Journal: Cardiovasc Diabetol

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Abstract

Epicardial adipose tissue and severe Coronavirus Disease 19.

Bihan H, Heidar R, Beloeuvre A, Allard L, ... Brillet PY, Cosson E
Background
Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with Coronavirus Disease 19 (COVID-19) severity. We aimed to investigate whether an association also exists for EAT.
Material and methods
We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 [Formula: see text] 6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity.
Results
We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters.
Conclusions
Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.

© 2021. The Author(s).

Cardiovasc Diabetol: 19 Jul 2021; 20:147
Bihan H, Heidar R, Beloeuvre A, Allard L, ... Brillet PY, Cosson E
Cardiovasc Diabetol: 19 Jul 2021; 20:147 | PMID: 34284784
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Abstract

Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease.

Sasso FC, Pafundi PC, Simeon V, De Nicola L, ... Minutolo R, NID-2 Study Group Investigators
Background
Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated.
Methods
Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death.
Results
At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4-13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30-0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29-0.93, P = 0.027).
Conclusion
MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical
Trial registration:
ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.

© 2021. The Author(s).

Cardiovasc Diabetol: 15 Jul 2021; 20:145
Sasso FC, Pafundi PC, Simeon V, De Nicola L, ... Minutolo R, NID-2 Study Group Investigators
Cardiovasc Diabetol: 15 Jul 2021; 20:145 | PMID: 34271948
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Abstract

Association between triglyceride-glucose index and risk of arterial stiffness: a cohort study.

Wu S, Xu L, Wu M, Chen S, Wang Y, Tian Y
Background
Triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, has been reported to be associated with arterial stiffness. However, previous studies were limited by the cross-sectional design. The purpose of this study was to explore the longitudinal association between TyG index and progression of arterial stiffness.
Methods
A total of 6028 participants were derived from the Kailuan study. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Arterial stiffness progression was assessed by the annual growth rate of repeatedly measured baPWV. Multivariate linear regression models were used to estimate the cross-sectional association of TyG index with baPWV, and Cox proportional hazard models were used to investigate the longitudinal association between TyG index and the risk of arterial stiffness.
Results
Multivariate linear regression analyses showed that each one unit increase in the TyG index was associated with a 39 cm/s increment (95%CI, 29-48 cm/s, P < 0.001) in baseline baPWV and a 0.29 percent/year increment (95%CI, 0.17-0.42 percent/year, P < 0.001) in the annual growth rate of baPWV. During 26,839 person-years of follow-up, there were 883 incident cases with arterial stiffness. Participants in the highest quartile of TyG index had a 58% higher risk of arterial stiffness (HR, 1.58; 95%CI, 1.25-2.01, P < 0.001), as compared with those in the lowest quartile of TyG index. Additionally, restricted cubic spline analysis showed a significant dose-response relationship between TyG index and the risk of arterial stiffness (P non-linearity = 0.005).
Conclusion
Participants with a higher TyG index were more likely to have a higher risk of arterial stiffness. Subjects with a higher TyG index should be aware of the following risk of arterial stiffness progression, so as to establish lifestyle changes at an early stage.

© 2021. The Author(s).

Cardiovasc Diabetol: 15 Jul 2021; 20:146
Wu S, Xu L, Wu M, Chen S, Wang Y, Tian Y
Cardiovasc Diabetol: 15 Jul 2021; 20:146 | PMID: 34271940
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Abstract

Prognostic value of fibrinogen in patients with coronary artery disease and prediabetes or diabetes following percutaneous coronary intervention: 5-year findings from a large cohort study.

Yuan D, Jiang P, Zhu P, Jia S, ... Gao Z, Yuan J
Background
Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM).
Methods
6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality.
Results
FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12).
Conclusions
FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

© 2021. The Author(s).

Cardiovasc Diabetol: 15 Jul 2021; 20:143
Yuan D, Jiang P, Zhu P, Jia S, ... Gao Z, Yuan J
Cardiovasc Diabetol: 15 Jul 2021; 20:143 | PMID: 34271936
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Abstract

Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets\' attainment in subjects with and without type 2 diabetes.

Morieri ML, Perrone V, Veronesi C, Degli Esposti L, ... Vigili de Kreutzenberg S, Avogaro A
Background
This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients.
Methods
We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone.
Results
We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78-100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from - 3 to - 11%, p < 0.001, HIS + ezetimibe vs. HIS-from - 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a \"treat to absolute LDL-cholesterol levels\" approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention.
Conclusions
Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.

© 2021. The Author(s).

Cardiovasc Diabetol: 15 Jul 2021; 20:144
Morieri ML, Perrone V, Veronesi C, Degli Esposti L, ... Vigili de Kreutzenberg S, Avogaro A
Cardiovasc Diabetol: 15 Jul 2021; 20:144 | PMID: 34271920
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Abstract

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

Tuttolomondo A, Del Cuore A, La Malfa A, Casuccio A, ... Guercio G, Pinto A
Background
Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age.
Aims
The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices.
Methods
We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection.
Results
63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance.
Discussion
Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

© 2021. The Author(s).

