Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase a2 activity, and 10-year cardiovascular outcomes - Prospective results from the Bruneck study

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.