Cardiovascular Diabetology最新文献

Background: Stroke is one of the advanced outcomes of cardiovascular kidney metabolic syndrome (CKM). The combined effects of inflammation, insulin resistance, and hypertension in stroke remain to be fully elucidated in population studies. This study investigates the association between the composite TyG inflammation index (c-reactive protein-triglyceride glucose index, CTI) and hypertension with long-term stroke.

Methods: This longitudinal cohort study included 9082 participants from the China Health and Retirement Longitudinal Study (CHARLS). The associations with stroke risk were assessed using Cox proportional hazards models and Kaplan-Meier analysis, while predictive performance was evaluated using ROC curves and time-dependent AUC. The contribution of each component was determined by Weighted Quantile Sum (WQS) regression. Subgroup analysis and sensitivity analysis were also conducted.

Results: Over a median 9-year follow-up, 811 (8.9%) incident stroke cases occurred. A significant dose-response relationship was observed, with the highest CTI-hypertension group exhibiting a fully adjusted hazard ratio of 3.19 (95% CI 2.62-3.88) for stroke compared to the lowest group. The combined CTI-hypertension model demonstrated superior predictive performance (AUC = 0.672) versus hypertension-alone (AUC = 0.661) or CTI-alone (AUC = 0.651) models. WQS analysis identified C-reactive protein (38.8%) and hypertension (31.7%) as the predominant risk factors.

Conclusion: Integrating CTI with hypertension significantly improves stroke risk stratification in CKM stage 0-3 populations, supporting its potential for early identification of high-risk individuals.

Background: Semaglutide has demonstrated the ability to reduce the risk of progression to type 2 diabetes in patients with myocardial infarction and overweight or obesity without diabetes. However, implementation of semaglutide treatment in daily clinical care is challenging due to costs and limited supply. Thus, it is essential to identify patients who are most likely to benefit from this treatment. Therefore, we aimed to investigate the 5-year risk of progression to type 2 diabetes in SELECT-eligible patients with a recent myocardial infarction and overweight or obesity without diabetes, and to assess the estimated preventive potential of semaglutide in a real-world cohort.

Methods: We included patients registered in the Western Denmark Heart Registry with first-time myocardial infarction and body mass index (BMI) ≥ 27 kg/m² without diabetes, thus meeting the eligibility criteria of the SELECT trial. The cohort was grouped by glycemic status at baseline: HbA1c 6.0-6.4% (prediabetes_6.0-6.4%), 5.7-6.4% (prediabetes_5.7-6.4%), or < 5.7% (normoglycemia). A Cox proportional hazards regression model was used to calculate cause-specific hazard ratios (HR), adjusted for sex, age, hypertension, and smoking. The main endpoint was progression to type 2 diabetes. The 5-year number-needed-to-treat (NNT₅) with semaglutide was estimated based on the SELECT trial.

Results: The cohort comprised 7398 patients with median follow-up of 4.7 (Q1-Q3 2.8-5.0) years. At baseline, 1385 (19%) patients had prediabetes_6.0-6.4%, 3751 (51%) had prediabetes_5.7-6.4%, and 3647 (49%) had normoglycemia. The median BMI was similar across the groups: 30 kg/m² (Q1-Q3 28-33), 30 kg/m² (Q1-Q3 28-32), and 29 kg/m² (Q1-Q3 28-31). The 5-year risks of progression to type 2 diabetes were 54%, 30%, and 5%, respectively. Compared with normoglycemia, those with prediabetes_6.0-6.4% were associated with an 18-fold increased risk of progression to type 2 diabetes (HR 18.3, 95% CI 15.2-22.1) and the estimated NNT₅ with semaglutide to prevent one case of type 2 diabetes was 2.7 in this subgroup.

Conclusions: In real-world patients with recent myocardial infarction and overweight or obesity, prediabetes was much stronger associated with progression to type 2 diabetes than previously reported in the SELECT trial. Further, we estimated that treatment with semaglutide might be able to substantially reduce progression to type 2 diabetes.

Background: The COLCOT trial showed that patients with diabetes may benefit from low-dose colchicine, suggesting a potential interplay between insulin resistance (IR) and inflammation. Whether their combined assessment improves mortality risk stratification in the general population remains unclear.

Methods: We analyzed 50,654 adults from NHANES 1999-2018 linked to the National Death Index. IR and inflammation were assessed using estimated glucose disposal rate (eGDR) and the log₂-transformed aggregate index of systemic inflammation (AISI), respectively. Survey-weighted Cox proportional hazards models were used for all-cause mortality. For cardiovascular (CVD) mortality, cumulative incidence functions (CIFs) were estimated with Gray's test for between-group comparisons, and Fine-Gray subdistribution hazard models were fitted treating non-CVD death as a competing event. Discrimination was assessed using time-dependent ROC curves at 5 and 10 years. Robustness was evaluated through sensitivity analyses excluding immune-modifying conditions/treatments, applying a 24-month lag, and excluding extreme absolute lymphocyte counts.