Cardiovasc Diabetol: 13 Jul 2021; 20:142
Tuttolomondo A, Del Cuore A, La Malfa A, Casuccio A, ... Guercio G, Pinto A
Cardiovasc Diabetol: 13 Jul 2021; 20:142 | PMID: 34261479
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Abstract

Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14 years of follow-up in the Tehran Lipid and Glucose Study.

Moazzeni SS, Hizomi Arani R, Deravi N, Hasheminia M, ... Azizi F, Hadaegh F
Background
To examine the impact of weight change on incident cardiovascular disease and coronary heart disease (CVD/CHD) among an Iranian population with type 2 diabetes mellitus (T2DM).
Methods
The study population included 763 participants with T2DM aged ≥ 30 years without a history of CVD and cancer at baseline. Two weight measurements done at baseline and about 3 years later. Based on their weight change, they categorized into: > 5% loss, 3-5% loss, stable (± < 3%), 3-5% gain, > 5% gain. Participants were then followed for incident CVD/CHD annually up to 20 March 2018. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, educational level, current smoking, glucose-lowering drug use, family history of CVD, hypertension, hypercholesterolemia, chronic kidney disease, and fasting plasma glucose (FPG) were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for incident CVD/CHD, considering stable weight as reference.
Results
After the weight change measurement, during a median follow-up of 14.4 years, 258 CVD and 214 CHD occurred. Over 5% weight gain was associated with reduced risks of CVD and CHD development by the HRs of 0.70 [95% CI 0.48-1.01; P-value: 0.058] and 0.61 [0.40-0.93], respectively, in multivariable analysis. After further adjustment for FPG change, the HRs of weight gain > 5% were attenuated to 0.75 [0.51-1.10; P-value: 0.138] and 0.66 [043-1.01; P-value: 0.053] for incident CVD and CHD, respectively. The effect of weight loss > 5% was in opposite direction among those older versus younger than 60 years; with suggestive increased risk (not statistically significant) of incident CHD/CVD for the older group. Moreover, weight gain > 5% significantly reduced the risk of CHD only among those older than 60 years (P-value for interaction < 0.2). Furthermore, weight gain > 5% had an association with lower risk of CVD and CHD among sulfonylurea users (0.56 [0.32-0.98] for CVD and 0.54 [0.29-0.99] for CHD).
Conclusions
Our results with a long-term follow-up showed that weight gain > 5% was associated with better CVD/CHD outcomes among Iranian participants with T2DM, especially older ones. Moreover, we did not find an unfavorable impact on incident CVD/CHD for sulfonylurea-induced weight gain.

© 2021. The Author(s).

Cardiovasc Diabetol: 11 Jul 2021; 20:141
Moazzeni SS, Hizomi Arani R, Deravi N, Hasheminia M, ... Azizi F, Hadaegh F
Cardiovasc Diabetol: 11 Jul 2021; 20:141 | PMID: 34253199
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Abstract

Sex-related disparities in the incidence and outcomes of hemorrhagic stroke among type 2 diabetes patients: a propensity score matching analysis using the Spanish National Hospital Discharge Database for the period 2016-18.

Lopez-de-Andres A, Jimenez-Garcia R, Hernández-Barrera V, Jiménez-Trujillo I, ... de Miguel-Diez J, Lopez-Herranz M
Background
To analyze incidence, use of therapeutic procedures, use of oral anticoagulants (OACs) and antiplatelet agents prior to hospitalization, and in-hospital outcomes among patients who were hospitalized with hemorrhagic stroke (HS) according to the presence of type 2 diabetes mellitus (T2DM) in Spain (2016-2018) and to assess the role of sex differences among those with T2DM.
Methods
Using the Spanish National Hospital Discharge Database we estimated the incidence of HS hospitalizations in men and women aged ≥ 35 years with and without T2DM. Propensity score matching (PSM) was used to compare population subgroups according to sex and the presence of T2DM.
Results
HS was coded in 31,425 men and 24,975 women, of whom 11,915 (21.12%) had T2DM. The adjusted incidence of HS was significantly higher in patients with T2DM (both sexes) than in non-T2DM individuals (IRR 1.15; 95% CI 1.12-1.17). The incidence of HS was higher in men with T2DM than in T2DM women (adjusted IRR 1.60; 95% CI 1.57-1.63). After PSM, men and women with T2DM have significantly less frequently received decompressive craniectomy than those without T2DM. In-hospital mortality (IHM) was higher among T2DM women than matched non-T2DM women (32.89% vs 30.83%; p = 0.037), with no differences among men. Decompressive craniectomy was significantly more common in men than in matched women with T2DM (5.81% vs. 3.33%; p < 0.001). IHM was higher among T2DM women than T2DM men (32.89% vs. 28.28%; p < 0.001). After adjusting for confounders with multivariable logistic regression, women with T2DM had a 18% higher mortality risk than T2DM men (OR 1.18; 95% CI 1.07-1.29). Use of OACs and antiplatelet agents prior to hospitalization were associated to higher IHM in men and women with and without T2DM.
Conclusions
T2DM is associated with a higher incidence of HS and with less frequent use of decompressive craniectomy in both sexes, but with higher IHM only among women. Sex differences were detected in T2DM patients who had experienced HS, with higher incidence rates, more frequent decompressive craniectomy, and lower IHM in men than in women.

