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

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).

• Authors: Young Sup Byun, Jun-Hee Lee, Benoit J Arsenault, Xiaohong Yang, Weihang Bao, David DeMicco, Rachel Laskey, Joseph L Witztum, Sotirios Tsimikas, TNT Trial Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 65 Issue 13 Pg. 1286-1295 (Apr 07 2015) ISSN: 1558-3597 [Electronic] United States
• PMID: 25835440 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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