Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER

Atherosclerosis. 2018 Jul:274:139-145. doi: 10.1016/j.atherosclerosis.2018.04.036. Epub 2018 May 5.


Background and aims: We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia.

Methods: This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined.

Results: The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy.

Conclusions: Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach.

Keywords: Acute coronary syndrome; Ezetimibe; Lipid-lowering; Pitavastatin; Sitosterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / mortality
  • Aged
  • Biomarkers / blood
  • Cholesterol, LDL / blood
  • Dyslipidemias / blood*
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy
  • Dyslipidemias / mortality
  • Ezetimibe / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Japan
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Quinolines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sitosterols / blood*
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • Sitosterols
  • gamma-sitosterol
  • Ezetimibe
  • pitavastatin