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CLINICAL STUDY

A prospective evaluation of lipoprotein-associated phospholipase A₂ levels and the risk of future cardiovascular events in women

Gavin J. Blake, MB, MSc, MRCPI^* , Nisha Dada, BS^||, Jonathan C. Fox, MD, FACC^¶, JoAnn E. Manson, MD, DrPH and Paul M. Ridker, MD, MPH, FACC^*,*

^* Center for Cardiovascular Disease Prevention, Boston, Massachusetts, USA
Division of Preventive Medicine, Boston, Massachusetts, USA
Division of Cardiovascular Disease, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Leducq Center for Cardiovascular Research, Harvard Medical School, Boston, Massachusetts, USA
^|| diaDexus, Inc., Santa Clara, California, USA
^¶ GlaxoSmithKlein, Philadelphia, Pennsylvania, USA

Manuscript received April 13, 2001; revised manuscript received July 10, 2001, accepted July 23, 2001.

^* Reprint requests and correspondence: Dr. Paul M. Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215 USA
pridker{at}partners.org

OBJECTIVES

We sought to determine prospectively whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂) was a predictor of future cardiovascular risk in women.

BACKGROUND

Inflammatory markers may help predict cardiovascular risk. Lp-PLA₂ levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men.

METHODS

We conducted a prospective, nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease, non-fatal myocardial infarction, and stroke associated with baseline levels of Lp-PLA₂ over a mean follow-up of three years.

RESULTS

In univariate analysis, mean levels of Lp-PLA₂ correlated strongly with low-density lipoprotein cholesterol (r = 0.51; p = 0.0001), were lower among women currently using hormone replacement therapy (mean 0.98 mg/l vs. 1.23 mg/l; p = 0.0001) and were significantly higher at baseline among cases (n = 123) than controls (n = 123) (mean 1.20 mg/l vs. 1.05 mg/l; p = 0.016). However, the predictive value of Lp-PLA₂ was markedly attenuated after adjustment for these and other cardiovascular risk factors. Specifically, the multivariate relative risks of future cardiovascular events for women in the lowest (referent) to highest quartiles of Lp-PLA₂ were 1.00, 0.75, 0.64 and 1.17, respectively (all p values non-significant). In contrast, the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein (another marker of low-grade inflammation) were 1.00, 1.78, 2.02 and 4.66, respectively (p-value for trend = 0.002). Inclusion of Lp-PLA₂ levels did not significantly attenuate this latter observation.

CONCLUSIONS

In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA₂ is not a strong predictor of future cardiovascular risk among unselected women.

Abbreviations and Acronyms   CI = confidence interval   CHD = coronary heart disease   CRP = C-reactive protein   HDL = high-density lipoprotein   LDL = low-density lipoprotein   Lp-PLA2 = lipoprotein-associated phospholipase A2   MI = myocardial infarction   WHS = Women’s Health Study

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