The mediating role of remnant cholesterol in the associations of Angiopoietin-like 8 with all-cause, CVD, and cancer death: the China Cardiometabolic Disease and Cancer Cohort (4C) study.

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To investigate the potential mediating effect of remnant cholesterol (RC) in the associations between angiopoietin-like 8 (ANGPTL8) and the risk of all-cause, cardiovascular disease (CVD), and cancer death. This prospective observational study included 3278 individuals from China. Binary logistic regression and mediation analyses were conducted to investigate the mediating effect of RC in the associations between ANGPTL8 and all-cause, CVD, and cancer death. During up to 5-year follow-up, a total of 265 deaths (8.08%) were documented. Both increased levels of ANGPTL8 and RC were associated with a higher risk of death for all-cause, CVD, and cancer risk. The level of RC ≥ 33 mg/dL could identify individuals at a higher risk of death independent of low-density lipoprotein cholesterol (LDL-C) levels in Chinese general populations. Furthermore, RC significantly mediated the relationship between increased ANGPTL8 levels and higher risk of all-cause, CVD, and cancer death (proportion of mediation effect: 13.10%, 9.22%, and 6.07%, respectively, all p < 0.05). Both increased circulating levels of ANGPTL8 and RC are the risk factors for all-cause, CVD, and cancer death and RC partially mediates the association between ANGPTL8 and death risk.