von Willebrand factor and coronary heart disease: prospective study and meta-analysis.

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 >126 IU.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 <90 IU.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.