The association between lipoprotein-associated phospholipase A2 and cardiovascular disease and total mortality in vascular medicine patients

Introduction: In some community-based studies, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been shown to be independently predictive of future fatal and nonfatal cardiovascular disease (CVD) events. We tested the hypothesis that Lp-PLA(2) is independently predictive of mortality in high-risk patients from a vascular laboratory. Methods: Between 1990 and 1994, patients seen in the previous 10 years for noninvasive lower extremity arterial testing were invited to return for a vascular examination of the lower extremities. By medical record review, we identified 2265 eligible patients; of these, 508 returned for interviews, blood collection, and arterial examination and represent those who had survived, could be located, and were willing to participate. The 508 subjects were followed up for an average of 6.7 years until the end of the study period on December 31, 2001. Vital status was ascertained by multiple searches of the Social Security Death Index. The primary outcomes for this study were time to any, CVD, and coronary heart disease (CHD) mortality. Results. The mean age was 68.2 years, 88% were men, 87% were non-Hispanic white, 39.1% were diagnosed with peripheral arterial disease only, 9.2% with other CVD only, and 28.5% with both peripheral arterial disease and other CVD. During the entire follow-up period, 299 (59.7%) patients died, 167 from CVD, of which 88 deaths were due to coronary heart disease. With adjustment for CVD risk factors and baseline peripheral arterial disease and other CVD, an increment of one standard deviation in Lp-PLA(2) activity was associated with a 40% higher risk for CHD mortality at 5 years of follow-up (P =.04). Additional adjustment for triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol reduced this association to nonsignificance (hazard risk, 1.12). Conclusion: In a vascular laboratory patient population, higher levels of LpPLA2 mass and activity were not significantly associated with total, CVD, or CHD mortality at 5 years of follow-up and after adjustment for traditional CVD risk factors and the presence of PAD and other CVD at baseline. An apparent elevated risk of CHD death associated with elevated Lp-PLA2 was largely explained by associated elevations in lipids and lipoproteins.