Low mean levels and high variability of high-density lipoprotein cholesterol (HDL-C) were found to be associated with increased risks for stroke, myocardial infarction (MI) and all-cause mortality in the Korean general population, according to study results published in the Journal of the American Heart Association.

Low levels of HDL-C have been identified as a risk factor for cardiovascular events.

In this retrospective nationwide population-based cohort study, the data of 5,433,098 individuals without history of stroke or MI from the National Health Insurance System of Korea were examined.  Patients were included in the analysis if they had at least 3 health examinations between 2009 and 2013. Three methods were used to calculate the visit-to-visit variability in HDL-C levels: coefficient of variation, average real variability, and variability independent of the mean. Individuals in the lowest and highest quartiles of mean HDL-C levels and variability were considered to have low mean HDL-C and high-variability HDL-C, with sex-specific cutoffs. The study’s primary outcomes were new diagnoses of MI, stroke and all-cause mortality.

The cohort was divided into 4 groups according to mean HDL-C levels and HDL-C variability: high mean/low variability (reference group; n=3,057,031; mean age, 43.5±11.7 years; 65.4% men); high mean/high variability (n=1,024,571; mean age, 45.7±12.5 years; 67.1% men); low mean/low variability (n=1,017,774; mean age, 46.1±11.6 years; 67.1% men); and low mean/high variability (n=333,722; mean age, 48.3±12.5 years; 62.0% men). The low mean/high variability vs the other 3 groups had higher rates of diabetes mellitus (12.5%) and hypertension (28.7%) at baseline.

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During the follow-up (median, 5.1±0.6 years), there were 2,605 MIs (0.51%), 31,162 strokes (0.57%), and 50,959 deaths (0.94%) recorded. Individuals in the low mean/high variability group were found to be at a greater risk for MI (hazard ratio [HR], 1.47; 95% CI, 1.41-1.54), stroke (HR, 1.23; 95% CI, 1.18-1.28), and all-cause mortality (HR, 1.41; 95% CI, 1.36-1.45) compared with the reference group.

Adverse outcomes occurred more often in individuals with lower mean HDL-C levels or higher HDL-C variability. These 2 variables had an additive effect on the risks for MI, stroke and mortality.

Study strengths include for the inclusion of multiple possible confounders, use of a relatively healthy population, and high generalizability. Study limitations include potential selection bias, and the inability to extrapolate results to other ethnicities.

“Treatment strategies to reduce fluctuations in HDL-C might be another goal to prevent adverse health outcomes,” noted the authors.


Han BH, Han K, Yoon KH, Kim MK, Lee SH. Impact of mean and variability of high‐density lipoprotein‐cholesterol on the risk of myocardial infarction, stroke, and mortality in the general population. J Am Heart Assoc. 2020;9(7). doi:10.1161/jaha.119.015493

This article originally appeared on The Cardiology Advisor