 43-83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded.
Results
Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99-14.79), or decreased D-Drate (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07-8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07-15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02-18.96; HR 8.98, 95% CI 2.99-26.96; and HR 5.35, 95% CI 1.62-17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l.
Conclusions
This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.



Cardiovasc Diabetol: 17 Feb 2021; 20:47
Bryk AH, Konieczyńska M, Polak M, Plicner D, Bochenek M, Undas A
Cardiovasc Diabetol: 17 Feb 2021; 20:47 | PMID: 33602240
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Impact:
Abstract

Triglyceride-glucose index and the risk of stroke and its subtypes in the general population: an 11-year follow-up.

Wang A, Wang G, Liu Q, Zuo Y, ... Wang Y, Wang Y
Background
Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort.
Methods
A total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006-2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression.
Results
During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12-1.33, and adjusted HR 1.32, 95% CI 1.21-1.44, respectively, P for trend < 0.001). We also found a linear association between baseline TyG index with stroke. Similar results were found for ischemic stroke. However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage. Parallel results were observed for the associations of updated cumulative average TyG index with outcomes.
Conclusions
Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.



Cardiovasc Diabetol: 17 Feb 2021; 20:46
Wang A, Wang G, Liu Q, Zuo Y, ... Wang Y, Wang Y
Cardiovasc Diabetol: 17 Feb 2021; 20:46 | PMID: 33602208
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Impact:
Abstract

Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes.

Nandula SR, Kundu N, Awal HB, Brichacek B, ... Amdur RL, Sen S
Background
Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Effect of sodium glucose channel inhibitors (SGLT2i) such as Canagliflozin (CG) on a cellular biomarker such as CD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored.
Methods
This is a pilot study where 29 subjects taking metformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CG as the intervention group compared to matched placebo. Type 2 diabetes subjects (30-70 years old), with hemoglobin A1c (HbA1c) of 7-10%, were enrolled. CD34+ve cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant.
Results
A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm\'s tumor and nephrin) showed reduction with CG
Conclusion:
Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.



Cardiovasc Diabetol: 12 Feb 2021; 20:44
Nandula SR, Kundu N, Awal HB, Brichacek B, ... Amdur RL, Sen S
Cardiovasc Diabetol: 12 Feb 2021; 20:44 | PMID: 33581737
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Impact:
Abstract

The predictive utility of circulating PCSK9 levels on diabetes mellitus.

Peng J, Zhu CG, Li JJ
Increasing data including ours have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9), a novel regulator of cholesterol metabolism, may also play an important role in the development of type 2 diabetes mellitus (T2DM) and is associated with clinical outcomes in diabetic patients. Previous studies revealed that elevated plasma PCSK9 levels had a higher incidence of new-onset T2DM. Moreover, the results of available epidemiological, preclinical, and clinical studies have indicated that plasma PCSK9 concentration is correlated with glycemic parameters and can predict the adverse cardiovascular events in diabetic patients with coronary artery disease. However, there is currently no general agreement about the association of PCSK9 with T2DM. The usefulness of the circulating PCSK9 concentration as a predictor for the risk of new-onset T2DM should be clinically prudential.



Cardiovasc Diabetol: 12 Feb 2021; 20:45
Peng J, Zhu CG, Li JJ
Cardiovasc Diabetol: 12 Feb 2021; 20:45 | PMID: 33581713
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Impact:
Abstract

Cardiovascular surrogate markers and cardiometabolic therapeutics: a viewpoint learned from clinical trials on dipeptidyl peptidase-4 inhibitors.

Tanaka A, Node K
Clinical trials are often performed to investigate the effects of various types of cardiometabolic therapies on cardiovascular surrogate markers, including vascular function and biomarkers. This study platform has the potential to provide information on the suspected actions of drugs and mechanistic insights into their prognostic impact. However, despite using the same class of drugs and similar study designs we are often faced with inconsistent and even conflicting results, possibly leading to some confusion in the clinical setting. When interpreting these results, it is important to investigate what caused the differences and carefully assess the information, taking into account the research situation and the patient population investigated. Using this approach, assessment of the impact on cardiovascular surrogate markers observed in clinical studies from multiple perspectives should help to better understand the potential cardiovascular effects. In this commentary we discuss how we should interpret the effects of cardiometabolic therapeutics on vascular surrogate markers, based on viewpoints learned from the results of clinical trials on dipeptidyl peptidase-4 inhibitors. This learning strategy could also be helpful for appropriate selection of drugs for evidence-based, patient-centric, tailored medication.



Cardiovasc Diabetol: 10 Feb 2021; 20:41
Tanaka A, Node K
Cardiovasc Diabetol: 10 Feb 2021; 20:41 | PMID: 33573675
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Impact:
Abstract

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system.

Bonora BM, Raschi E, Avogaro A, Fadini GP
Background
Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS).
Methods
We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier\'s gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR).
Results
There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49-0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database.
Conclusions
In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.



Cardiovasc Diabetol: 10 Feb 2021; 20:39
Bonora BM, Raschi E, Avogaro A, Fadini GP
Cardiovasc Diabetol: 10 Feb 2021; 20:39 | PMID: 33573667
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Impact:
Abstract

Prognostic significance of diabetes mellitus in patients with atrial fibrillation.

