Non-HDL cholesterol mediates the association between atherogenic index of plasma and cardiometabolic multimorbidity in Chinese adults: a CHARLS cohort study

The atherogenic index of plasma (AIP) has recently been proposed as a novel indicator of dyslipidemia and is closely associated with the risk of cardiovascular disease. However, the relationship between AIP and cardiometabolic multimorbidity (CMM) has not been elucidated. This study aimed to determine the association between AIP and new-onset CMM, and to analyze the mediating role of non-high-density lipoprotein cholesterol (non-HDL-C) in this relationship. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). A total of 8,902 middle-aged and older adults (≥ 45 years of age) without CMM at baseline in 2011 were enrolled and followed until 2020. The baseline AIP level was the exposure variable, the baseline non-HDL-C level was the mediator, and new-onset CMM during the 2011–2020 follow-up period was the outcome variable. Cox proportional hazards models were used to evaluate the association between AIP and CMM. Bootstrap methods were used for mediation analysis to determine the mediating effect of non-HDL-C and subgroup analyses were performed to assess the robustness of the findings. By the end of follow-up in 2020, 883 participants (9.92%) had developed new-onset CMM. After full adjustment for confounders, each one-unit incremental increase in AIP was associated with a 70.9% increased risk of CMM (HR = 1.709, 95% CI: 1.399–2.087). Participants in the highest quartile had a 75.4% increased risk of CMM compared to the lowest AIP quartile (HR = 1.754, 95% CI: 1.410–2.183). Non-HDL-C partially mediated the association between AIP and CMM, accounting for 25.53% of the total effect (indirect effect, β = 0.014, 95% CI: 0.006–0.022, P < 0.001). Sensitivity analyses that excluded early CMM events or participants who died during follow-up yielded consistent results, which confirmed the robustness of our primary findings. Subgroup analyses indicated consistent associations across strata of age, sex, body mass index, hypertension, and lifestyle factors. An elevated AIP was independently associated with an increased risk of new-onset CMM among middle-aged and older Chinese adults with non-HDL-C partially mediating this association. AIP may serve as a reference indicator for identifying populations at high risk of CMM and provide insights for early prevention strategies.