© 2021. The Author(s).

Cardiovasc Diabetol: 08 Jul 2021; 20:138
Lopez-de-Andres A, Jimenez-Garcia R, Hernández-Barrera V, Jiménez-Trujillo I, ... de Miguel-Diez J, Lopez-Herranz M
Cardiovasc Diabetol: 08 Jul 2021; 20:138 | PMID: 34243780
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Abstract

Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia.

Real J, Vlacho B, Ortega E, Vallés JA, ... Mauricio D, Franch-Nadal J
Background
Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain.
Methods
CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke).
Results
After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47-0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31-0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47-0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52-0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54-0.80; p < 0.001).
Conclusions
In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

© 2021. The Author(s).

Cardiovasc Diabetol: 08 Jul 2021; 20:139
Real J, Vlacho B, Ortega E, Vallés JA, ... Mauricio D, Franch-Nadal J
Cardiovasc Diabetol: 08 Jul 2021; 20:139 | PMID: 34243779
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Abstract

Triglyceride-glucose index is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents.

Zhu Y, Liu K, Chen M, Liu Y, ... Zhang J, Zhao Y
Background
The triglyceride-glucose (TyG) index is an alternative marker of insulin resistance (IR) and is closely associated with the prevalence and prognosis of atherosclerotic cardiovascular disease (ASCVD). However, the association between the TyG index and in-stent restenosis (ISR) after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) remains unknown.
Methods
The present study retrospectively recruited patients who were admitted for ACS and underwent coronary angiography at 6 to 24 months after successful DES-based percutaneous coronary intervention (PCI). In addition, we calculated the TyG index with the following formula: Ln(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2) and divided patients into 3 groups according to the tertile of the TyG index. Most importantly, multivariate logistic regression analysis models were also constructed to assess the association between the TyG index and DES-ISR in patients with ACS.
Results
A total of 1574 patients with ACS (58.4 ± 9.4 years, 77.4% male) were included in this study. At the median follow-up time of 12 (9-14) months, the prevalence of DES-ISR increased stepwise with the increasing tertile of the TyG index (11.6% vs 17.3% vs 19.4%, p = 0.002), and the TyG index was also higher in the ISR group than in the non-ISR group (9.00 ± 0.58 vs 8.84 ± 0.61, p < 0.001). In addition, the positive association between the TyG index and the prevalence of DES-ISR was also determined in the fully adjusted model (TyG, per 1-unit increase: OR 1.424, 95% CI 1.116 to 1.818, p = 0.005; tertile of TyG, the OR (95% CI) values for tertile 2 and tertile 3 were 1.454 (1.013 to 2.087) and 1.634 (1.125 to 2.374), respectively, with tertile 1 as a reference). The association was also reflected in most subgroups. Moreover, adding the TyG index to the predictive model for DES-ISR in patients with ACS could contribute to an increase in C-statistics (0.675 vs 0.659, p = 0.010), categorical net reclassification improvement (0.090, p < 0.001), and integrated discrimination improvement (0.004, p = 0.040).
Conclusion
An elevated TyG index was independently and positively associated with DES-ISR in patients with ACS who underwent PCI. However, the incremental predictive value of the TyG index for DES-ISR was slight. To further confirm our findings, future studies are needed.



Cardiovasc Diabetol: 07 Jul 2021; 20:137
Zhu Y, Liu K, Chen M, Liu Y, ... Zhang J, Zhao Y
Cardiovasc Diabetol: 07 Jul 2021; 20:137 | PMID: 34238294
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Abstract

A cross sectional study to compare cardiac structure and diastolic function in adolescents and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

Shah AS, Isom S, Dabelea D, D\'Agostino R, ... Urbina EM, SEARCH for Diabetes in Youth Study Group
Aims
To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function.
Methods
In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function.
Results
Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p < 0.05). Abnormal diastolic function, quantified using healthy controls, was pronounced in both groups but greater in those with T2D than T1D (T2D: 57.7% vs T1D: 47.2%, respectively), p < 0.05. Risk factors associated with worse diastolic function included older age at diabetes diagnosis, female sex, higher BP, heart rate and HbA1c and longer diabetes duration.
Conclusions
LV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls.



Cardiovasc Diabetol: 06 Jul 2021; 20:136
Shah AS, Isom S, Dabelea D, D'Agostino R, ... Urbina EM, SEARCH for Diabetes in Youth Study Group
Cardiovasc Diabetol: 06 Jul 2021; 20:136 | PMID: 34233679
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Abstract

Association of TyG index and TG/HDL-C ratio with arterial stiffness progression in a non-normotensive population.

