High-Density Lipoprotein Cholesterol and Mortality: Too Much of a Good Thing?

Objective The objective of this study was to examine the shape of the association between high-density lipoprotein cholesterol (HDL-C) and mortality in a large general population sample. Approach and Results Adult participants (n=37059; age=57.711.9 years; 46.8% men) were recruited from general population household-based surveys (Health Survey for England and Scottish Health Survey). Individual participant data were linked with the British National Health Service Central Registry to record mortality. There were 2250 deaths from all causes during 326016 person-years of follow-up. When compared with the reference category (HDL-C=1.5-1.99 mmol/L), a U-shaped association was apparent for all-cause mortality, with elevated risk in participants with the lowest (hazard ratio=1.23; 95% confidence interval, 1.06, 1.44) and highest (1.25; 0.97, 1.62) HDL-C concentration. Associations for cardiovascular disease were linear, and elevated risk was observed in those with the lowest HDL-C concentration (1.49; 1.15, 1.94). Conclusions A U-shaped association was observed between HDL-C and mortality in a large general population sample.