Results: Over a median follow-up of 120 months, 6,936 all-cause deaths and 2,170 CVD deaths occurred. Higher eGDR was inversely associated with mortality (all-cause HR per 1-unit increase 0.90, 95% CI 0.88-0.92; CVD sHR 0.88, 95% CI 0.85-0.91), whereas higher log₂(AISI) was positively associated (all-cause HR per doubling 1.10, 95% CI 1.06-1.15; CVD sHR 1.13, 95% CI 1.06-1.20). In joint analyses, participants with low eGDR (≤ 8.40) and high log₂(AISI) (> 7.98) had the highest risks of all-cause mortality (HR 1.58, 95% CI 1.38-1.81) and CVD mortality (cause-specific HR 2.09, 95% CI 1.58-2.77; Fine-Gray sHR 2.13, 95% CI 1.66-2.74), with graded separation of CIFs (Gray's test P < 0.001). The combined model showed improved discrimination (AUCs at 5/10 years: all-cause 0.705/0.723; CVD 0.754/0.769). Results were consistent across sensitivity analyses.

Conclusion: In a nationally representative U.S. cohort, eGDR and log₂(AISI) were independently and jointly associated with all-cause and CVD mortality. Their combined assessment improves risk stratification and may help identify individuals most likely to benefit from targeted preventive and anti-inflammatory strategies.

Background: Triglyceride‒glucose (TyG) related indices have been implicated in metabolic syndrome (MetS), cardiovascular disease (CVD), and mortality. However, their prospective associations with CVD and mortality among individuals with MetS remain limited.

Methods: In this large-scale prospective study, we included 113,699 UK Biobank participants with MetS who were free of CVD at baseline. The TyG index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), and TyG-waist-to-height ratio (TyG-WHtR) were calculated and categorized into quartiles. Cox proportional hazards models, restricted cubic splines, two-piecewise regression models, and K-means clustering were applied to evaluate the associations of TyG-related indices with CVD and mortality outcomes. Incremental predictive performance was further assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).

Results: Over a median follow-up of 13.7 years, higher quartiles of TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with all CVD outcomes. Among these indices, TyG-WC demonstrated the strongest associations, particularly for total CVD (hazard ratios [HRs] for the highest vs. lowest quartile: 1.42 [95% CI: 1.36-1.48]). For mortality outcomes, TyG-WC also exhibited the most pronounced associations, showing an HR of 1.51 (1.32-1.72) for CVD mortality. In contrast, the TyG index alone showed inverse associations with both CVD incidence and CVD mortality. Dose-response analyses revealed that TyG-related indices were linearly associated with coronary heart disease (CHD), whereas U- or J-shaped nonlinear relationships were observed for other CVD outcomes, with risks rising steadily beyond the identified inflection points. In predictive analyses, TyG-WC provided the greatest incremental predictive value for total CVD, all-cause mortality, and CVD mortality, while TyG-WHtR yielded the largest improvements for CHD and stroke. Moreover, results from trajectory analyses showed that participants with persistently high TyG-related trajectories had substantially elevated risks of CVD. All results remained robust across subgroup and sensitivity analyses.

Conclusions: TyG-BMI, TyG-WC, and TyG-WHtR were robust predictors of CVD and mortality in individuals with MetS. These indices exhibited nonlinear threshold effects and improved predictive performance, supporting their utility in clinical risk stratification.

Background: Insulin resistance and visceral adiposity are established pathophysiological drivers of cardiovascular disease (CVD). The triglyceride‒glucose (TyG) index and the Chinese visceral adiposity index (CVAI) are respective indicators of these conditions. However, the association of their combination, the TyG-CVAI, with the risk of new-onset CVD in the general population remains unclear. This study aimed to investigate this relationship using data from a large national cohort.

Methods: This prospective study included participants in the China Health and Retirement Longitudinal Study (CHARLS) who lacked CVD at baseline. The TyG-CVAI was calculated and used to categorize participants into quartiles. The primary endpoint was the incidence of new-onset CVD. Kaplan‒Meier analysis was performed to assess the cumulative incidence, while multivariable Cox proportional hazards models were used to estimate risk ratios (HRs) and 95% confidence intervals (CIs). The nonlinearity of the relationship was examined using restricted cubic splines (RCSs), and the predictive performance of the TyG-CVAI was evaluated and compared to that of its components using receiver operating characteristic (ROC) curve analysis.

