Cardiovascular Diabetology最新文献

Background: Diabetic patients undergoing percutaneous coronary intervention (PCI) frequently have complex coronary artery disease (CAD) and suboptimal outcomes with drug-eluting stents (DES). Sirolimus-coated balloons (SCB) have recently been introduced, but comparative data versus DES in diabetic patients with de novo CAD are lacking.

Methods: The SIMPLE-DM study is a pooled analysis of five observational registries including all-comer diabetic patients undergoing PCI for de novo CAD. Patients in the SCB cohort were treated with the phospholipid nanocarrier Magic Touch SCB, while those in the DES cohort received current-generation DES. Propensity score (PS) adjustment was used to balance clinical and angiographic characteristics. The primary endpoint was the 2-year cumulative incidence of target lesion failure (TLF), defined as the composite of cardiac death, target vessel MI (TV-MI), or target lesion revascularization (TLR).

Results: A total of 1838 patients were included, 599 treated with SCB-based PCI and 1239 with DES-only PCI. At 2 years, TLF occurred in 9.1% of SCB and 9.9% of DES patients (adj. hazard ratio HR 0.88, 95% confidence interval CI 0.43-1.81, p = 0.736). No significant differences were found in cardiac death, TV-MI or TLR. SCB-based PCI was associated with more favourable outcomes in patients with chronic kidney disease (p for interaction = 0.042) and long lesions (p for interaction = 0.003), whereas DES-only PCI performed better in those with short lesions.

Conclusions: In diabetic patients undergoing PCI for de novo CAD, an SCB-based strategy was associated with comparable 2-year outcomes to DES-only PCI, with signals of potential benefit in the highest clinical and anatomical risk subsets.

Background: Prediabetes, an intermediate metabolic state preceding diabetes, independently accelerates cardiovascular pathology through dysglycemia-driven mechanisms. This study evaluates the heterogeneous cardiovascular risk stratification by directly comparing two major diagnostic criteria (ADA vs. WHO/IEC) and assesses the causal cardiovascular consequences of prediabetes, an area requiring further elucidation.

Methods: After excluding participants with baseline cardiovascular disease, the remaining cohort with complete glycemic and relevant assessment data (n = 278,697) was stratified into normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM). Prediabetes was subsequently classified according to both ADA (fasting plasma glucose, FPG 5.6-6.9 mmol/L and/or glycosylated hemoglobin A1c, HbA1c 5.7-6.4%) and WHO/IEC (FPG 6.1-6.9 mmol/L and/or HbA1c 6.0-6.4%) criteria. Associations with incident cardiovascular disease (CVD), mortality, and cardiac remodeling (via cardiac magnetic resonance, CMR) were assessed using multivariable-adjusted models. Mendelian randomization (MR) tested causality of prediabetes on outcomes. All observational analyses were adjusted for key demographic, lifestyle, and clinical covariates.

Results: Over 13.5 years, prediabetes-irrespective of criteria-elevated CVD risk (ADA: HR = 1.14, 95% CI 1.12-1.16; WHO/IEC: HR = 1.23, 95% CI 1.19-1.27), with stronger mortality associations in WHO/IEC-defined individuals. MR analyses confirmed that prediabetes was causally associated with increased CVD (OR 1.01, 95% CI 1.01-1.02), coronary heart disease (OR 1.09, 95% CI 1.02-1.17), myocardial infarction (OR 1.12, 95% CI 1.06-1.19), stroke (OR 1.06, 95% CI 1.02-1.10), and primary hypertension (OR 1.01, 95% CI 1.01-1.02) risks. In an exploratory CMR substudy (n = 2512), early concentric left ventricular remodeling was suggested, particularly under WHO/IEC criteria. Risks were consistently observed across genetic susceptibility strata, though the lack of significant interaction warrants cautious interpretation and further investigation into potential effect modifications.

Conclusion: These findings highlight the differential prognostic utility of ADA and WHO/IEC criteria for cardiovascular risk stratification in prediabetes.

