[Association between novel high-density lipoprotein cholesterol metabolic phenotypes and all-cause and cardiovascular disease mortality in older adults in communities in Beijing].

Objective: To investigate the association of novel high-density lipoprotein cholesterol (HDL-C) metabolic phenotypes-metabolic HDL-C (mHDL-C) and its residual (mHDL-CΔ)-with all-cause and cardiovascular disease (CVD) mortality risks in community-dwelling older adults in Beijing. Methods: Based on the Beijing Healthy Aging Cohort Study, a total of 8 578 older adults (≥60 years) with complete baseline data were included and followed for survival outcomes. A random forest regression model was constructed to obtain mHDL-C and mHDL-CΔ. Cox proportional hazards regression models were used to analyze the associations of HDL-C, mHDL-C, and mHDL-CΔ with mortality risk. Predictive performance was evaluated using the net reclassification improvement (NRI), integrated discrimination improvement, and time-dependent area under the receiver operating characteristic curve. Results: In the follow up as of March 31, 2021, a total of 1 162 all-cause deaths occurred (the median survival: 2 257.50 days), including 558 CVD deaths. After adjusting for confounders, both HDL-C and mHDL-C levels were negatively associated with the all-cause mortality (HR=0.84, 95%CI: 0.79-0.91; HR=0.84, 95%CI: 0.76-0.91) and CVD mortality (HR=0.73, 95%CI: 0.65-0.81; HR=0.70, 95%CI: 0.61-0.80). In contrast, mHDL-CΔ was positively associated with both types of mortality (all-cause: HR=1.28, 95%CI: 1.17-1.40; CVD: HR=1.42, 95%CI: 1.25-1.61). mHDL-CΔ showed the best reclassification of all-cause mortality (NRI=0.122). Conclusions: In the older adults in communities in Beijing, the novel metabolic phenotypes mHDL-C and mHDL-CΔ were significantly associated with all-cause and CVD mortality risks. These indicators can reveal metabolic heterogeneity and residual mortality risk which cannot be detected by traditional HDL-C concentration, suggesting their potential as auxiliary predictors for mortality risk and as tools for cardiovascular risk stratification and precision prevention in this population.