Associations of high-density lipoprotein cholesterol concentration and particle count with mortality: a prospective study of 50,000 men and 100,000 women

Background and objectives: More research is needed on how high-density lipoprotein (HDL) cholesterol concentration and particle count relate to mortality. This analysis tested whether HDL concentration has non-linear associations with all-cause mortality, whether cardiovascular disease (CVD) deaths, cancer deaths, or other deaths drove those associations, and whether small, medium, or large HDL particle count was associated with mortality.

Methods: The sample included 47,123 men and 97,589 women from the Mexico City Prospective Study. Models were adjusted for confounders and competing risks. There were 11,264 deaths in men and 15,486 deaths in women.

Results: In men, HDL concentration showed a J-shaped association with all-cause mortality driven by other deaths. Compared with the >40th-60th percentile group, the hazard ratio (95% confidence interval) for other mortality was 1.27 (1.11, 1.44) in the >95th-99th percentile group and 1.82 (1.45, 2.28) in the >99th-100th percentile group. In women, the association was U-shaped, driven by CVD deaths at lower concentrations and other deaths at higher concentrations: the hazard ratio for CVD mortality was 1.23 (1.05, 1.43) in the two lowest percentile groups, and the hazard ratio for other mortality was 1.33 (1.18, 1.50) in the two highest percentile groups. Small HDL particle count was associated with reduced risk of all-cause, CVD, and other mortality in both men and women; for example, compared with the bottom quartile, the hazard ratio for all-cause mortality was 0.79 (0.73, 0.86) in the top quartile in men and 0.77 (0.72, 0.82) in the top quartile in women.

Conclusions: HDL concentration shows a J-shaped association with mortality in men and a U-shaped association in women. More research is required to confirm the novel finding that small HDL particle count reduces the risk of all-cause, CVD, and other mortality in men and women.