Discordance between remnant cholesterol and LDL-C associated with the risk of new-onset cardiometabolic multimorbidity: A prospective cohort study

Remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) are widely recognized for their distinct roles in cardiovascular disease risk, yet their combined influence on cardiometabolic outcomes remains insufficiently studied. This study aimed to investigate the association of cumulative remnant cholesterol (CumRC) exposure and the discordance between RC and LDL-C with the incidence of cardiometabolic multimorbidity (CMM). All data for this study were obtained from the China Health and Retirement Longitudinal Study. CumRC was calculated as the average of RC values measured during waves 1 and 3, divided by the total exposure duration. The discordance between RC and LDL-C was defined as the difference in percentile units (>15 units). Cox proportional hazards models, along with subgroup and sensitivity analyses, were used to evaluate the associations between CumRC, the discordance between RC and LDL-C, and CMM risk. A total of 5867 participants without CMM were recruited from China Health and Retirement Longitudinal Study 2011 and followed up in 2018. Over a 7-year follow-up period, 435 participants developed CMM. Higher CumRC levels were associated with an increased risk of CMM. Comparing the extreme quartiles of CumRC, the hazard ratio (HR) for CMM was 1.77 (95% confidence interval CI: 1.31–2.40). After adjusting for traditional risk factors, each 10 mg/dL increase in CumRC was associated with a 3% higher risk of CMM (HR: 1.03, 95% CI = 1.01–1.04). In the discordance analysis, the discordantly high RC group showed a higher risk of CMM (HR: 1.31, 95% CI = 1.04–1.64) compared to those with higher LDL-C. This association held even among individuals with well-controlled LDL-C levels. The results remained robust across various sensitivity analyses. Elevated CumRC exposure is associated with an increased risk of CMM. Discordantly high RC, not discordantly high LDL-C, is significantly associated with CMM onset among Chinese adults.