This study aimed to investigate the association of high-density lipoprotein cholesterol (HDL-C) levels with cardiovascular diseases (CVDs) and all-cause mortality and to determine differences based on the presence or absence of a history of CVDs. This retrospective cohort study included 343,321 adults aged ≥ 40 years whose survey data were recorded in the Korean National Health Insurance Service database from 2009 to 2010. HDL-C levels were divided into five groups. The association among HDL-C levels, CVDs, and all-cause mortality was examined using multivariate Cox proportional hazards regression models. During a mean follow-up period of 9.5 ± 2.0 years, CVDs, all-cause mortality, and composite outcomes occurred in 8.3%, 5.9%, and 13.2% of the study population, respectively. HDL-C levels were inversely associated with CVDs and composite outcomes, with a U-shaped association between HDL-C levels and all-cause mortality. Compared with normal HDL-C levels, very low HDL-C levels and very high HDL-C levels were associated with a higher risk of all-cause mortality. Individuals without preexisting CVDs showed similar patterns. Very low HDL-C and low HDL-C levels in individuals with preexisting CVDs were associated with a higher risk of outcomes. Our results suggest that very high HDL-C levels are associated with a decreased risk of CVDs and an increased risk of all-cause mortality. These associations varied according to preexisting CVDs status, sex, and age, challenging the notion that a higher HDL-C level is universally beneficial.
Huh et al. (2026) studied this question.