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European Heart Journal 2002 23(22):1764-1770; doi:10.1053/euhj.2001.3237
Copyright © 2002 by the European Society of Cardiology.
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von Willebrand factor and coronary heart disease. Prospective study and meta-analysis

P.H. Whincupa,f1, J. Daneshb, M. Walkerc, L. Lennonc, A. Thomsonc, P. Applebyd, A. Rumleye and G.D.O. Lowee

a Department of Public Health Sciences, St George’s Hospital Medical School, London, U.K.
b Department of Public Health and Primary Care, University of Cambridge, U.K.
c Department of Primary Care and Population Sciences, Royal Free and University College London Medical School, U.K.
d Cancer Epidemiology Unit, Radcliffe Infirmary, Oxford, U.K.
e University Department of Medicine, Glasgow Royal Infirmary, Glasgow, U.K.

revised January 2, 2002; accepted February 27, 2002

Abstract

Aims To determine whether circulating von Willebrand factor concentrations are prospectively related to risk of coronary heart disease in the general population.

Methods and Results We measured baseline von Willebrand factor values in the stored serum samples of 625 men with major coronary events and in 1266 controls ‘nested’ in a prospective study of 5661 men aged 40–59 years, recruited from general practices in 18 British towns in 1978–1980 and followed up for 16 years for fatal coronary heart disease and non-fatal myocardial infarction. We conducted a meta-analysis of previous relevant studies to place our results in context. Men in the top third of baseline von Willebrand factor values (tertile cutoff >126IU.dl–1) had an odds ratio for coronary heart disease of 1·83 (95% confidence interval 1·43–2·35; 2P <0·0001) compared with those in the bottom third (tertile cutoff <90IU.dl–1), after adjustments for age and town. The odds ratio was little changed after further adjustment for risk factors (1·82, 95% CI 1·37–2·41), and was not significantly different in an analysis restricted to the 404 cases and 1007 controls without baseline evidence of coronary heart disease (odds ratio 1·53, 95% CI 1·10–2·12). A meta-analysis of all relevant population-based prospective studies (including the present study) yielded a combined odds ratio of 1·5 (95% CI 1·1–2·0). von Willebrand factor values were strongly correlated with Helicobacter pylori seropositivity and circulating concentrations of C-reactive protein (2 P<0·0001 for each), but not with smoking, blood lipids, or most other measured risk factors.

Conclusion Though circulating von Willebrand factor concentrations may be associated with incident coronary heart disease, further studies are needed to determine the extent to which this is causal. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

Key Words: Coronary heart disease, epidemiology, coagulation

f1 Correspondence: Professor Whincup, Department of Public Health Sciences, St George’s Hospital Medical School, London SW17 0RE, U.K.


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