Wu Z, Zhou D, Liu Y, Li Z, ... Guo X, Tao L
Background
Cross-sectional studies have reported that insulin resistance (IR) is associated with arterial stiffness. However, the relationship between IR and arterial stiffness progression remains unclear. This study aims to evaluate the association of triglyceride glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio with arterial stiffness progression in a non-normotensive population.
Methods
A total of 1895 prehypertensive (systolic pressure 120-139 mmHg or diastolic pressure 80-90 mmHg) or hypertensive (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg or using antihypertensive medication) participants were enrolled in 2013 and 2014, and followed until December 31, 2019. Arterial stiffness progression was measured by brachial-ankle pulse wave velocity (baPWV) change (absolute difference between baseline and last follow-up), baPWV change rate (change divided by following years), and baPWV slope (regression slope between examination year and baPWV).
Results
During a median follow-up of 4.71 years, we observed an increasing trend of baPWV in the population. There were linear and positive associations of the TyG index and TG/HDL-C ratio with the three baPWV parameters. The difference (95% CI) in baPWV change (cm/s) comparing participants in the highest quartile versus the lowest of TyG index and TG/HDL-C ratio were 129.5 (58.7-200.0) and 133.4 (52.0-214.9), respectively. Similarly, the evaluated baPWV change rates (cm/s/year) were 37.6 (15.3-60.0) and 43.5 (17.8-69.2), while the slopes of baPWV were 30.6 (9.3-51.8) and 33.5 (9.0-58.0). The observed association was stronger in the hypertensive population.
Conclusion
Our study indicates that the TyG index and TG/HDL-C ratio are significantly associated with arterial stiffness progression in hypertensive population, not in prehypertensive population.



Cardiovasc Diabetol: 05 Jul 2021; 20:134
Wu Z, Zhou D, Liu Y, Li Z, ... Guo X, Tao L
Cardiovasc Diabetol: 05 Jul 2021; 20:134 | PMID: 34229681
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Impact:
Abstract

Up and down waves of glycemic control and lower-extremity amputation in diabetes.

Caruso P, Scappaticcio L, Maiorino MI, Esposito K, Giugliano D
Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in \"the perfect wave\" of NHANES, including the years 2007-2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.



Cardiovasc Diabetol: 05 Jul 2021; 20:135
Caruso P, Scappaticcio L, Maiorino MI, Esposito K, Giugliano D
Cardiovasc Diabetol: 05 Jul 2021; 20:135 | PMID: 34229673
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Impact:
Abstract

Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

Cardoso CRL, Leite NC, Salles GF
Background
The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes.
Methods
In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index.
Results
During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination.
Conclusions
Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.



Cardiovasc Diabetol: 05 Jul 2021; 20:133
Cardoso CRL, Leite NC, Salles GF
Cardiovasc Diabetol: 05 Jul 2021; 20:133 | PMID: 34229668
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Impact:
Abstract

The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats.

Daud E, Ertracht O, Bandel N, Moady G, ... Reuveni T, Atar S
Background
Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction.
Methods
Fourteen non-diabetic rats underwent myocardial infarction induction, and treated or not (control)immediately after myocardial infarction by daily empagliflozin (30 mg/kg/day). We evaluated cardiac function at baseline, 2 and 4 weeks after myocardial infarction by echocardiography, and prior to sacrifice by Millar pressure-volume system. We performed histological and biochemical evaluation of fibrosis and humoral factors promoting fibrosis.
Results
Baseline ejection fractions were 69.9 ± 5.3% and 76.4 ± 5.4%, and dropped to final values of 40.1 ± 5.8% and 39.4 ± 5.4% in the control and empagliflozin groups, respectively (P < 0.001 vs. baseline, P > 0.05 between groups). Collagen deposition, measured as collagen volume fraction, was higher in both the scar and the remote cardiac areas of the control group 79.1 ± 6.2% and 4.6 ± 2.5% for control, and 53.8 ± 5.4% and 2.5 ± 1.3% for empagliflozin group, respectively (P < 0.05 for each). Remote cardiac muscle collagen, measured by hydroxyproline, was 4.1 ± 0.4 μg/μl and 3.6 ± 0.2 μg/μl (P = 0.07). TGF-β1 and Smad3 expression decreased by empagliflozin-18.73 ± 16.32%, 9.16 ± 5.69% and 16.32 ± 5.4%, 7.00 ± 5.28% in the control and empagliflozin groups, respectively (P < 0.05).
Conclusion/interpretation
Empagliflozin administered early after myocardial infarction reduce myocardial fibrosis and inhibit the TGF-β1/Smad3 fibrotic pathway, probably prior to exerting any hemodynamic or physiological effect.



Cardiovasc Diabetol: 01 Jul 2021; 20:132
Daud E, Ertracht O, Bandel N, Moady G, ... Reuveni T, Atar S
Cardiovasc Diabetol: 01 Jul 2021; 20:132 | PMID: 34215277
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Impact:
Abstract

Prescribing sodium-glucose co-transporter-2 inhibitors for type 2 diabetes in primary care: influence of renal function and heart failure diagnosis.

