High-density lipoprotein cholesterol and cardiovascular mortality: a prospective cohort study among 15.8 million adults.

Aims: We aimed to investigate whether the associations between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) mortality and the optimal range differ by age and CVD subtypes.

Methods And Results: Korean adults (n = 15 859 501) with no CVD/cancer who received routine health examinations during 2009-2010 were followed until 2018 for CVD mortality. During a mean 8.8 years of follow-up, 108 123 individuals died from CVD. U-curve associations were found between HDL-C and CVD mortality, regardless of sex, age, and CVD subtype. The optimal range was 50-79 mg/dL (1.29-2.06 mmol/L), while it was 40-69 (1.03-1.80), 50-79 (1.29-2.06), and 60-89 (1.55-2.32) mg/dL (mmol/L) in adults aged <45 years, 45-64 years, and 65-99 years, respectively. Assuming linear associations <60 mg/dL, the multivariable-adjusted hazard ratios (HRs) per 39 mg/dL (1 mmol/L) higher level were 0.58 (95% confidence interval = 0.56-0.60), and they were 0.61 (0.52-0.72), 0.58 (0.54-0.62), and 0.59 (0.56-0.61) in individuals aged 18-44, 45-64, and 65-99 years, respectively [Pinteraction (age) = 0.845]. Assuming linear associations in the 60-150 mg/dL range, HDL-C was positively associated with CVD mortality (HR = 1.09, 1.04-1.14). The strongest association was for sudden cardiac death (SCD) (HR = 1.37), followed by heart failure (HF) (HR = 1.20) and intracerebral haemorrhage (ICH) (HR = 1.13). The HRs were 1.47 (1.23-1.76), 1.17 (1.08-1.28), and 1.03 (0.97-1.08) in individuals aged 18-44, 45-64, and 65-99 years, respectively [Pinteraction (age) < 0.001].

Conclusion: Both low and high levels of HDL-C were associated with increased mortality from CVD in the general population, especially SCD, HF, and ICH. High HDL-C levels are not necessarily a sign of good cardiovascular health, especially in younger adults.