Relationship of oxidized phospholipids on apolipoprotein B-100 to cardiovascular outcomes in patients treated with intensive versus moderate atorvastatin therapy: the TNT trial

J Am Coll Cardiol. 2015 Apr 7;65(13):1286-1295. doi: 10.1016/j.jacc.2015.01.050.

Abstract

Background: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown.

Objectives: This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD.

Methods: In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal/nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE.

Results: Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (hazard ratio: 1.69; 95% confidence interval [CI]: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index, among others, and treatment assignment. In the atorvastatin 10-mg group, tertile 3 was associated with a higher risk of MACE compared to the first tertile (HR: 2.08; 95% CI: 1.20 to 3.61; p = 0.01) but this was not significant in the atorvastatin 80-mg group (HR: 1.40; 95% CI: 0.80 to 2.46; p = 0.24).

Conclusions: Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).

Keywords: atherosclerosis; biomarker; coronary heart disease; inflammatory; oxidation-specific epitope.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein B-100 / blood*
  • Atorvastatin
  • Biomarkers / blood
  • Cardiovascular Diseases / etiology*
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Phospholipids / blood*
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Risk Factors

Substances

  • Apolipoprotein B-100
  • Biomarkers
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Phospholipids
  • Pyrroles
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00327691