Hinton W, Feher MD, Munro N, Joy M, de Lusignan S
Background
Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are licenced for initiation for glucose lowering in people with type 2 diabetes (T2DM) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2). However, recent trial data have shown that these medications have renal and cardio-protective effects, even for impaired kidney function. The extent to which trial evidence and updated guidelines have influenced real-world prescribing of SGLT-2is is not known, particularly with co-administration of diuretics.
Methods
We performed a cross-sectional analysis of people with T2DM registered with practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database on the 31st July 2019. We calculated the percentage of people prescribed SGLT-2is according to eGFR categories (< 45, 45-59, and ≥ 60 mL/min/1.73m2), with a heart failure diagnosis and stratified by body mass index categories (underweight, normal weight, overweight, obese), and with concomitant prescription of a diuretic. Multilevel logistic regression analysis was performed to determine whether heart failure diagnosis and renal function were associated with SGLT-2i prescribing.
Results
From a population of 242,624 people with T2DM across 419 practices, 11.0% (n = 26,700) had been prescribed SGLT-2is. The majority of people initiated SGLT-2is had an eGFR ≥ 60 mL/min/1.73m2 (93.2%), and 4.3% had a heart failure diagnosis. 9,226 (3.8%) people were prescribed SGLT-2is as an add-on to their diuretic prescription. People in the highest eGFR category (≥ 60 mL/min/1.73m2) were more likely to be prescribed SGLT-2is than those in eGFR lower categories. Overweight (OR 2.05, 95% CI 1.841-2.274) and obese people (OR 3.84, 95% CI 3.472-4.250) were also more likely to be prescribed these medications, whilst use of diuretics (OR 0.74, 95% CI 0.682-0.804) and heart failure (OR 0.81, 95% CI 0.653-0.998) were associated with lower odds of being prescribed SGLT-2is.
Conclusions
Prescribing patterns of SGLT-2is for glucose lowering in T2DM in primary care generally concur with licenced indications according to recommended renal thresholds. A small percentage of people with heart failure were prescribed SGLT-2is for T2DM. An updated analysis is merited should UK National Institute for Health Care and Excellence prescribing guidelines for T2DM be revised to incorporate new data on the benefits for those with reduced renal function or with heart failure.



Cardiovasc Diabetol: 27 Jun 2021; 20:130
Hinton W, Feher MD, Munro N, Joy M, de Lusignan S
Cardiovasc Diabetol: 27 Jun 2021; 20:130 | PMID: 34183018
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Impact:
Abstract

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial.

Tanaka A, Shimabukuro M, Teragawa H, Okada Y, ... Node K, EMBLEM Investigators
Backgrounds/aim
Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD).
Methods
The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration.
Results
In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by - 2.23% (95% CI - 5.72 to 1.25) at week 4, - 8.07% (- 12.76 to - 3.37) at week 12, and - 5.60% (- 9.87 to - 1.32) at week 24; eEV by - 70.3 mL (95% CI - 136.8 to - 3.8) at week 4, - 135.9 mL (- 209.6 to - 62.3) at week 12, and - 144.4 mL (- 226.3 to - 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV.
Conclusions
Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.



Cardiovasc Diabetol: 27 Jun 2021; 20:105
Tanaka A, Shimabukuro M, Teragawa H, Okada Y, ... Node K, EMBLEM Investigators
Cardiovasc Diabetol: 27 Jun 2021; 20:105 | PMID: 34183012
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Impact:
Abstract

Triglyceride glucose index combined with plaque characteristics as a novel biomarker for cardiovascular outcomes after percutaneous coronary intervention in ST-elevated myocardial infarction patients: an intravascular optical coherence tomography study.

Zhao X, Wang Y, Chen R, Li J, ... Zhao H, Yan H
Background:
and aim
This prospective study explored plaque morphology according to the underlying culprit lesion pathology (rupture versus erosion) in relation to the triglyceride glucose (TyG) index in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for culprit lesions to elucidate the effects of the TyG index and type of plaque on the incidence of major adverse cardiovascular events (MACEs).
Methods and outcomes
A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. The TyG index was calculated using the formula ln[fasting TG (mg/dL) × fasting glucose (mg/dL)/2]. Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the TyG tertiles. MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke. In fully adjusted analyses, the middle tertile of TyG was significantly associated with greater rates of MACEs in patients with PR but not in those with PE (relative to the low tertile, HR [hazard ratio], 6.01; 95% confidence interval [CI], 1.25-28.88; P = 0.025). Cox regression models indicated a significantly higher HR for MACEs in patients in the middle tertile of TyG than in those in the low tertile of TyG after full additional adjustment (HR, 5.45; 95% CI, 1.10-27.09; P = 0.038). However, being in the high tertile of TyG independently and significantly increased the risk of major bleeding events among patients with PE (HR, 2.50; 95% CI, 1.11-5.65; P = 0.028). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the TyG index combined with the morphological characteristics of plaque after full adjustment was 0.881 (sensitivity = 94.74%, specificity = 78.04%, cut-off level = 0.73). Kaplan-Meier curves were generated for the cumulative incidence of MACEs for up to a median of 1.98 years stratified by tertiles of TyG among the PR and PE subgroups. Among patients with PR, there were significant differences among the tertiles of TyG (p = 0.030).

