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CLINICAL RESEARCH: ACUTE CORONARY SYNDROMES

Circulating Secretory Phospholipase A2 Activity Predicts Recurrent Events in Patients With Severe Acute Coronary Syndromes

Ziad Mallat, MD, PhD^_*,_*, Ph. Gabriel Steg, MD, PhD, Joëlle Benessiano, MD, PhD, Marie-Laure Tanguy, PhD, Keith A. Fox, FESC^||, Jean-Philippe Collet, MD, PhD^¶, Omar H. Dabbous, MD, MPH^#, Patrick Henry, MD^_**, Kathryn F. Carruthers, MPhil^||, Anne Dauphin, MSc, Carla Sibella Arguelles, MSc, Joëlle Masliah, PhD, Bénédicte Hugel, PhD, Gilles Montalescot, MD, PhD^¶, Jean-Marie Freyssinet, PhD, Bernard Asselain, PhD and Alain Tedgui, PhD^_*

^_* Institut National de la Santé et la Recherche Médicale, (INSERM U541), Institut Fédératif de Recherche (IRF) "Circulation," Paris, France
Service de Cardiologie, Hôpital Bichat, Paris, France
Centre d’Investigation Clinique, CIC 07, Hôpital Bichat, Paris, France
Département de Biostatistiques, Institut Curie, Paris, France
^¶ Service de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France
^_** Service de Cardiologie, Hôpital Lariboisière, Paris, France
Service de Biochimie, Hôpital St. Antoine, Paris, France
Institut d’Hématologie et d’Immunologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, and INSERM U143, Le Kremlin-Bicêtre, France
^|| Cardiovascular Research Unit, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
^# University of Massachusetts Medical School, Worcester, Massachusetts

Manuscript received March 30, 2005; revised manuscript received May 25, 2005, accepted June 6, 2005.

^_* Reprint requests and correspondence: Dr. Ziad Mallat, Inserm U541, Hôpital Lariboisière, 75010 Paris, France. (Email: mallat{at}larib.inserm.fr).

OBJECTIVES: The purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS).

BACKGROUND: The plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown.

METHODS: Secretory phospholipase A2 antigen levels and activity were measured in plasma samples of 446 patients with ACS, obtained at the time of enrollment.

RESULTS: Baseline sPLA2 activity was associated with the risk of death and myocardial infarction (MI). The unadjusted rate of death and MI increased in a stepwise fashion with increasing tertiles of sPLA2 activity (p < 0.0001). The association remained significant in the subgroup of patients who had MI with ST-segment elevation (p = 0.014) and the subgroup of patients who had unstable angina or non–ST-segment elevation MI (p < 0.002). After adjustment for clinical and biological variables, the hazard ratios for the combined end point of death or MI in the third tertile of sPLA2 compared with the first and second tertiles was 3.08 (95% confidence interval, 1.37 to 6.91, p = 0.006).

CONCLUSIONS: A single measurement of plasma sPLA2 activity at the time of enrollment provides strong independent information to predict recurrent events in patients with ACS.

Abbreviations and Acronyms   ACS = acute coronary syndromes   CAD = coronary artery disease   CRP = C-reactive protein   GRACE = Global Registry of Acute Coronary Events   hsCRP = high-sensitivity CRP   IL = interleukin   MI = myocardial infarction   NSTEMI = non–ST-segment elevation MI   STEMI = ST-segment elevation MI   sPLA2 = secretory type II phospholipase A2   UA = unstable angina

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