Papazoglou AS, Kartas A, Samaras A, Vouloagkas I, ... Tzikas A, Giannakoulas G
Background
There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF).
Methods
This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM.
Results
In total 1109 AF patients were included, of whom 373 (33.6%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR = 1.40 95% confidence intervals [CI] 1.11-1.75), CV mortality (aHR = 1.39, 95% CI 1.07-1.81), sudden cardiac death (aHR = 1.73, 95% CI 1.19-2.52), stroke (aHR = 1.87, 95% CI 1.01-3.45) and the composite outcome of hospitalization or CV death (aHR = 1.27, 95% CI 1.06-1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6-8.2% being independent predictors of increased all-cause mortality, and values < 6.2% predicting significantly decreased all-cause and CV mortality.
Conclusions
The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.



Cardiovasc Diabetol: 10 Feb 2021; 20:40
Papazoglou AS, Kartas A, Samaras A, Vouloagkas I, ... Tzikas A, Giannakoulas G
Cardiovasc Diabetol: 10 Feb 2021; 20:40 | PMID: 33573666
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Impact:
Abstract

Gender differences in screening for glucose perturbations, cardiovascular risk factor management and prognosis in patients with dysglycaemia and coronary artery disease: results from the ESC-EORP EUROASPIRE surveys.

Ferrannini G, De Bacquer D, Vynckier P, De Backer G, ... Rydén L, EUROASPIRE IV & V Investigators
Background
Gender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients.
Methods
The study population (n = 16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012-2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016-2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age.
Results
Known diabetes was more common among women (32.9%) than men (28.4%, p < 0.0001). OGTT (n = 8655) disclosed IGT in 17.2% of women vs. 15.1% of men (p = 0.004) and diabetes in 13.4% of women vs. 14.6% of men (p = 0.078). In both known diabetes and newly detected dysglycaemia groups, women were older, with higher proportions of hypertension, dyslipidaemia and obesity. HbA1c was higher in women with known diabetes. Recommended targets of physical activity, blood pressure and cholesterol were achieved by significantly lower proportions of women than men. Women with known diabetes had higher risk for the endpoint than men (age-adjusted HR 1.22; 95% CI 1.04-1.43).
Conclusions
Guideline-recommended risk factor control is poorer in dysglycemic women than men. This may contribute to the worse prognosis in CAD women with known diabetes.



Cardiovasc Diabetol: 10 Feb 2021; 20:38
Ferrannini G, De Bacquer D, Vynckier P, De Backer G, ... Rydén L, EUROASPIRE IV & V Investigators
Cardiovasc Diabetol: 10 Feb 2021; 20:38 | PMID: 33573665
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Abstract

Predictive effect of triglyceride‑glucose index on clinical events in patients with type 2 diabetes mellitus and acute myocardial infarction: results from an observational cohort study in China.

Zhang Y, Ding X, Hua B, Liu Q, ... Li W, Li H
Background
Triglyceride glucose (TyG) index is considered a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular (CV) outcomes. However, the prognostic value of TyG index in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) remains unclear.
Methods
A total of 1932 consecutive patients with T2DM and AMI were enrolled in this study. Patients were divided into tertiles according to their TyG index levels. The incidence of major adverse cardiac and cerebral events (MACCEs) was recorded. The TyG index was calculated as the ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2].
Results
Competing risk regression revealed that the TyG index was positively associated with CV death [2.71(1.92 to 3.83), p < 0.001], non-fatal MI [2.02(1.32 to 3.11), p = 0.001], cardiac rehospitalization [2.42(1.81 to 3.24), p < 0.001], revascularization [2.41(1.63 to 3.55), p < 0.001] and composite MACCEs [2.32(1.92 to 2.80), p < 0.001]. The area under ROC curve of the TyG index for predicting the occurrence of MACCEs was 0.604 [(0.578 to 0.630), p < 0.001], with the cut-off value of 9.30. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for MACCEs [net reclassification improvement (NRI): 0.190 (0.094 to 0.337); integrated discrimination improvement (IDI): 0.027 (0.013 to 0.041); C-index: 0.685 (0.663 to 0.707), all p < 0.001].
Conclusions
The TyG index was significantly associated with MACCEs, suggesting that the TyG index may be a valid marker for risk stratification and prognosis in patients with T2DM and AMI. Trial registration Retrospectively registered.



Cardiovasc Diabetol: 10 Feb 2021; 20:43
Zhang Y, Ding X, Hua B, Liu Q, ... Li W, Li H
Cardiovasc Diabetol: 10 Feb 2021; 20:43 | PMID: 33573649
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Abstract

Treatment strategies in patients with diabetes and three-vessel coronary disease: What should we choose?