Results: Among the 7977 participants, 1221 ultimately developed a CVD. Kaplan‒Meier analysis showed a significantly higher cumulative incidence of CVD with increasing TyG-CVAI quartiles (log-rank P < 0.001). After full adjustment for demographic, lifestyle, and cardiometabolic risk factors, participants in the highest quartile (Q4) had a significantly higher CVD risk (HR = 1.64, 95% CI 1.35-2.00) than those in the lowest quartile (Q1). RCS analysis revealed a significant nonlinear association between the TyG-CVAI and CVD risk, with a threshold at 778.62; below this point, no significant association was observed, whereas above it, each unit increase in the index conferred a 47% higher CVD risk (HR 1.47, 95% CI 1.31-1.64; P < 0.001). Furthermore, the TyG-CVAI (AUC = 0.6315) outperformed the TyG index (AUC = 0.5938) and the CVAI (AUC = 0.5851) alone in predicting the risk of CVD.

Conclusions: In this national cohort of middle-aged and older Chinese adults, a higher TyG-CVAI was independently and nonlinearly associated with an increased risk of new-onset CVD, demonstrating superior predictive value over its individual components. The TyG-CVAI may serve as a simple and effective integrated tool for the early identification of high-risk individuals for primary CVD prevention.

Background: Carotid plaques result from a blockage or narrowing of carotid arteries associated with severe atherosclerotic cardiovascular diseases. We aimed to assess the effect of marine n-3 fatty acid supplementation on carotid plaques among patients with diabetes and whether the effect was modified by genetics.

Methods: In this 14 month double-blind, randomized controlled trial, 415 patients with type 2 diabetes (T2D) were randomly assigned to receive high-dose (3.0 g/day) or low-dose (1.5 g/day) marine n-3 fatty acids (fish oil) or placebo (refined olive oil). The primary outcome was the prevalence of carotid plaques. Secondary outcomes included changes in NMR-derived lipoprotein subclasses. Genetic interactions with the supplementation were also explored.

Results: 383 participants (92.3%) completed the 14 month intervention, and 359 patients (86.5%) completed carotid ultrasound exams. Fish oil supplementation did not significantly reduce the carotid plaque prevalence (P trend = 0.111). Compared to the placebo, the odds ratios (95% CIs) of carotid plaque risk were 1.11 (0.56-2.22) and 0.54 (0.26-1.13) for low-dose and high-dose groups, respectively. Fish oil supplementation also showed no significant effect on the incidence of new carotid plaques (P for trend = 0.304) or the regression of existing plaques (P for trend = 0.390). High-dose intervention significantly reduced remnant cholesterol, LDL-1-triglycerides (TG), HDL-4-TG, and HDL-3-TG. In subgroups by genetic risk, the high-dose intervention significantly reduced carotid plaque risk specifically in patients with a low genetic risk for remnant cholesterol, with no significant benefit observed in those with medium or high genetic risk (P for interaction = 0.008; FDR = 0.056).

Conclusion: In patients with T2D, 14 month marine n-3 fatty acid supplementation does not reduce carotid plaque risk but improves lipoprotein profile. The anti-atherosclerotic effect appeared significant in patients with a low genetic risk of remnant cholesterol, warranting further investigation into personalized nutritional strategies.

Trial registration: Clinicaltrials.gov NCT03708887.

Up to 40-60% of patients undergoing coronary angiography because of angina and/or evidence of inducible ischaemia on non-invasive stress testing are diagnosed with ischaemia and non-obstructive coronary artery disease (INOCA). The pathogenesis of this condition is primarily attributed to two mechanisms: coronary microvascular dysfunction (CMD) and coronary vasospasm. Notably, ischaemic heart disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR), affecting 10-25% of the general adult population, plays a major role in the pathophysiology of T2DM, but can precede diabetes by years. IR is recognised as a major cardiovascular risk factor, involved in endothelial dysfunction and inflammation, two key processes leading to CMD and vasomotor dysfunction. Hyperinsulinaemia, dysglycaemia, and oxidative stress contribute to this complex relationship, yet the connection between IR, CMD and coronary vasospasm remains incompletely defined. Moreover, IR may represent a target for tailored therapies aimed at improving microvascular function and alleviating symptom burden. Although a few studies have investigated this relationship, the molecular mechanisms by which multiple pathways lead to different INOCA endotypes remain incompletely defined. The aim of this review is to summarise current evidence linking IR, CMD and coronary vasospasm, with emphasis on pathophysiological mechanisms and diagnostic approaches, and to highlight future research directions in this clinical setting.