Cardiovascular Diabetology

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ISSN / EISSN : 1475-2840 / 1475-2840
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Jung-Chi Hsu, Yen-Yun Yang, Shu-Lin Chuang, Chih-Chieh Yu,
Published: 23 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-12; doi:10.1186/s12933-021-01341-3

Abstract:
Background Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Glycemic variability (GV) is associated with risk of micro- and macrovascular diseases. However, whether the GV can increase the risk of AF remains unknown. Methods The cohort study used a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 27,246 adult patients with T2DM were enrolled for analysis. Each individual was assessed to determine the coefficients of variability of fasting glucose (FGCV) and HbA1c variability score (HVS). The GV parameters were categorized into quartiles. Multivariate Cox regression models were employed to estimate the relationship between the GV parameters and the risk of AF, transient ischemic accident (TIA)/ischemic stroke and mortality in patients with T2DM. Results The incidence rates of AF and TIA/ischemic stroke were 21.31 and 13.71 per 1000 person-year respectively. The medium follow-up period was 70.7 months. In Cox regression model with full adjustment, the highest quartile of FGCV was not associated with increased risk of AF [Hazard ratio (HR): 1.12, 95% confidence interval (CI) 0.96–1.29, p = 0.148] or TIA/ischemic stroke (HR: 1.04, 95% CI 0.83–1.31, p = 0.736), but was associated with increased risk of total mortality (HR: 1.33, 95% CI 1.12–1.58, p < 0.001) and non-cardiac mortality (HR: 1.41, 95% CI 1.15–1.71, p < 0.001). The highest HVS was significantly associated with increased risk of AF (HR: 1.29, 95% CI 1.12–1.50, p < 0.001), total mortality (HR: 2.43, 95% CI 2.03–2.90, p < 0.001), cardiac mortality (HR: 1.50, 95% CI 1.06–2.14, p = 0.024) and non-cardiac mortality (HR: 2.80, 95% CI 2.28–3.44, p < 0.001) but was not associated with TIA/ischemic stroke (HR: 0.98, 95% CI 0.78–1.23, p = 0.846). The Kaplan–Meier analysis showed significantly higher risk of AF, cardiac and non-cardiac mortality according to the magnitude of GV (log-rank test, p < 0.001). Conclusions Our data demonstrate that high GV is independently associated with the development of new-onset AF in patients with T2DM. The benefit of maintaining stable glycemic levels to improve clinical outcomes warrants further studies.
Or Yosefy, Barucha Sharon, Chana Yagil, Mark Shlapoberski, Alejandro Livoff, Ilana Novitski, Ronen Beeri, , Chaim Yosefy
Published: 23 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-12; doi:10.1186/s12933-021-01347-x

Abstract:
Background Diabetic patients have an increased predisposition to thromboembolic events, in most cases originating from thrombi in the left atrial appendage (LAA). Remodeling of the LAA, which predisposes to thrombi formation, has been previously described in diabetic patients with atrial fibrillation, but whether remodeling of the LAA occurs in diabetics also in the absence of atrial fibrillation is unknown. To investigate the contribution of diabetes, as opposed to atrial fibrillation, to remodeling of the LAA, we went from humans to the animal model. Methods We studied by echocardiography the structure and function of the heart over multiple time points during the evolution of diabetes in the Cohen diabetic sensitive rat (CDs/y) provided diabetogenic diet over a period of 4 months; CDs/y provided regular diet and the Cohen diabetic resistant (CDr/y), which do not develop diabetes, served as controls. All animals were in sinus rhythm throughout the study period. Results Compared to controls, CDs/y developed during the evolution of diabetes a greater heart mass, larger left atrial diameter, wider LAA orifice, increased LAA depth, greater end-diastolic and end-systolic diameter, and lower E/A ratio—all indicative of remodeling of the LAA and left atrium (LA), as well as the development of left ventricular diastolic dysfunction. To investigate the pathophysiology involved, we studied the histology of the hearts at the end of the study. We found in diabetic CDs/y, but not in any of the other groups, abundance of glycogen granules in the atrial appendages , atria and ventricles, which may be of significance as glycogen granules have previously been associated with cell and organ dysfunction in the diabetic heart. Conclusions We conclude that our rodent model of diabetes, which was in sinus rhythm, reproduced structural and functional alterations previously observed in hearts of human diabetics with atrial fibrillation. Remodeling of the LAA and of the LA in our model was unrelated to atrial fibrillation and associated with accumulation of glycogen granules. We suggest that myocardial accumulation of glycogen granules is related to the development of diabetes and may play a pathophysiological role in remodeling of the LAA and LA, which predisposes to atrial fibrillation, thromboembolic events and left ventricular diastolic dysfunction in the diabetic heart.
Seyyed Saeed Moazzeni, Reyhane Hizomi Arani, Niloofar Deravi, Mitra Hasheminia, Davood Khalili, Fereidoun Azizi,
Published: 12 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-13; doi:10.1186/s12933-021-01326-2

