Cardiovascular Diabetology最新文献

Background: Visceral obesity contributes to hypertension through pathways of insulin resistance and inflammation. The joint association of C-reactive protein-triglyceride-glucose index (CTI), which integrates these pathways, and anthropometric indices with incident hypertension remains unclear, especially across different baseline blood pressure.

Methods: The data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS) across the 2011 to 2020 survey waves. Participants were stratified based on the median values of anthropometric indices and CTI. The associations with incident hypertension risk were evaluated using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic spline (RCS) methods. Predictive performance was assessed by receiver operating characteristic (ROC) curve analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Mediation and interaction analyses were conducted to explore potential mediating effects and the robustness of the findings.

Results: Among 4,735 eligible participants, the median age was 56 years, and 46.04% were male. During the 9-year follow-up period, 1,852 participants (39.37%) developed hypertension. Cox regression analysis revealed that Compared with subjects with lower levels of both anthropometric indices and CTI, those with higher levels of both exhibited the highest risk of hypertension. Individuals with both BRI and CTI above the median consistently exhibited the highest risk of hypertension across all subgroups: HR = 1.51, 95% CI: 1.33-1.71 in the total population; HR = 1.58, 95% CI: 1.29-1.93 in the normal BP group; and HR = 1.45, 95% CI: 1.23-1.71 in the elevated BP group. After incorporating anthropometric indices and CTI into the basic model, the predictive performance for hypertension was significantly improved. The integrated model of BRI and CTI demonstrated the best overall predictive performance (AUC = 0.747). Mediation analysis revealed that CTI significantly mediated the association between anthropometric indices and hypertension.

Conclusion: These anthropometric indices and CTI effectively predicted hypertension risk across populations with different baseline blood pressures, both independently and in combination. Among all evaluations, the combination of BRI and CTI emerged as the optimal approach, most robustly associated with incident hypertension and providing the greatest improvement in risk discrimination and reclassification.

Background: Diabetes is associated with a high incidence of diabetic foot and peripheral artery disease and with markedly increased lifetime amputation risk. Here we investigated predictors of reamputation risk and mortality including antidiabetic medication in patients undergoing non-traumatic lower limb amputation (LLA).

Methods: In an observational longitudinal study, we analyzed 607 patients with diabetes and 500 patients without diabetes who underwent non-traumatic LLA between 2006 and 2022. The primary endpoint was reamputation-free survival. Predictors of subsequent amputations or mortality were analyzed using Cox regression and joint frailty models.

Results: Diabetes was independently associated with increased combined reamputation and mortality risk (HR 1.28, 95% CI [1.08, 1.52], p = 0.004). Reduced reamputation-free survival in patients with diabetes was triggered by a marked higher reamputation risk. Higher HbA1c levels were associated with lower reamputation-free survival. Older age, presence of atrial fibrillation and chronic kidney disease were associated with increased reamputation risk in patients with diabetes. Metformin usage in patients with type 2 diabetes was associated with a marked reduction in combined risk of reamputation and mortality (HR 0.59, 95% CI [0.43, 0.81] p = 0.001). While overall sodium-glucose transporter 2 inhibitor (SGLT2i) usage was low in this cohort, it was associated with an increased reamputation risk (HR 2.00, 95% CI [1.47, 2.72], p > 0.001) although safe with respect to mortality. Over time, reamputation risk peaked between 2020 and 2022, whereas mortality declined compared with the period from 2006 to 2010 in patients with diabetes.

Conclusion: Diabetes remains to be associated with reduced reamputation-free survival; an association that is independent of increased prevalence of comorbidities in our data. Although reamputation risk has increased in recent years, overall survival has improved in patients with diabetes. Metformin usage is associated with improved reamputation-free survival while our limited data suggest increased risk of reamputation but safety with respect to mortality in patients treated with SGLT2i. Further studies are warranted to evaluate the effect of SGLT2i therapy on outcome in patients undergoing LLA.

Succinate has recently emerged as a signaling metabolite that extends beyond its canonical role in the tricarboxylic acid (TCA) cycle to influence cellular adaptation and stress responses. In their study, Jia et al. identify the succinate-GPR91 axis as a key regulator of cardiomyocyte metabolic reprogramming and NAD⁺ homeostasis in heart failure with preserved ejection fraction (HFpEF). Their findings suggest that restoring succinate-GPR91 signaling enhances mitochondrial energetics, improves redox balance, and alleviates diastolic dysfunction. This commentary discusses the significance of these results in the broader context of cardiometabolic disease, highlighting the conceptual novelty of metabolic rewiring as a form of cardioprotection, while also addressing unresolved questions regarding tissue specificity, long-term signaling balance, and translational potential. In recent years, succinate has emerged as a multifaceted player not merely a tricarboxylic acid (TCA) cycle intermediate but also a stress‑responsive metabolite that conveys cellular metabolic state to neighbouring cells and distant tissues. It accumulates during ischemia, hypoxia, or mitochondrial dysfunction and can drive reverse electron transport at complex I, thereby increasing reactive oxygen species (ROS) production [1, 3]. This biochemical duality on the one hand enabling damaging ROS generation, and on the other acting extracellularly via the G protein-coupled receptor GPR91-raises a central question: is succinate-GPR91 signaling protective, maladaptive, or fundamentally context‑dependent? Demonstrating that succinate can act extracellularly through GPR91 to reprogram cardiac metabolism would recast it from a metabolic by‑product into a bona fide signaling molecule with therapeutic implications. In this issue, Jia et al.² provide compelling evidence that the succinate-GPR91 axis functions as a molecular conduit linking mitochondrial metabolism to cardiomyocyte energy reprogramming, restoring NAD + and attenuating diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF).

