Impact of mean and variability of high-density lipoprotein-cholesterol on the risk of myocardial infarction, stroke, and mortality in the general population

BACKGROUND: A low level of high-density lipoprotein-cholesterol (HDL-C) is a well-known risk factor for cardiovascular events. Recent studies have also suggested that HDL-C variability has a predictive role in patients with coronary artery disease. We investigated the combined effect of the mean and variability of HDL-C on the risk of myocardial infarction (MI), stroke, and mortality in the general population. METHODS AND RESULTS: We selected 5 433 098 subjects in the Korean National Health Insurance System cohort who had no history of MI or stroke and who underwent ≥3 health examinations between 2009 and 2013. Visit-to-visit HDL-C variability was calculated using the coefficient of variation, variability independent of the mean and average real variability. The low-mean and high-variability groups were defined as the lowest and highest quartiles of HDL-C mean and variability, respectively. There were 27 605 cases of MI, 31 162 cases of stroke, and 50 959 deaths during the median follow-up of 5.1±0.6 years. A lower mean or higher variability (coefficient of variation) of HDL-C was associated with a higher risk of adverse outcomes, and the 2 measures had an additive effect. In the multivariable-adjusted model, the hazard ratios (95% CIs) of the low-mean/ high-variability group compared with the high-mean/low-variability group were 1.47 (1.41–1.54) for MI, 1.23 (1.18–1.28) for stroke, and 1.41 (1.36–1.45) for all-cause mortality. Results were consistent when variability was modeled using variability independent of the mean or average real variability, and in various sensitivity and subgroup analyses. CONCLUSIONS: Low mean and high variability of HDL-C is associated with an increased risk of MI, stroke, and mortality.