Cumulative remnant cholesterol predicts cardiovascular outcomes in elderly patients with atherosclerotic cardiovascular disease

Aims Remnant cholesterol (RC) reportedly mediates residual cardiovascular risk in atherosclerotic cardiovascular diseases (ASCVD). However, few studies have characterized long-term cumulative RC exposure among elderly people. The study aimed to evaluate the association between cumulative exposure to RC and incident major adverse cardiovascular events (MACE) by analysing a cohort of elderly patients with ASCVD.Methods and results This retrospective multicentre cohort study enrolled ASCVD participants aged >= 75 years with baseline visits occurring from 2006 to 2012 followed by four in-person visits. Cumulative RC was estimated as the area under the curve using measurements from the first to fourth visits by using 9-year data. The time-weighted average (TWA) RC was expressed as cumulative exposure to RC averaged by years. All outcomes were follow-up from the fourth visit to the year 2021. Outcomes included a composite of MACE (stroke, unstable angina pectoris, myocardial infarction, and cardiac death). We included 4,680 participants (73.1% male, mean age 79.3 +/- 2.5 years). The median follow-up duration was 6.1 years (interquartile range: 3.4-6.6 years). In the multivariable model adjusted for traditional cardiovascular risk factors, low-density lipoprotein cholesterol level, and most recent RC level, the hazard ratios for MACE that compared the high and low tertiles of the RC variables were 1.30 [95% confidence interval (CI), 1.16-1.44] for cumulative RC and 1.36 (95% CI, 1.23-1.52) for TWA RC. Consistent significant associations were observed among most propensity score analyses.Conclusions Long-term cumulative RC was independently associated with incident MACE in elderly participants with ASCVD, suggesting that achieving and maintaining optimal RC levels later in life may still improve cardiovascular outcomes. This retrospective multicentre cohort study, enrolling 4680 participants aged >= 75 years with pre-existing atherosclerotic cardiovascular diseases (ASCVD), found that greater cumulative exposure to remnant cholesterol (RC) across a 9-year span was independently associated with an increased incidence of cardiovascular events, suggesting that cumulative RC may be a powerful predictor of cardiovascular outcomes in patients with ASCVD. Graphical Abstract Cumulative remnant cholesterol predicts cardiovascular outcomes in elderly patients with atherosclerotic cardiovascular disease. Models adjusted for age, sex, body mass index, smoking status, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes status, use of lipid-lowering and antihypertensive medications, and estimated remnant cholesterol levels at the last visit. Major adverse cardiovascular events were defined as a composite of stroke, unstable angina pectoris, myocardial infarction, and cardiac death. CI, confidence interval; MACE, major adverse cardiovascular events; RC, remnant cholesterol; TWA, time-weighted average.