Association Between High-Density Lipoprotein Cholesterol and the Risk of Cardiovascular Disorders: A Cohort Study of Healthy Adults.

High-density lipoprotein cholesterol (HDL-C) has been considered protective against cardiovascular (CV) disease, but its correlation with reduced CV risk was inconsistent. This retrospective study analyzed the relationship between HDL-C levels and CV outcomes from South Korea's National Health Insurance Service on healthy adults, focusing on conditions such as ischemic heart disease (IHD), stroke, heart failure (HF), and mortality. Cox proportional hazards regression and Kaplan-Meier curves were used for primary (CV death, IHD, stroke) and secondary (plus all-cause mortality and HF) composite endpoints. Covariates included age, sex, body mass index, blood pressure, lipid levels, glucose levels, and medication use. From 2009 to 2022, a total of 810,848 subjects were enrolled and divided into three groups based on HDL-C levels: HDL-C ≤ 40 mg/dL, 40 < HDL-C < 60 mg/dL, and HDL-C ≥ 60 mg/dL. Compared with the reference group (HDL-C, 40-60 mg/dL), individuals with HDL-C ≤ 40 mg/dL had increased risks of all-cause mortality (HR 1.05, 95% CI 1.02-1.08), CV death (HR 1.12, 95% CI 1.05-1.20), ischemic stroke (HR 1.11, 95% CI 1.07-1.15), IHD (HR 1.08, 95% CI 1.06-1.09), and HF (HR 1.09, 95% CI 1.05-1.13). HDL-C ≥ 60 mg/dL was associated with a lower risk of IHD (HR 0.95, 95% CI 0.94-0.96) but a higher risk of hemorrhagic stroke (HR 1.13, 95% CI 1.08-1.19). A U-shaped association was observed for all-cause mortality. In conclusion, higher HDL-C was associated with lower CVD risk but increased hemorrhagic stroke and all-cause mortality, suggesting the need for nuanced HDL-C interpretation.