Remnant cholesterol and body mass index jointly associate with cardiometabolic Multimorbidity with mediation analysis...

Remnant cholesterol (RC) has emerged as a novel lipid parameter reflecting the residual risk of atherogenic dyslipidemia beyond low-density lipoprotein cholesterol (LDL-C). Previous studies have demonstrated that elevated RC and increased body mass index (BMI) are each independently associated with cardiometabolic diseases such as diabetes and cardiovascular disorders. However, whether RC interacts with BMI and how their combined influence contributes to the development of cardiometabolic multimorbidity (CMM)-the coexistence of multiple cardiometabolic conditions-remain unclear. Clarifying these relationships may provide new insights into the metabolic mechanisms underlying multimorbidity and improve early risk stratification. This longitudinal cohort study used data from 6,646 adults aged ≥ 45 years in the China Health and Retirement Longitudinal Study (CHARLS). Cardiometabolic multimorbidity (CMM) was defined as having two or more physician-diagnosed conditions among heart disease, stroke, and diabetes. Associations of remnant cholesterol (RC) and body mass index (BMI) with CMM were examined using restricted cubic spline, multivariable regression, interaction, and bidirectional mediation analyses, adjusting for demographic, lifestyle, and metabolic factors. A total of 6,646 participants (mean age 58.52 years) were included. Both RC and BMI were significant independent risk factors for CMM with combined, with a joint association. Elevated RC (≥ median) significantly increased the risk of CMM (adjusted OR = 1.35, p = 0.003), whereas BMI showed a dose-dependent risk pattern, with adjusted ORs (95% CIs) of 1.32 (1.10-1.58) for overweight and 1.78 (1.42-2.22) for obesity compared with normal weight (p < 0.01). The combined effect of high RC and high BMI significantly increased CMM risk (adjusted OR = 2.23, p < 0.0001). In adjusted mediation models, BMI accounted for 32.6% of the total association of RC on CMM (β = 0.00021, P < 0.001), whereas RC accounted for 6.9% of the total effect of BMI on CMM (β = 0.00005, P = 0.016). This study suggests that elevated remnant cholesterol and higher BMI are jointly associated with increased cardiometabolic multimorbidity risk, underscoring the importance of considering lipid-related and metabolic factors together in risk stratification.