Background: Ambient air pollution has been linked to atrial fibrillation (AF), yet the underlying metabolic mechanisms remain poorly understood.

Methods: We analyzed 227,324 UK Biobank participants without baseline AF. We constructed an air pollution score by aggregating all four pollutants (PM_2.5, PM₁₀, NO₂, NO_x). Nuclear magnetic resonance metabolomics identified a pollution-related metabolic signature through elastic net regression. Associations between air pollutants, the metabolic signature and AF were analyzed using Cox models. Mediation analysis was employed to examine the role of the metabolic signature in the association between air pollutants and AF.

Results: During follow-up, 16,235 participants (7.14%) developed AF. We identified 65-metabolite signature significantly associated with air pollution, predominantly comprising lipoprotein lipid concentrations (32.31%), lipoprotein subclasses (15.38%), fatty acids (13.85%), and amino acids (12.31%). Each standard deviation increase in this metabolic signature was associated with 18% higher AF risk (HR = 1.18, 95%CI:1.03-1.35). The metabolic profile mediated 15.45% of the relationship between air pollution and AF, with lipoprotein parameters showing the strongest mediation effects.

Conclusion: Air pollution-related metabolic signature was independently associated with AF risk and mediated a significant portion of pollution's arrhythmogenic effects. These findings provide novel insights into biological mechanisms linking environmental exposures to AF.

Recent real-world evidence comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) with pioglitazone indicates broadly comparable cardiovascular and hepatic outcomes in individuals with type 2 diabetes, with a lower risk of heart failure among GLP-1RA users. These findings must be interpreted in the context of contemporary guidelines, which increasingly prioritize therapies with cardiometabolic benefits while restricting the role of pioglitazone to selected settings. Despite recognized adverse effects, pioglitazone retains clinical relevance due to its glycaemic efficacy, potential cardio-hepatic benefits, and low cost, particularly in health-care systems with limited access to newer agents. Rather than being interchangeable, pioglitazone and GLP-1RA occupy complementary positions within the current therapeutic landscape, underscoring the importance of individualized treatment selection.

Background: A newer and novel index, the Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index, has been proposed as a potential index for metabolic disorders. However, research on the relationship between CHG changes and cardiovascular disease (CVD) is limited. Our research aims to investigate the association between cumulative exposure and dynamic trajectories of CHG and cardiovascular disease risk.

Methods: Participants aged 45 and older were recruited from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reported description. K-means clustering analysis was used to classify dynamic CHG changes, and cumulative CHG (cuCHG) was calculated as follows: cuCHG=(CHG₂₀₁₂ + CHG₂₀₁₅)/time interval (2012-2015). Cox proportional hazards regression and restricted cubic spline (RCS) regression models were conducted to evaluate the association between cumulative exposure and dynamic trajectories of CHG and CVD risk.

Results: A total of 6,171 participants were included in the study, among whom 1,136 (18.4%) experienced incident of CVD. The risk of CVD increased with higher levels of cuCHG. K-means clustering indicated three distinct trajectories CHG variation. Compared to the stable reference group (Cluster 3), participants in the high-risk slowly increasing trajectory (Cluster 2) had a significantly higher risk of CVD (HR = 1.28, 95%CI: 1.10-1.49, P = 0.002). However, the moderate-decreasing trajectory (Cluster 1) was not significantly associated with CVD risk (HR = 1.09, 95%CI: 0.98-1.21, P = 0.126). In the Cox regression analysis, compared with the lowest quartile (Q1), participants in the highest quartile (Q4) had a significantly increased risk of CVD by 22% (HR = 1.22, 95% CI: 1.06-1.40, P = 0.005, adjusted P = 0.007). Furthermore, CVD risk increased progressively across ascending cuCHG quartiles (P for trend < 0.05). RCS analysis demonstrated a linear association between cuCHG and CVD risk (for overall, P < 0.001).

Conclusion: Our research indicates that both cuCHG and CHG changes are associated with CVD risk in middle-aged and older adults, particularly for those with consistently high-risk CHG levels, which are linked to a significantly increased CVD risk. In clinical practice, monitoring long-term CHG changes and maintaining relatively stable levels may help prevent CVD in this population.