Oxidation-Specific Biomarkers, Prospective 15-Year Cardiovascular and Stroke Outcomes, and Net Reclassification of Cardiovascular Events

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• 作者：Sotirios Tsimikas ; MD^? ; ^{stsimikas@ucsd.edu} ; Peter Willeit ; MD ; MPhil^&dagger ; ; ^&Dagger ; ; Johann Willeit ; MD^&dagger ; ; Peter Santer ; MD^§ ; ; Manuel Mayr ; MD ; PhD^¡Î ; Qingbo Xu ; PhD^¡Î ; Agnes Mayr ; MD^§ ; ; Joseph L. Witztum ; MD^? ; Stefan Kiechl ; MD^&dagger ; ; ^{Stefan.Kiechl@i-med.ac.at}
• 关键词：atherosclerosis ; autoantibodies ; lipoproteins ; oxidation ; oxidation-specific epitopes ; oxidized phospholipids
• 刊名：Journal of the American College of Cardiology
• 出版年：2012
• 出版时间：20-27 November, 2012
• 年：2012
• 卷：60
• 期：21
• 页码：2218-2229
• 全文大小：1815 K

文摘

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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.