Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH-JAPAN study

J Clin Lipidol. May-Jun 2018;12(3):674-684.e5. doi: 10.1016/j.jacl.2018.01.014. Epub 2018 Feb 8.


Background: The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied.

Objective: We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies.

Methods: We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40-89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04-1.55 mmol/L (40-59 mg/dL) using a cohort-stratified Cox proportional hazards model.

Results: During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37-4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers.

Conclusion: We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts.

Keywords: Atherosclerotic cardiovascular disease; Cardiovascular disease; Epidemiology; High-density lipoprotein cholesterol; Mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Alcohol Drinking
  • Blood Pressure
  • Body Mass Index
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / physiopathology
  • Cholesterol, HDL / blood*
  • Cohort Studies
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Sex Distribution
  • Smoking


  • Cholesterol, HDL