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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1788.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes

Prospective Results From the Bruneck Study

Stefan Kiechl; Johann Willeit; Manuel Mayr; Brigitte Viehweider; Martin Oberhollenzer; Florian Kronenberg; Christian J. Wiedermann; Sabine Oberthaler; Qingbo Xu; Joseph L. Witztum; Sotirios Tsimikas

From the Department of Neurology (S.K., J.W.), the Division of General Internal Medicine (C.J.W., S.O., B.V., M.O.), and the Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology (F.K.), Medical University of Innsbruck, Austria; the Cardiovascular Division (Q.X., M.M.), King’s College London, University of London, UK; and the Department of Medicine (J.L.W., S.T.), University of California San Diego, La Jolla.

Correspondence to Sotirios Tsimikas, Vascular Medicine Program, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA 92093-0682. E-mail stsimikas{at}ucsd.edu

Background— Oxidized phospholipids (OxPL) circulate on apolipoprotein B-100 particles (OxPL/apoB), and primarily on Lp(a) lipoprotein (a) [Lp(a)]. The relationship of OxPL/apoB levels to future cardiovascular events is not known.

Methods and Results— The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women recruited in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 subjects in 1995 and incident cardiovascular disease (CVD), defined as cardiovascular death, myocardial infarction, stroke, and transient ischemic attack, was assessed from 1995 to 2005. During the follow-up period, 82 subjects developed CVD. In multivariable analysis, which included traditional risk factors, high sensitivity C-reactive protein (hsCRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, subjects in the highest tertile of OxPL/apoB had a significantly higher risk of cardiovascular events than those in the lowest tertile (hazard ratio[95% CI] 2.4[1.3 to 4.3], P=0.004). The strength of the association between OxPL/apoB and CVD risk was amplified with increasing Lp-PLA2 activity (P=0.018 for interaction). Moreover, OxPL/apoB levels predicted future cardiovascular events beyond the information provided by the Framingham Risk Score (FRS). The effects of OxPL/apoB and Lp(a) were not independent of each other but they were independent of all other measured risk factors.

Conclusions— This study demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently of traditional risk factors, hsCRP, and FRS. Increasing Lp-PLA2 activity further amplifies the risk of CVD mediated by OxPL/apoB.

Oxidized phospholipids (OxPL) detected by monoclonal antibody E06 (OxPL/apoB), lipoprotein(a), and Lp-PLA2 activity were measured in the Bruneck Study, where 82 of 765 subjects developed cardiovascular events over 10 years. OxPL/apoB and Lp(a) predicted 10-year cardiovascular events independently of traditional risk factors, hsCRP, and the Framingham risk score. Increasing Lp-PLA2 activity further amplified the risk mediated by OxPL/apoB and Lp(a).

Key Words: lipoproteins • oxidation • atherosclerosis • lipoprotein (a) • oxidized phospholipids • lipoprotein-associated phospholipase A2

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