Association between lipoprotein-associated phospholipase A₂ and cardiovascular disease: A systematic review

OBJECTIVE: To estimate the association between plasma lipoprotein- associated phospholipase A₂ (Lp-PLA₂) levels and cardiovascular disease (CVD). METHODS: We searched MEDLINE (January 1, 1985, through September 30, 2006), the Cochrane library (from inception through 2006), conference proceedings, and reference sections of obtained articles and contacted experts for unpublished studies. Eligible studies were cohorts with 1 year or more of follow-up or case-control designs that provided risk estimates for CVD according to blood levels of Lp-PLA₂ that were unadjusted or adjusted for conventional CVD risk factors. We used randomeffects meta-analysis to estimate the association between Lp-PLA₂ and CVD risk and conducted preplanned subgroup analyses to identify risk-subgroup interactions that could explain between-study differences. RESULTS: We found 14 eligible studies (N=20,549 patients) that reported either Lp-PLA₂ plasma activity (n=5) or an immunoassay that measured the plasma concentration (n=9). The meta-analytic estimate from the unadjusted odds ratio for the association between elevated Lp-PLA₂ levels and CVD risk was 1.51 (95% confidence interval, 1.30-1.75) and from the odds ratio adjusted for conventional CVD risk factors was 1.60 (95% confidence interval, 1.36-1.89). Differences in study methods explained differences in results across studies. CONCLUSIONS: Lipoprotein-associated phospholipase A₂ is significantly associated with CVD. The risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. Measurement of Lp-PLA₂ may be useful in CVD risk stratification. In addition, Lp-PLA₂ may represent a potential therapeutic target for CVD risk reduction.