Carine J. M. Doggen

The role of the intrinsic coagulation system on the risk of myocardial infarction is unclear. In the Study of Myocardial Infarctions Leiden (SMILE) that included 560 men younger than age 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 with 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 with 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 increase the risk.

Objective— Lipids, through effects on the coagulation and fibrinolytic systems, may contribute to the development of venous thrombosis. This association has been investigated in a few studies, with conflicting results. Methods and Results— We conducted a population-based, case-control study at a health maintenance organization in Washington State, to assess the association of serum lipid levels with the risk of venous thrombosis. Cases were 477 postmenopausal women with a first venous thrombosis during January 1995 through December 2001. Control subjects (1986) were a random sample of postmenopausal women. Medical records, computerized pharmacy databases, and a cancer registry served to collect data on lipid levels and risk factors for thrombosis. Total cholesterol levels were not associated with venous thrombosis. Only high HDL cholesterol levels were associated with a decreased risk of venous thrombosis after adjustment for hospitalization, malignancy, height and weight, postmenopausal hormone therapy, and vascular disease (for high-density lipoprotein [HDL] cholesterol levels >1.79 mmol/L versus those 1.05 mmol/L compared with women with lower levels. Conclusion— Elevated triglyceride levels were associated with a doubling of risk of venous thrombosis in postmenopausal women, whereas elevated HDL cholesterol levels were associated with a decreased risk.

The HR2 haplotype of the factor V gene, which contains the histidine to arginine substitution at position 1299, has been reported to be associated with reduced factor V levels. Because high factor V levels have been found to be associated with an increased risk of myocardial infarction, we examined how the presence of the R2 allele affected the risk of myocardial infarction in the case-control “Study of Myocardial Infarctions Leiden”. Among 560 men with a first myocardial infarction before the age of 70 years, 9.5% were heterozygous carriers of the R2 allele. The control group consisted of 646 men, in which 9.9% were heterozygous and 0.2% homozygous carriers of the R2 allele. The risk of myocardial infarction in the presence of the R2 allele was not increased (odds ratio, 0.9; 95% confidence interval 0.6 to 1.4). Exclusion of factor V Leiden carriers did not change this result. The risk was 4.4-fold increased for smokers who carried the R2 allele compared to non-smoking noncarriers. No synergy was found between metabolic risk factors and the presence of the R2 allele. We conclude that the risk of myocardial infarction for men in the presence of the R2 allele of the His1299Arg polymorphism is neither increased nor decreased.