Conclusion:
and relevance
Microstructural OCT features of culprit lesions in combination with the TyG index, a surrogate estimate of insulin resistance, can be used in clinical practice to support risk stratification and predict adverse events in patients with STEMI.



Cardiovasc Diabetol: 27 Jun 2021; 20:131
Zhao X, Wang Y, Chen R, Li J, ... Zhao H, Yan H
Cardiovasc Diabetol: 27 Jun 2021; 20:131 | PMID: 34183007
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Impact:
Abstract

Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals: a cross-sectional study.

Birukov A, Cuadrat R, Polemiti E, Eichelmann F, Schulze MB
Background
Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata.
Methods
We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader™, vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer™. A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers.
Results
Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and - 0.04 (- 0.05; - 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (- 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata.
Conclusions
Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata.



Cardiovasc Diabetol: 26 Jun 2021; 20:110
Birukov A, Cuadrat R, Polemiti E, Eichelmann F, Schulze MB
Cardiovasc Diabetol: 26 Jun 2021; 20:110 | PMID: 34176469
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Impact:
Abstract

Mortality rates and cardiovascular disease burden in type 2 diabetes by occupation, results from all Swedish employees in 2002-2015.

Carlsson S, Andersson T, Talbäck M, Feychting M
Objective
To identify occupations where employees with type 2 diabetes have a high risk of cardiovascular disease (CVD) and mortality, and their prevalence of CVD risk factors. This study can contribute in the creation of targeted interventions at the workplace.
Research design and methods
This nationwide registry-based study included all employees with type 2 diabetes born in Sweden in 1937-1979 (n = 180,620) and followed up in 2002-2015. We calculated age-standardized incidence (per 100,000 person-years) of all-cause and CVD mortality, ischemic heart disease (IHD) and stroke across the 30 most common occupations. Information on prognostic factors was retrieved from the National Diabetes Register.
Results
In males with type 2 diabetes, mortality rates were highest in manufacturing workers (1782) and machine operators (1329), and lowest in specialist managers (633). The risk of death at age 61-70 years was 21.8% in manufacturing workers and 8.5% in managers. In females with type 2 diabetes, mortality rates were highest in manufacturing workers (1150) and cleaners (876), and lowest in writers and artists (458); the risk of death at age 61-70 years was 12.4% in manufacturing workers and 4.3% in writers and artists. The same occupations also had relatively high incidences of CVD mortality, IHD and stroke. Occupational groups with poor prognosis had high prevalence of CVD risk factors including poor glycemic control, smoking and obesity.
Conclusions
Manufacturing workers, machine operators and cleaners with type 2 diabetes have two to three times higher mortality rates than managers, writers and artists with type 2 diabetes. Major health gains would be made if targeted workplace interventions could reduce CVD risk factors in these occupations.



Cardiovasc Diabetol: 25 Jun 2021; 20:129
Carlsson S, Andersson T, Talbäck M, Feychting M
Cardiovasc Diabetol: 25 Jun 2021; 20:129 | PMID: 34174883
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Impact:
Abstract

Circulating ANGPTL8 levels and risk of kidney function decline: Results from the 4C Study.

Zou H, Xu Y, Meng X, Li D, ... Liu Z, Yu X
Background
ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study.
Methods
We analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting.
Results
There were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41-4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01-1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001).
Conclusions
Participants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.



Cardiovasc Diabetol: 23 Jun 2021; 20:127
Zou H, Xu Y, Meng X, Li D, ... Liu Z, Yu X
Cardiovasc Diabetol: 23 Jun 2021; 20:127 | PMID: 34167540
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Impact:
Abstract

Triglyceride-glucose index in the development of peripheral artery disease: findings from the Atherosclerosis Risk in Communities (ARIC) Study.

Gao JW, Hao QY, Gao M, Zhang K, ... Zhang SL, Liu PM
Background
It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).
Methods
We included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987-1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.
Results
Over a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049-1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028-1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132-1.740) and 1.742 (1.294-2.344), respectively] after multivariate adjustments for traditional PAD risk factors.
Conclusions
Higher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.
Trial registration
Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.



Cardiovasc Diabetol: 23 Jun 2021; 20:126
Gao JW, Hao QY, Gao M, Zhang K, ... Zhang SL, Liu PM
Cardiovasc Diabetol: 23 Jun 2021; 20:126 | PMID: 34167539
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Impact:
Abstract

Relationship between diabetes mellitus and atrial fibrillation prevalence in the Polish population: a report from the Non-invasive Monitoring for Early Detection of Atrial Fibrillation (NOMED-AF) prospective cross-sectional observational study.

