The beneficial effects of raising high-density lipoprotein cholesterol depends upon achieved levels of low-density lipoprotein cholesterol during statin therapy: Implications for coronary atheroma progression and cardiovascular events

Eur J Prev Cardiol. 2016 Mar;23(5):474-85. doi: 10.1177/2047487315572920. Epub 2015 Feb 17.

Abstract

Aims: Controversy exists regarding benefits of raising HDL-C in statin-treated coronary artery disease (CAD) patients. We assessed the anti-atherosclerotic efficacy of raising HDL-C in statin-treated individuals with CAD across a range of achieved LDL-C, including lower (<70 mg/dL) versus higher (≥70 mg/dL) levels.

Methods and results: In seven prospective randomized trials utilizing serial coronary intravascular ultrasound, 3469 statin-treated CAD patients were stratified according to achieved LDL-C (< vs ≥70 mg/dL) and changes in HDL-C (≥ vs < median), as well as across a broader spectrum of changes in HDL-C and achieved LDL-C levels. Changes in coronary percent atheroma volume and MACE (cardiovascular death, non-fatal MI, stroke, coronary revascularization, hospitalization for unstable angina) were evaluated across these groups.

Results: Overall, median change in HDL-C was +6.03%, and mean achieved LDL-C in the lower and higher LDL-C groups were 55.1 ± 11 and 97.4 ± 22 mg/dL, respectively. Following multivariable adjustment, in patients with achieved LDL-C < 70 mg/dL, greater HDL-C-raising did not associate with disease progression/regression. In those with achieved LDL-C ≥ 70 mg/dL, greater HDL-C-raising associated with less disease progression (OR 0.80 (95% CI 0.67, 0.97)) and MACE (HR 0.78 (95% CI 0.64, 0.96)). Greater increases in HDL-C (up to 25% from baseline) across the continuous range of on-treatment LDL-C levels associated with less disease progression )OR 0.90 (95% CI 0.83, 0.98)) and lower MACE (HR 0.87 (95% CI 0.77, 0.998)).

Conclusions: Increasing HDL-C via a broad spectrum of mechanisms appears beneficial in statin-treated CAD patients, but is likely of greater benefit in patients with achieved LDL-C levels ≥70 mg/dL.

Keywords: HDL-C; IVUS; LDL-C; coronary artery disease; statins.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Chi-Square Distribution
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / mortality
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Plaque, Atherosclerotic
  • Proportional Hazards Models
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Interventional
  • Up-Regulation

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors