Lower levels of high-density lipoprotein cholesterol are associated with increased cardiovascular events in patients with acute coronary syndrome


      • This study evaluated HDL-C and cardiovascular (CV) risk in acute coronary syndrome.
      • Lower HDL-C is associated with higher incidence of CV events.
      • Predictive ability is independent of intensive or conventional lipid-lowering therapy.
      • These trends remained after adjustment for baseline values and lipid profiles.
      • Lower BMI, diabetes mellitus, and higher hs-CRP at baseline independently predicted CV events.


      Background and aims

      This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events.


      The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. The entire cohort was divided into three groups according to tertiles of HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, HDL-C >43, <53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups.


      The primary endpoint event occurred in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively, and its incidence was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19–1.9; p = 0.001). Irrespective of the treatment regimen, Group 1 had significantly higher rates of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12–2.22; p = 0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05–1.98; p = 0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Multivariate analysis revealed that lower body mass index, prevalence of diabetes mellitus, higher levels of high-sensitivity C reactive protein at baseline, and lower levels of HDL-C at 3-month follow-up were independent predictors of the incidence of primary endpoint.


      Lower levels of HDL-C at 3-month follow-up are independently associated with higher incidence of cardiovascular events in ACS patients receiving contemporary lipid-lowering therapy.

      Graphical abstract


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