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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4045-4051.
Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2005-12-023697.
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Submitted December 21, 2005
Accepted August 3, 2006
Levels of intrinsic coagulation factors and the risk of
myocardial infarction among men. Opposite and synergistic
effects of factors XI and XII
Carine JM Doggen*, Frits R. Rosendaal, and Joost CM Meijers
Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
* Corresponding author; email: c.j.m.doggen{at}lumc.nl.
The role of the intrinsic coagulation system on the risk of myocardial infarction is unclear. In the Study of Myocardial Infarctions Leiden (SMILE), including 560 men below the age of 70 with a first myocardial infarction and 646 control subjects, we investigated the risk of myocardial infarction for levels of factor XI (factor XIc) and factor XII (factor XIIc). Furthermore, the risks for factor VIII activity (factor VIIIc) and factor IX activity (factor IXc) were assessed.
Factor XIc was 113.0% in patients compared to 109.8% in control subjects (difference 3.2%; 95%CI 1.1-5.4%). The risk of myocardial infarction adjusted for age for men in the highest quintile compared to those in the lowest quintile was 1.8-fold increased (ORadj 1.8, 95%CI 1.2-2.7). In contrast, factor XIIc among patients with myocardial infarction was lower than in control subjects, respectively 93.0% and 98.6% (difference 5.6%, 95%CI 3.3-7.9 %). The odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 0.4 (ORadj 0.4, 95%CI 0.2 - 0.5). The highest risk was found among men with both high factor XIc and low factor XIIc (analyses in tertiles: ORadj 6.4, 95%CI 2.2-18.0).
Factor VIIIc increased the risk of myocardial infarction although not dose-dependently. Factor IXc increased the risk, odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 3.2 (ORadj 3.2, 95%CI 2.0-5.1).
Thus, factors XIc and XIIc have opposite and synergistic effects on the risk of myocardial infarction in men. Factor VIIIc and factor IXc increases the risk.
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