Oxidation-specific biomarkers, prospective 15-year cardiovascular and stroke outcomes, and net reclassification of cardiovascular events.

Abstract

OBJECTIVES:

This study sought to assess the long-term predictive value and net reclassification for risk of cardiovascular disease (CVD) of biomarkers reflecting oxidation-specific epitopes (OSEs).

BACKGROUND:

OSEs are immunogenic, proinflammatory, and proatherogenic. The long-term predictive value and net reclassification of OSEs for risk of CVD events are not known.

METHODS:

Oxidized phospholipids on apolipoprotein B-100 (OxPL/apoB) and immunoglobulin (Ig)-G (IgG) and IgM autoantibodies to malondialdehyde-modified, low-density lipoprotein (MDA-LDL) and copper-oxidized LDL (Cu-OxLDL) were measured in 765 subjects in 1995 and 656 subjects in 2000 in the Bruneck study, representing 45- to 84-year-old men and women from the general community.

RESULTS:

Over 15 years of follow-up, 138 subjects reached the primary endpoint of incident CVD (ischemic stroke, myocardial infarction, new-onset unstable angina, acute coronary interventions, and vascular death). In a multivariable Cox model, the highest tertile of OxPL/apoB was associated with higher risk of CVD (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.5 to 3.7) and stroke (HR: 3.6; 95% CI: 1.8 to 7.4) compared with the lowest tertile. IgG Cu-OxLDLs were associated with higher risk of CVD, whereas IgM MDA-LDLs were associated with lower risk. Using OxPL/apoB, IgG Cu-OxLDL, and IgM MDA-LDL variables, the area under the curve (AUC) for CVD risk prediction increased from 0.664 (95% CI: 0.629 to 0.697) to 0.705 (95% CI: 0.672 to 0.737) (p = 0.048). The net reclassification index (NRI) was 0.163 (p = 0.0044) and 0.332 (p < 0.0001) in all subjects (n = 765) and in subjects with intermediate risk (n = 305), respectively. Of 627 subjects who remained free of CVD, 108 were correctly reclassified to a lower risk category, and 83 were reclassified to a higher category (categories: 15-year risk <15%, 15% to 30%, >30%).

CONCLUSIONS:

OSE biomarkers predict 15-year CVD and stroke outcomes and provide potential clinical utility by reclassifying a significant proportion of individuals into higher or lower risk categories after traditional risk assessment.

• Authors: Sotirios Tsimikas, Peter Willeit, Johann Willeit, Peter Santer, Manuel Mayr, Qingbo Xu, Agnes Mayr, Joseph L Witztum, Stefan Kiechl
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 60 Issue 21 Pg. 2218-29 (Nov 20 2012) ISSN: 1558-3597 [Electronic] United States
• PMID: 23122790 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Epitopes
• Phospholipids

Topics

• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Cardiovascular Diseases (blood, classification, epidemiology)
• Epitopes
• Female
• Follow-Up Studies
• Forecasting (methods)
• Humans
• Incidence
• Italy (epidemiology)
• Male
• Middle Aged
• Oxidation-Reduction
• Phospholipids (blood)
• Prospective Studies
• Stroke (blood, classification, epidemiology)
• Survival Rate (trends)