Cumulative remnant cholesterol exposure during young adulthood and middle age and risk of cardiovascular events: A 30-year population-based cohort study

Remnant cholesterol (RC) is recognized as a residual risk factor for cardiovascular diseases (CVD). Most studies on the association between RC and CVD have focused on RC level at a single time point, typically during middle or older age. Limited data have characterized long-term RC exposures among young adult. Here we aimed to investigate the association of cumulative RC exposure during young adulthood and middle age with incident CVD later in life. This cohort study enrolled 3416 CARDIA (Coronary Artery Risk Development in Young Adults) participants aged 18–30 years. Cumulative RC exposure was determined as cumulative RC and time-weighted average (TWA) RC during young adulthood and middle age. Multivariable Cox proportional hazards models were employed to examine the association between cumulative RC exposure and incident CVD. Of the 3416 included participants, 193 (5.6%) primary CVD outcomes occurred with a median 30.4-year follow-up. In multivariable Cox proportional hazards regression models that adjusted for LDL-C level, the most recent RC level and other CVD risk factors, the hazard ratios for primary CVD ourtcomes were as follows: 2.01 (95% CI, 1.23–3.27; P for trend = 0.021) for cumulative RC, and 2.11 (95% CI, 1.28–3.47; P for trend = 0.011) for TWA RC. Similar results were observed in other secondary outcomes. Greater exposures to cumulative RC and TWA RC during young adulthood and middle age were independently associated with an increased risk of cardiovascular events, suggesting that maintaining low RC levels early in life may reduce the lifetime CVD risk. •Long-term cumulative RC exposure during young adulthood and middle age were associated with cardiovascular events.•This association was independent of LDL-C level, the most recent RC level and other CVD risk factors.•It suggests that achieving and maintaining optimal RC levels early in life may reduce the lifetime CVD risk.