Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis

Circulation. 2013 Oct 1;128(14):1504-12. doi: 10.1161/CIRCULATIONAHA.113.002670. Epub 2013 Aug 21.


Background: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk.

Methods and results: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).

Conclusions: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Keywords: apolipoproteins; cardiovascular diseases; high-density lipoprotein cholesterol; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angina, Unstable / epidemiology
  • Angina, Unstable / prevention & control
  • Apolipoprotein A-I / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic / statistics & numerical data
  • Follow-Up Studies
  • Heart Failure / epidemiology
  • Heart Failure / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Peripheral Arterial Disease / epidemiology
  • Peripheral Arterial Disease / prevention & control
  • Proportional Hazards Models
  • Risk Factors
  • Risk Reduction Behavior
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Treatment Outcome
  • Triglycerides / blood


  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Triglycerides