Gumprecht J, Lip GYH, Sokal A, Średniawa B, ... Opolski G, Kalarus Z
Background
The global burden of atrial fibrillation (AF) and diabetes mellitus (DM) is constantly rising, leading to an increasing healthcare burden of stroke. AF often remains undiagnosed due to the occurrence in an asymptomatic, silent form, i.e., silent AF (SAF). The study aims to evaluate the relationships between DM and AF prevalence using a mobile long-term continuous ECG telemonitoring vest in a representative Polish and European population ≥ 65 years for detection of AF, symptomatic or silent.
Methods
A representative sample of 3014 participants from the cross-sectional NOMED-AF study was enrolled in the analyses (mean age 77.5, 49.1% female): 881 (29.2%) were diagnosed with DM. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1days.
Results
Overall, AF was reported in 680 (22.6%) of the whole study population. AF prevalence was higher among subjects with concomitant DM (DM+) versus those without DM (DM-) [25%, 95% CI 22.5-27.8% vs 17%; 95% CI 15.4-18.5% respectively, p < 0.001]. DM patients were commonly associated with SAF [9%; 95% CI 7.9-11.4 vs 7%; 95% CI 5.6-7.5 respectively, p < 0.001], and persistent/permanent AF [12.2%; 95% CI 10.3-14.3 vs 6.9%; 95% CI 5.9-8.1 respectively, p < 0.001] compared to subjects without DM. The prolonged screening was associated with a higher percentage of newly established AF diagnosis in DM+ vs DM- patients (5% vs 4.5% respectively, p < 0.001). In addition to shared risk factors, DM+ subjects were associated with different AF and SAF independent risk factors compared to DM- individuals, including thyroid disease, peripheral/systemic thromboembolism, hypertension, physical activity and prior percutaneous coronary intervention/coronary artery bypass graft surgery.
Conclusions
AF affects 1 out of 4 subjects with concomitant DM. The higher prevalence of AF and SAF among DM subjects than those without DM highlights the necessity of active AF screening specific AF risk factors assessment amongst the diabetic population.
Trial registration
NCT03243474.



Cardiovasc Diabetol: 23 Jun 2021; 20:128
Gumprecht J, Lip GYH, Sokal A, Średniawa B, ... Opolski G, Kalarus Z
Cardiovasc Diabetol: 23 Jun 2021; 20:128 | PMID: 34167520
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Impact:
Abstract

Mechanisms of reduced peak oxygen consumption in subjects with uncomplicated type 2 diabetes.

Nesti L, Pugliese NR, Sciuto P, De Biase N, ... Masi S, Natali A
Background
Type 2 diabetes mellitus (T2D) increases the risk of incident heart failure (HF), whose earliest fingerprint is effort intolerance (i.e. impaired peak oxygen consumption, or VO2peak). In the uncomplicated T2D population, however, the prevalence of effort intolerance and the underpinning mechanistic bases are uncertain. Leveraging the multiparametric characterization allowed by imaging-cardiopulmonary exercise testing (iCPET), the aim of this study is to quantify effort intolerance in T2D and to dissect the associated cardiopulmonary alterations.
Methods
Eighty-eight adults with well-controlled and uncomplicated T2D and no criteria for HF underwent a maximal iCPET with speckle tracking echocardiography, vascular and endothelial function assessment, as well as a comprehensive biohumoral characterization. Effort intolerance was defined by a VO2peak below 80% of maximal predicted oxygen uptake.
Results
Forty-eight patients (55%) had effort intolerance reaching a lower VO2peak than T2D controls (16.5 ± 3.2 mL/min/kg, vs 21.7 ± 5.4 mL/min/kg, p < 0.0001). Despite a comparable cardiac output, patients with effort intolerance showed reduced peak peripheral oxygen extraction (11.3 ± 3.1 vs 12.7 ± 3.3 mL/dL, p = 0.002), lower VO2/work slope (9.9 ± 1.2 vs 11.2 ± 1.4, p < 0.0001), impaired left ventricle systolic reserve (peak S\' 13.5 ± 2.8 vs 15.2 ± 3.0, p = 0.009) and global longitudinal strain (peak-rest ΔGLS 1.7 ± 1.5 vs 2.5 ± 1.8, p = 0.03) than subjects with VO2peak above 80%. Diastolic function, vascular resistance, endothelial function, biohumoral exams, right heart and pulmonary function indices did not differ between the two groups.
Conclusions
Effort intolerance and reduced VO2peak is a severe and highly prevalent condition in uncomplicated, otherwise asymptomatic T2D. It results from a major defect in skeletal muscle oxygen extraction coupled with a subtle myocardial systolic dysfunction.



Cardiovasc Diabetol: 21 Jun 2021; 20:124
Nesti L, Pugliese NR, Sciuto P, De Biase N, ... Masi S, Natali A
Cardiovasc Diabetol: 21 Jun 2021; 20:124 | PMID: 34158062
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Impact:
Abstract

Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial.

