Sex- and age-specific variations in cardiovascular risk factor clustering in a high-risk population from coastal China: a retrospective cohort study

Cardiovascular disease is the leading cause of death globally, with China bearing the largest burden. However, the clustering patterns of modifiable risk factors and the optimal definition of clinically meaningful clustering remain unclear. This retrospective cohort study included 30,407 high-risk individuals from coastal Fujian, China. Five modifiable risk factors were assessed: hypertension, diabetes, dyslipidaemia, overweight, and smoking. Logistic regression and Cox proportional hazards models were used to evaluate factors associated with risk factor clustering and incident cardiovascular events. Latent class analysis (LCA) was applied to identify distinct clustering phenotypes. Overall, 77.9% of participants presented with ≥ 2 risk factors. Men consistently had higher clustering rates than women, but the gap narrowed with age (21.1% points at < 55y vs. 6.3 at ≥ 65y), driven by a steady rise in women with increasing age. A threshold of ≥ 3 risk factors yielded a time-dependent association with cardiovascular events (hazard ratio [HR] = 2.19, 95% confidence intervals [CI] 1.69–2.83 at 1 year; 1.47, 95% CI 1.32–1.64 at 3 years; 1.22, 95% CI 1.06–1.41 at 5 years; P for time interaction < 0.001), whereas the conventional ≥ 2 cut-off was significant only at 1 year. LCA identified three distinct phenotypes, among which the multi-metabolic class—characterised by concurrent hypertension, diabetes, dyslipidaemia, and overweight—conferred the highest risk (HR = 1.581, 95% CI 1.363–1.834, P < 0.001), particularly pronounced in women (HR = 2.089, 95% CI 1.668–2.617, P < 0.001). Hypertension was the most prevalent risk factor (76.2%) and a core component of the multi-metabolic phenotype. In this high-risk coastal Chinese population, risk factor clustering exhibits distinct sex- and age-specific patterns. Notably, the ≥ 3 risk factor threshold, but not the conventional ≥ 2 cut-off, was significantly associated with cardiovascular events. The multi-metabolic phenotype confers the highest cardiovascular risk, particularly among women and younger individuals, with hypertension as the most prevalent modifiable risk factor. These findings underscore the urgent need for phenotype-guided, sex- and age-stratified prevention strategies in high-risk settings.