Elsevier

Mayo Clinic Proceedings

Volume 82, Issue 2, February 2007, Pages 159-165
Mayo Clinic Proceedings

ORIGINAL ARTICLE
Association Between Lipoprotein-Associated Phospholipase A2 and Cardiovascular Disease: A Systematic Review

https://doi.org/10.4065/82.2.159Get rights and content

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inception through 2006), conference proceedings, and reference sections of obtained articles and contacted experts for unpublished studies.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 random-effects 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.

Section snippets

Selection Criteria

Eligible studies were case-control studies alone or nested in cohort studies and cohort studies with at least 1 year of follow-up that measured CVD risk in terms of blood levels of Lp-PLA2 and were published in English. We excluded studies that reported on the association between Lp-PLA2 and stable angina alone and studies with fewer than 50 participants.

Literature Search

We searched MEDLINE (January 1, 1985, through September 30, 2006), the Cochrane library (from inception through September 2006), conference

RESULTS

Computerized and hand searches identified 119 articles and abstracts. Of these, we retrieved 28 for closer evaluation and selected 12 full-length articles and 2 abstracts for inclusion (Figure 1). One potentially eligible study was excluded because Lp-PLA2 was measured at baseline and 30 days after, reporting 2 different risk estimates.18 After an exhaustive search for unpublished data, none of the investigators in the field who were contacted were aware of unpublished studies. Table 1 gives

DISCUSSION

The results of this systematic review support an association between elevated blood levels of Lp-PLA2 and increasedCVD risk. The measure of association chosen (either hazard ratio or relative risk vs odds ratio) and the methods used to report results (extreme percentiles vs ≥1-SD change from mean) explained the inconsistency in results across studies. Among the studies included in the meta-analysis, 2 did not show a significant association between Lp-PLA2 and CVD. The negative results of the

CONCLUSION

Lipoprotein-associated phospholipase A2 is significantly associated with CVD, with only limited influence of conventional CVD risk factors on this relationship. In addition, Lp-PLA2 may be useful in CVD risk stratification and may represent a therapeutic target for cardiovascular risk reduction.

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    Dr Somers is supported by National Institutes of Health grants HL65176, HL61560, HL 70302, and M01-RR00585. Dr Kullo is supported by National Institutes of Health grant HL-813301. Dr Lopez-Jimenez is a recipient of a Clinical Scientist Development Award from the American Heart Association.

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