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European Heart Journal Advance Access published online on July 10, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn331
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the PRIME Study

Jean-Philippe Empana1,*, Florence Canoui-Poitrine1, Gerald Luc2,3,4, Irene Juhan-Vague5, Pierre Morange5, Dominique Arveiler6,7, Jean Ferrieres8, Philippe Amouyel3,4,9, Annie Bingham1, Michelle Montaye3,4,9, Jean-Bernard Ruidavets8, Bernadette Haas6,7, Alun Evans10, Pierre Ducimetiere1 on behalf of the PRIME Study Group

1 INSERM, Unit 909, Faculty of Medicine, Univ Paris-V, F-94807 Villejuif, France
2 Department of Atherosclerosis, INSERM, U545, Lille, France
3 Institut Pasteur de Lille, Lille, France
4 Université de Lille 2, Lille, France
5 Laboratory of Haematology, INSERM, U626, Hôpital La Timone, Marseille, France
6 Strasbourg MONICA Project, Laboratoire d'Epidemiologie et de Sante Publique, EA1801, Strasbourg, France
7 Faculte de Medecine, Universite Louis Pasteur, F-67085 Strasbourg, France
8 Toulouse MONICA Project, INSERM U558, Département d'Epidemiologie, Universite Paul Sabatier-Toulouse Purpan, Toulouse, France
9 Lille MONICA Project, INSERM, U744, Lille, France
10 Department of Epidemiology and Public Health, Queen's University, Belfast, Northern Ireland

Received 10 January 2007; revised 26 May 2008; accepted 19 June 2008.

* Corresponding author: INSERM U909, Cardiovascular epidemiology and sudden death, Hopital Paul Brousse, 16 Avenue Paul Vaillant Couturier, Villejuif 94807, France. Tel: +33 1 45 59 51 00, Fax: +33; 1 47 26 94 54, Email: jean-philippe.empana{at}inserm.fr

Aims: To compare whether novel inflammatory and haemostatic biomarkers are more predictive of well-characterized incident acute coronary syndrome (ACS) than stable angina (SA).

Methods and results: We used data from the PRIME Study, a prospective cohort of 9758 asymptomatic middle-aged men recruited in Northern Ireland and France between 1991 and 1993. A nested case–control study was established with the baseline plasma sample of 269 incident cases and 538 matched controls. Odds ratios (ORs) for SA and ACS were estimated by conditional logistic regression analysis. After 5 years of follow-up, 107 incident SA and 162 ACS cases were validated. After adjustment for traditional risk factors, higher circulating levels of hs-CRP, ICAM1, interleukin 6 and interleukin 18 were equally predictive of SA and ACS (all P-values of OR comparison >0.05). In contrast, elevated levels of fibrinogen, von Willebrand factor, and possibly higher level of D-dimers and lower level of tissue factor pathway inhibitor were associated with ACS only. The comparison of the ORs showed a statistically significant difference for von Willebrand factor only [OR4th vs. 1st quartile = 2.99 (1.49–6.02) for ACS vs. 0.80 (0.33–1.94) for SA; Pz test = 0.02].

Conclusion: This is the first population-based study suggesting that higher levels of circulating haemostatic markers and of von Willebrand factor, in particular, are significantly more predictive of incident ACS than SA.

Key Words: Epidemiology • Biomarkers • Angina pectoris • Acute coronary syndrome • Atherothrombosis


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