Schwartz GG, Nicholls SJ, Toth PP, Sweeney M, ... Ginsberg HN, Ray KK
Background
In stable patients with type 2 diabetes (T2D), insulin treatment is associated with elevated risk for major adverse cardiovascular events (MACE). Patients with acute coronary syndrome (ACS) and T2D are at particularly high risk for recurrent MACE despite evidence-based therapies. It is uncertain to what extent this risk is further magnified in patients with recent ACS who are treated with insulin. We examined the relationship of insulin use to risk of MACE and modification of that risk by apabetalone, a bromodomain and extra-terminal (BET) protein inhibitor.
Methods
The analysis utilized data from the BETonMACE phase 3 trial that compared apabetalone to placebo in patients with T2D, low HDL cholesterol, andACS. The primary MACE outcome (cardiovascular death, myocardial infarction, or stroke) was examined according to insulin treatment and assigned study treatment. Multivariable Cox regression was used to determine whether insulin use was independently associated with the risk of MACE.
Results
Among 2418 patients followed for median 26.5 months, 829 (34.2%) were treated with insulin. Despite high utilization of evidence-based treatments including coronary revascularization, intensive statin treatment, and dual antiplatelet therapy, the 3-year incidence of MACE in the placebo group was elevated among insulin-treated patients (20.4%) compared to those not-treated with insulin (12.8%, P = 0.0001). Insulin treatment remained strongly associated with the risk of MACE (HR 2.10, 95% CI 1.42-3.10, P = 0.0002) after adjustment for demographic, clinical, and treatment variables. Apabetalone had a consistent, favorable effect on MACE in insulin-treated and not insulin-treated patients.
Conclusion
Insulin-treated patients with T2D, low HDL cholesterol, and ACS are at high risk for recurrent MACE despite the use of evidence-based, contemporary therapies. A strong association of insulin treatment with risk of MACE persists after adjustment for other characteristics associated with MACE. There is unmet need for additional treatments to mitigate this risk. Trial registration ClinicalTrials.gov NCT02586155, registered October 26, 2015.



Cardiovasc Diabetol: 21 Jun 2021; 20:125
Schwartz GG, Nicholls SJ, Toth PP, Sweeney M, ... Ginsberg HN, Ray KK
Cardiovasc Diabetol: 21 Jun 2021; 20:125 | PMID: 34158057
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Abstract

Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes.

Groenewegen A, Zwartkruis VW, Cekic B, de Boer RA, ... Rutten FH, Hollander M
Background
Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed.
Methods
A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners\' Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated.
Results
Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06-1.30) for atrial fibrillation, 1.66 (1.55-1.83) for ischaemic heart disease, and 2.36 (2.10-2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter.
Conclusion
There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.



Cardiovasc Diabetol: 15 Jun 2021; 20:123
Groenewegen A, Zwartkruis VW, Cekic B, de Boer RA, ... Rutten FH, Hollander M
Cardiovasc Diabetol: 15 Jun 2021; 20:123 | PMID: 34134731
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Abstract

Long-term prognosis in patients with acute myocardial infarction and newly detected glucose abnormalities: predictive value of oral glucose tolerance test and HbA1c.

Karayiannides S, Djupsjö C, Kuhl J, Hofman-Bang C, ... Holzmann MJ, Lundman P
Background
Disturbances of glucose metabolism can be diagnosed by an oral glucose tolerance test (OGTT) and by glycated haemoglobin (HbA1c). The aim of this study was to investigate the association between newly detected disturbances of glucose metabolism and long-term prognosis after acute myocardial infarction (AMI) and to compare the predictive value of an OGTT and HbA1c.
Methods
Patients under the age of 80 years with no known history of diabetes admitted for AMI at the Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden, from January 1st, 2006 until December 31st, 2013, were investigated with an OGTT and a HbA1c before discharge and were classified as having normal glucose tolerance (NGT), prediabetes or diabetes according to American Diabetes Association (ADA) criteria. Using nationwide, all-inclusive registers, patients were followed for the incidence of combined event [CE (first of myocardial infarction, heart failure, ischaemic stroke or mortality)] for a mean follow-up time of 4.8 years. Cox regression analysis was used to calculate Hazard Ratios (HR) and their 95% confidence intervals (CI).
Results
Of the 841 patients who were investigated with both an OGTT and a HbA1c, 139 (17%) patients had NGT, 398 (47%) had prediabetes and 304 (36%) had diabetes according to OGTT. The corresponding figures using HbA1c were 320 (38%), 461 (55%) and 60 (7%). Patients with newly discovered diabetes were older and had a higher body mass index compared to those with NGT. OGTT was not predictive for CE. In contrast, prediabetes identified by a HbA1c was associated with an increased risk for CE (HR 1.31; 95% CI 1.05-1.63) compared to normoglycaemia. When comparing the prognostic value of different glucose and HbA1c cut-offs, only a HbA1c ≥ 39 mmol/mol was significantly associated with CE (HR 95% CI; 1.30:1.05-1.61).
Conclusion
In this single-centre study, in a recent contemporary cohort, we found that around two thirds of the patients admitted with AMI with no known history of diabetes had disturbed glucose metabolism, in accordance with previous studies. HbA1c in the prediabetes range, but not OGTT, added predictive value on the long-term outcome, in a cohort to whom a pathologic OGTT result was communicated with lifestyle advice.



Cardiovasc Diabetol: 13 Jun 2021; 20:122
Karayiannides S, Djupsjö C, Kuhl J, Hofman-Bang C, ... Holzmann MJ, Lundman P
Cardiovasc Diabetol: 13 Jun 2021; 20:122 | PMID: 34126971
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