Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial

Am Heart J. 2020 Mar:221:60-66. doi: 10.1016/j.ahj.2019.12.003. Epub 2019 Dec 16.

Abstract

Background: High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS).

Methods: The dal-Outcomes trial compared the CETP inhibitor dalcetrapib with placebo in patients with recent ACS. In a nested case-cohort analysis, total, large, medium, and small HDLPs were measured by nuclear magnetic resonance spectroscopy at baseline (4-12 weeks after ACS) in 476 cases with MACE and 902 controls. Hazard ratios (HRs; case-control) for 1-SD increment of HDLP or HDL-C at baseline were calculated with and without adjustment for demographic, clinical, laboratory, and treatment variables. Similarly, HRs for MACE were calculated for changes in HDLP or HDL-C from baseline to month 3 of assigned treatment.

Results: Over median follow-up of 28 months, the risk of MACE was not associated with baseline HDLP (adjusted HR = 0.98, 95% CI = 0.84-1.15, P = .81), any HDLP subclass, or HDL-C. Dalcetrapib increased HDL-C and total, medium, and large HDLP and decreased small HDLP but had no effect on MACE compared with placebo. There were no association of risk of MACE with change in HDLP or HDL-C and no interaction with assigned study treatment.

Conclusions: Neither baseline HDLP nor the change in HDLP on treatment with dalcetrapib or placebo was associated with risk of MACE after ACS.

Trial registration: ClinicalTrials.gov NCT00658515.

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / drug therapy
  • Aged
  • Amides
  • Angina, Unstable / epidemiology*
  • Anticholesteremic Agents / therapeutic use
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Coronary Disease / mortality*
  • Esters
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Lipoproteins, HDL / blood*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Stroke / epidemiology*
  • Sulfhydryl Compounds / therapeutic use

Substances

  • Amides
  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Esters
  • Lipoproteins, HDL
  • Sulfhydryl Compounds
  • dalcetrapib

Associated data

  • ClinicalTrials.gov/NCT00658515