Background: Patients with chronic kidney disease (CKD) and coronary artery diseases (CAD) have a poor long-term prognosis. Although insulin resistance (IR) and systemic inflammation are well-established drivers of cardiovascular risk, the prognostic value of their composite assessment across the glycemic spectrum in patients with CKD and CAD remains undetermined. This study aimed to evaluate the prognostic utility of composite IR-inflammation biomarkers for predicting mortality in patients with CKD and CAD stratified by glycemic status.

Methods: 1353 patients with CKD and CAD were enrolled from National Health and Nutrition Examination Survey (NHANES) data (1999-2018). Composite biomarkers (TyG-hsCRP, TyG-CRP, and C-reactive Protein-Triglyceride Glucose Index [CTI]) were calculated. Patients were categorized by glycemic status (normoglycemia, prediabetes, diabetes) based on WHO/IEC criteria. The endpoint was all-cause and cardiovascular disease (CVD) death. Statistical analyses included Cox regression, Nelson-Aalen cumulative hazard plots with Log-rank test, restricted cubic splines, ROC curves, and reclassification metrics, adjusted for demographics, comorbidities, and treatments. Subgroup and sensitivity analyses ensured robustness.

Results: Over a median follow-up of 63-months, 744 all-cause and 323 CVD deaths occurred. Adjusted models showed elevated composite indices linked to higher mortality (e.g., CTI HR 1.43 [95% CI 1.24-1.65] for all-cause; HR 1.32 [1.06-1.64] for CVD). CTI provided good discrimination (AUC 0.700) and reclassification (IDI 0.010; NRI 0.196 for all-cause). The predictive utility of all three composite biomarkers was most pronounced in patients with diabetes, whereas CTI retained the strong association with all-cause mortality in normoglycemic and prediabetic patients. Risk stratification using both CTI and glycemic status identified patients with diabetes and high CTI as having the highest all-cause (HR 1.63 [1.22-2.17]) and CVD (HR 1.37 [0.88-2.14]) death risk.

Conclusion: Composite biomarkers integrating IR and inflammation, particularly CTI, significantly enhance mortality prediction in patients with CKD and CAD. The predictive utility is modulated by underlying glycemic status, enabling refined risk stratification and potentially guiding tailored management strategies for this complex patient population.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic disorders, and cardiovascular disease is the leading cause of death among affected individuals. Identifying simple biomarkers that capture metabolic-inflammatory burden and predict long-term mortality in MASLD remains a clinical priority. The C-reactive protein-triglyceride-glucose index (CTI) integrates inflammation, dyslipidaemia, and glycaemic status, but its relevance to MASLD and long-term mortality has not been fully elucidated.

Methods: We conducted a multi-stage investigation using two nationally representative cohorts from the United States and China. Cross-sectional associations between CTI and MASLD were assessed in the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS). Prospective associations of CTI with cardiovascular and all-cause mortality among participants with MASLD were examined utilising multivariable Cox proportional hazards models, restricted cubic splines, threshold analyses, and competing risk models. Causal mediation analyses were performed to measure the mediating functions of diabetes, hypertension, and body mass index. Extensive sensitivity analyses using alternative MASLD definitions and analytic strategies were conducted to assess robustness. Results from NHANES were externally validated in CHARLS.

Results: Higher CTI levels were strongly and nonlinearly associated with the presence of MASLD in both cohorts. Among individuals with MASLD, elevated CTI was associated with significantly increased risks of all-cause and cardiovascular mortality. Each unit increase in CTI in NHANES was linked to a 57% increased risk of cardiovascular death (HR 1.57, 95% CI 1.24-1.99) and a 47% increased risk of all-cause death (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.28-1.69) in fully adjusted models. A pronounced threshold effect was observed, with mortality risk rising sharply once CTI exceeded approximately 5.6. Consistent associations with all-cause mortality were observed in CHARLS. Mediation analyses indicated that diabetes accounted for a substantial proportion of the association between CTI and mortality, whereas body mass index played a minimal mediating role.

