High-Density Lipoprotein Cholesterol and the Risk of Myocardial Infarction, Stroke, and Cause-Specific Mortality: a Nationwide Cohort Study in Korea

OBJECTIVE: We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) level and the risk of myocardial infarction (MI), stroke, and cause-specific mortality. METHODS: Using the Korean National Health Insurance Service-National Sample Cohort, we identified 343,687 subjects (men, 176,243; women, 167,444) aged ≥20 years who underwent health examinations between 2009 and 2012. HDL-C levels were categorized based on the concentration with 10 mg/dL intervals, starting from levels <30 mg/dL, with levels ≥90 mg/dL considered the highest. The endpoints of the study were newly-diagnosed MI, stroke, or mortality. We used the Cox proportional hazards model with restricted cubic splines. RESULTS: During a median follow-up of 6.0 years, the number of cases of death, MI, and stroke were 6,617, 4,064, and 3,435 in men and 3,677, 2,804, and 2,891 in women, respectively. The risk of all-cause mortality, cancer mortality, other mortality, and stroke was the lowest at HDL-C concentrations of 57-76 mg/dL in the spline curves; inverse associations with increased risk were observed at the lower HDL-C levels. In contrast, the lowest risk of cardiovascular mortality and MI was observed at the extreme high end. In men, there was a significant inverse and graded increase in hazard ratios of all outcomes in the lower HDL-C categories compared to the reference group (50-59 mg/dL). In the higher HDL-C categories, no significant increase in outcomes was observed. Women showed similar trends. CONCLUSION: The risk of mortality, MI, and stroke was high at low HDL-C levels in the Korean general population. However, extremely high HDL-C levels were not associated with an increased risk of mortality, MI, and stroke.