Abstract:
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.
, Shweta Kapur, Sindhuri Benjaram, Zachary Cantor, Navid Mahabadi, Tanveer Mir, M. Safwan Badr
Published: 10 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-15; doi:10.1186/s12933-021-01336-0

Abstract:
Background The pleiotropic effects of statins may reduce the severity of COVID-19 disease. This study aims to determine the association between inpatient statin use and severe disease outcomes among hospitalized COVID-19 patients, especially those with Diabetes Mellitus (DM). Research design and methods A retrospective cohort study on hospitalized patients with confirmed COVID-19 diagnosis. The primary outcome was mortality during hospitalization. Patients were classified into statin and non-statin groups based on the administration of statins during hospitalization. Analysis included multivariable regression analysis adjusting for confounders and propensity score matching to achieve a 1:1 balanced cohort. Subgroup analyses based on presence of DM were conducted. Results In the cohort of 922 patients, 413 had a history of DM. About 27.1% patients (n = 250) in the total cohort (TC) and 32.9% patients (n = 136) in DM cohort received inpatient statins. Atorvastatin (n = 205, 82%) was the most commonly prescribed statin medication in TC. On multivariable analysis in TC, inpatient statin group had reduced mortality compared to the non-statin group (OR, 0.61; 95% CI, 0.42–0.90; p = 0.01). DM modified this association between inpatient statins and mortality. Patients with DM who received inpatient statins had reduced mortality (OR, 0.35; 95% CI, 0.21–0.61; p < 0.001). However, no such association was noted among patients without DM (OR, 1.21; 95% CI, 0.67–2.17; p = 0.52). These results were further validated using propensity score matching. Conclusions Inpatient statin use was associated with significant reduction in mortality among COVID-19 patients especially those with DM. These findings support the pursuit of randomized clinical trials and inpatient statin use appears safe among COVID-19 patients.
Jordi Real, Bogdan Vlacho, Emilio Ortega, Joan Antoni Vallés, Manel Mata-Cases, Esmeralda Castelblanco, Eric T. Wittbrodt, Peter Fenici, Mikhail Kosiborod, , et al.
Published: 9 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-11; doi:10.1186/s12933-021-01323-5

Abstract:
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.
, , Valentín Hernández-Barrera, , José M. de Miguel-Yanes, David Carabantes-Alarcon, Javier de Miguel-Diez,
Published: 9 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-14; doi:10.1186/s12933-021-01334-2

Abstract:
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.
Yong Zhu, Kesen Liu, Maolin Chen, Yan Liu, Ang Gao, Chengping Hu, Hong Li, Huagang Zhu, Hongya Han, Jianwei Zhang, et al.
Published: 8 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-12; doi:10.1186/s12933-021-01332-4

Abstract:
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.
, Scott Isom, Dana Dabelea, Ralph D’Agostino, Lawrence M. Dolan, Lynne Wagenknecht, Giuseppina Imperatore, Sharon Saydah, Angela D. Liese, Jean M. Lawrence, et al.
Published: 7 July 2021
Cardiovascular Diabetology, Volume 20, pp 1-10; doi:10.1186/s12933-021-01328-0

Abstract:
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.
Paola Caruso, Lorenzo Scappaticcio, Maria Ida Maiorino, Katherine Esposito,
Published: 6 July 2021
Cardiovascular Diabetology, Volume 20; doi:10.1186/s12933-021-01325-3

Abstract:
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.
Zhiyuan Wu, Di Zhou, Yue Liu, Zhiwei Li, Jinqi Wang, Ze Han, Xinlei Miao, Xiangtong Liu, Xia Li, Wei Wang, et al.
Published: 6 July 2021
Cardiovascular Diabetology, Volume 20; doi:10.1186/s12933-021-01330-6

Abstract:
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.
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