Conclusions: CTI is a robust metabolic-inflammatory marker associated with MASLD and long-term all-cause and cardiovascular mortality across diverse populations. The strong mediating role of diabetes underscores the central importance of glycaemic dysfunction in cardiometabolic risk. As a readily obtainable index, CTI may aid in cardiometabolic risk stratification among individuals with MASLD.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used therapies for cardiovascular risk reduction in type 2 diabetes (T2D). With the emergence of the SURPASS-CVOT trial, tirzepatide (a dual GIP/GLP-1 receptor agonist) has entered the therapeutic landscape; however, its comparative effect on cardiovascular outcomes compared to placebo and individual GLP-1RAs remains undefined.

Methods: We conducted a systematic review and frequentist network meta-analysis (NMA) of RCTs enrolling adults with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular (CV) risk. Eligible RCTs evaluated tirzepatide or GLP-1RAs and reported major adverse cardiovascular events (MACE), CV mortality, all-cause mortality, non-fatal myocardial infarction (MI) or non-fatal stroke. A class-level NMA was conducted to estimate the incremental benefit of tirzepatide and GLP-1RAs over placebo, and an agent-level NMA was conducted to explore differences between tirzepatide and individual GLP-1RA agents. Subgroup analyses, including established cardiovascular disease populations, and leave-one-out sensitivity analyses were performed.

Results: Eleven trials met inclusion criteria (10 GLP-1RA trials and 1 tirzepatide trial [SURPASS-CVOT]). In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo. Formal statistical comparisons between tirzepatide and the GLP-1RA class could not be performed within the constraints of the NMA; however, point estimates across outcomes numerically favored tirzepatide compared with placebo. In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97). Subgroup and sensitivity analyses did not substantially change point estimates.

Conclusion: Among adults with T2D and established ASCVD or high CV risk, class-level analysis demonstrated that tirzepatide significantly reduced the risk of cardiovascular events compared to placebo; at the agent-level, tirzepatide demonstrated comparable efficacy to individual GLP-1RAs. These findings suggest that tirzepatide provides cardiovascular benefit at least comparable to established GLP-1RAs, supporting its emerging role in cardiovascular risk reduction in T2D.

Background & aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to atherosclerotic cardiovascular disease (ASCVD). Markers of arterial stiffness and subclinical atherosclerosis (carotid-femoral pulse wave velocity [cfPWV], and carotid-intima media thickness [CIMT]) and endothelial dysfunction (flow-mediated dilation [FMD], nitroglycerine-induced dilation [NID]) are potential ASCVD predictors. This study examined the correlation between vasculopathy and MASLD in type 1 diabetes (T1D).

Methods: We conducted cross-sectional vascular assessments in non-smoking adults with T1D without ASCVD. MASLD was determined by ultrasound and transient elastography. FIB-4 was calculated as a marker of fibrosis. ASCVD risk scores were assessed using the Steno Type 1 Risk Engine. Subjects were included in a 2:1 control-to-case ratio and matched for age and diabetes duration.

Results: We examined 105 subjects, of whom 30 had MASLD. Mean age was 51.7 ± 15.7 years, mean diabetes duration was 29.9 ± 14.3 years. 50% were male, mean HbA1c was 55.1 ± 9.5 mmol/mol (7.2 ± 0.9%). MASLD was associated with lower NID (15.3 ± 6.3 vs. 20.1 ± 7.5%, p = 0.003). NID and cfPWV were more often impaired in people with MASLD (53.3% vs. 28.4%, p = 0.018, 56.7% vs. 35.1%, p = 0.043, respectively). In adjusted multivariable logistic regression, MASLD was associated with increased cfPWV (OR 8.30, 95% CI 1.25-55.2, p = 0.029), as was age, sex and mean arterial pressure. cfPWV and CIMT strongly correlated with 5-year ASCVD risk (cfPWV ρ = 0.76, CIMT ρ = 0.81, p < 0.001), as did FIB-4 (ρ = 0.74, p < 0.001). CIMT (0.93), cfPWV (0.88) and FIB-4 (0.88) yielded the highest AUROC to identify significant ASCVD risk.

Conclusions: cfPWV is the most robust vascular marker associated with MASLD in people with T1D. cfPWV, CIMT and FIB-4 correlated strongly to incident 5-year ASCVD risk. Sven Francque, Hilde Heuten and Christophe De Block have claimed equal senior authorship.