Age-dependent threshold effect of reproductive lifespan on cardiovascular disease in chinese women: a CHARLS cohort study

Reproductive lifespan (RLS) reflects lifetime estrogen exposure. Whether age modifies the nonlinear link between RLS and cardiovascular disease (CVD) is unclear. We investigated this age-dependent relationship in Chinese women. Data were from CHARLS. We included 4,443 women aged ≥ 45 years without CVD at baseline (2011). Incident CVD was defined as self-reported, physician-diagnosed heart disease or stroke. RLS = menopause age − menarche age. Participants were stratified by baseline age tertiles. We applied Cox models with restricted cubic splines and two-piecewise Cox regression to detect nonlinearity and thresholds, with subgroup and sensitivity analyses. Over 7.53 years of follow-up (33,442 person-years), 1,244 (28.0%) developed CVD. In the youngest tertile (age 45–55), RLS showed a U-shaped association with a threshold at ~ 31 years (LRT P = 0.027). Above 31 years, longer RLS increased CVD risk (HR = 1.08, 95% CI 1.03–1.13; P = 0.003). No thresholds were detected in older tertiles. Findings were robust in sensitivity analyses. In younger postmenopausal women, RLS beyond ~ 31 years was associated with higher CVD risk. These findings are hypothesis-generating and require confirmation; whether reproductive lifespan improves cardiovascular risk prediction remains to be formally evaluated.