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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1177.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women

The EPIC-NORFOLK Study

Ziad Mallat; Joelle Benessiano; Tabassome Simon; Stéphane Ederhy; Carla Sebella-Arguelles; Ariel Cohen; Virginie Huart; Nicholas J. Wareham; Robert Luben; Kay-Tee Khaw; Alain Tedgui; S. Matthijs Boekholdt

From INSERM (Z.M., A.T.), U689, Centre de Recherche Cardiovasculaire Lariboisière, Paris, France; Department of Pharmacology (T.S.), AP-HP, Hôpital Saint-Antoine-URCEST, and Université Pierre et Marie Curie (UPMC), Paris, France; Centre d’Investigation Clinique et Centre de Ressources Biologiques (J.B., C.S.-A., V.H.), AP-HP, Hôpital Bichat, Paris, France; Department of Cardiology (S.E.), UPMC and Hôpital Saint-Antoine, Paris, France; Medical Research Council (N.J.W.), Epidemiology Unit, Cambridge, UK; Department of Public Health and Primary Care (R.L., K.-T.K.), University of Cambridge, Cambridge, UK; Departments of Cardiology and Vascular Medicine (M.B.), Academic Medical Center, Amsterdam, The Netherlands.

Correspondence to Ziad Mallat, MD, PhD, Inserm U689, Hôpital Lariboisière, 75010, Paris, France. E-mail ziad.mallat{at}larib.inserm.fr

Objective— To assess the association between secretory phospholipase A2 (sPLA2) activity, which encompasses several types of sPLA2, and cardiovascular disease (CAD) in healthy individuals.

Methods and Results— We investigated this association in a nested case-control study among the 25 663 participants in EPIC-Norfolk cohort. Cases (n=991) were subjects in whom CAD developed during the 6 years of mean follow-up. Controls (n=1806) matched by age, sex, and enrollment time remained free of any CAD during follow-up. The risk of incident CAD was associated with increasing quartiles of sPLA2 activity (P<0.001). After adjustment for risk factors, C-reactive protein and sPLA2 type IIA concentration, the odds ratios of incident CAD in the second, third, and fourth quartiles of sPLA2 activity were 1.41, 1.33, and 1.56 (P=0.003), compared with the lowest quartile. sPLA2 activity and CRP were poorly correlated (r=0.15), and their combined values were more informative for incident risk of CAD than either biomarker alone. Subjects in the highest quartiles of sPLA2 activity and CRP had an adjusted odds ratio of 2.89 (95% confidence interval, 1.78 to 4.68; P<0.001) for CAD compared with those with the lowest quartiles of both markers.

Conclusions— Measurement of serum sPLA2 activity provides additive prognostic value to traditional risk factors and CRP levels, and identifies a subgroup of individuals at high risk for incident CAD. Measurement of sPLA2 type II concentration had little added prognostic utility.

In a nested case-control study among 25 663 healthy participants of EPIC-Norfolk cohort, the risk of incident coronary artery disease was associated with increasing quartiles of serum sPLA2 activity. sPLA2 activity and CRP levels provided better prediction of risk than either biomarker alone. The odds ratio of risk was 2.89 (95% CI, 1.78 to 4.68; P<0.001) in the highest quartiles of sPLA2 activity and CRP, compared with those in the lowest quartiles of both markers.

Key Words: biomarker • coronary artery disease • phospholipase A2 • prevention • risk factors

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