HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies

Objective The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose–response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population.Methods PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose–response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio.Results Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response pattern, with the lowest risk observed at HDL-C levels of 54–58 mg/dL, 68–71 mg/dL and 64–68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality.Conclusions In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.