Background
The emergence of the ‘SMuRF-less’ (absence of Standard Modifiable Risk Factors) phenotype challenges traditional cardiovascular disease (CVD) prediction models. While depression is an established CVD risk factor, its pathogenic role in the absence of hypertension, diabetes, hypercholesterolemia, and smoking remains unclear, especially regarding potential sex differences.
Methods
This prospective analysis included 2484 middle-aged and older adults (≥45 years) free of baseline CVD and all SMuRFs (hypertension, diabetes, hypercholesterolemia, smoking) from the China Health and Retirement Longitudinal Study. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association between depressive symptoms and CVD events after adjusting for potential confounders. Dose-response associations were examined using restricted cubic splines, and all analyses were stratified by sex.
Results
Over a median follow-up of 10.3 years, 523 CVD events occurred. Elevated depressive symptoms were associated with increased risks of CVD (adjusted HR = 1.47, 95% CI: 1.22–1.77), stroke (HR = 1.61, 95% CI: 1.13–2.28), and heart disease (HR = 1.42, 95% CI: 1.16–1.74) in the overall population. However, stratified analysis revealed this association was entirely driven by women, with significant risks for CVD (HR = 1.50, 95% CI: 1.22–1.86) and stroke (HR = 2.08, 95% CI: 1.35–3.21). No significant association was observed in men. A linear negative association was evident in women but not in men.
Conclusions
In this SMuRF-less cohort, depressive symptoms independently predicted incident CVD, with the association being particularly strong in women. Our findings identify a “SMuRF-less but depressed” women phenotype that warrants targeted attention in primary prevention.
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