Liang B, Gu N
The recent study demonstrating that percutaneous coronary intervention and coronary artery bypass grafting were associated with a lower risk of death and major adverse cardiac and cerebrovascular events (composite of all-cause death, myocardial infarction, or stroke) than with medical therapy among patients with diabetes and triple-vessel disease was very interesting. However, the nature of single-center nonrandomized and nonblinded studies that are not placebo controlled limits the extrapolation and generalizability of the results. As a result, the existing body of evidence does not fully support the use of revascularization treatment strategies in patients with diabetes and triple-vessel disease. Importantly, the safety of revascularization treatment strategies in this particular population remains uncertain. Therefore, further studies are needed to assess the risks and benefits of comprehensive treatment in these patients.



Cardiovasc Diabetol: 10 Feb 2021; 20:42
Liang B, Gu N
Cardiovasc Diabetol: 10 Feb 2021; 20:42 | PMID: 33573627
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Abstract

Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study.

Cosson E, Nguyen MT, Rezgani I, Tatulashvili S, ... Brillet PY, Bihan H
Background
Epicardial adipose tissue (EAT) has anatomic and functional proximity to the heart and is considered a novel diagnostic marker and therapeutic target in cardiometabolic diseases. The aim of this study was to evaluate whether EAT volume was associated with coronary artery calcification (CAC) in people living with diabetes, independently of confounding factors.
Methods
We included all consecutive patients with diabetes whose EAT volume and CAC score were measured using computed tomography between January 1, 2019 and September 30, 2020 in the Department of Diabetology-Endocrinology-Nutrition at Avicenne Hospital, France. Determinants of EAT volume and a CAC score ≥ 100 Agatston units (AU) were evaluated.
Results
The study population comprised 409 patients (218 men). Mean (± standard deviation) age was 57 ± 12 years, and 318, 56 and 35 had type 2 (T2D), type 1 (T1D), or another type of diabetes, respectively. Mean body mass index (BMI) was 29 ± 6 kg/m2, mean AET volume 93 ± 38 cm3. EAT volume was positively correlated with age, BMI, pack-year smoking history and triglyceridaemia, but negatively correlated with HDL-cholesterol level. Furthermore, it was lower in people with retinopathy, but higher in men, in Caucasian people, in patients on antihypertensive and lipid-lowering medication, in people with nephropathy, and finally in individuals with a CAC ≥ 100 AU (CAC < 100 vs CAC ≥ 100: 89 ± 35 vs 109 ± 41 cm3, respectively, p < 0.05). In addition to EAT volume, other determinants of CAC ≥ 100 AU (n = 89, 22%) were age, T2D, ethnicity, antihypertensive and lipid-lowering medication, cumulative tobacco consumption, retinopathy, macular edema and macrovascular disease. Multivariable analysis considering all these determinants as well as gender and BMI showed that EAT volume was independently associated with CAC ≥ 100 AU (per 10 cm3 increase: OR 1.11 [1.02-1.20]).
Conclusions
EAT volume was independently associated with CAC. As it may play a role in coronary atherosclerosis in patients with diabetes, reducing EAT volume through physical exercise, improved diet and pharmaceutical interventions may improve future cardiovascular risk outcomes in this population.



Cardiovasc Diabetol: 04 Feb 2021; 20:35
Cosson E, Nguyen MT, Rezgani I, Tatulashvili S, ... Brillet PY, Bihan H
Cardiovasc Diabetol: 04 Feb 2021; 20:35 | PMID: 33546697
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Abstract

The residual cardiorenal risk in type 2 diabetes.

Giugliano D, Maiorino MI, Bellastella G, Esposito K
In this commentary, we introduce the concepts of removed and residual risks in conditioning thecardiorenal outlook of patients with type 2 diabetes (T2D). The removed cardiorenal risk represents the risk of progression of CV events (major adverse cardiovascular events, MACE; heart failure, HF) and diabetes kidney disease (DKD) taken away by optimal glycemic control or the use of newer antihyperglycemic drugs (glucagon-like peptide-1 receptor agonists, GLP-1RA, andsodium-glucose transporter-2 inhibitors, SGLT-2i) in patients with T2D, as demonstrated by the results of intensive glucose lowering trials (IGT) and cardiovascular outcome trials (CVOT). IGT have shown that successful glycemic control has modest benefits, as the removed cardiorenal risk ranges from 9% for MACE, to 20% for progression of DKD and to 0% for HF. The removed risk of MACE is 13% for GLP-1RA and 12% for SGLT-2i. However, SGLT-2i, as compared with GLP-1RA, removed twofold more risk (39% vs 17%) for kidney outcomes and fourfold more risk (33% vs 9%) for HF. Dipeptidyl peptidase-4 inhibitors have no clinically important cardiorenal benefits, as residual risk is 99% for MACE, 100% for kidney outcomes (excluding new albuminuria), and 100% for HF. Although the results of some real world, population-based cohort studies suggest the possibility that the cardiorenal protection afforded by newer antihyperglycemic drugs is additive to that of optimal glycemic control, only specific randomized controlled trials could answer this question.



Cardiovasc Diabetol: 04 Feb 2021; 20:36
Giugliano D, Maiorino MI, Bellastella G, Esposito K
Cardiovasc Diabetol: 04 Feb 2021; 20:36 | PMID: 33546683
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This program is still in alpha version.