SummaryIn two cohorts of patients on oral anticoagulant therapy, routinely treated by the Leiden Thrombosis Service, the frequency of major bleeding complications was assessed during two years (1988 and 1991). With Poisson regression analysis the influence of the risk factors age, sex, target zone, achieved INR and type of coumarin derivative used were determined. Subsequently, a bleeding risk index was calculated, combining the results of the two cohorts. For various types of patients the relative risk of major bleeding complications was assessed.Age and achieved INR were the most important and consistent risk factors: rate ratio (RR) for age in 1988 1.46 per 10 years increase (95% confidence interval [Cl] 1.20-1.78) and in 1991 1.57 per 10 years increase (95% Cl 1.23-2.00); RR per unit increase in achieved INR in 1988 1.42 (95% Cl 1.21-1.68) and in 1991 1.44 per unit increase in achieved INR (95% Cl 1.18-1.74). Two methods were used to combine the results of 1988 and 1991. In the first method the mean bleeding risk index was calculated: In (incidence) [natural logarithm of the incidence rate of major bleeding] = -5.64 +0.42 * age +0.26 % sex -0.29 * target range +0.36 % achieved INR -0.36 * coumarin type. In the second method only the consistent risk factors age and achieved INR were used: In (incidence) = -5.64 +0.42 % age +0.36 % achieved INR. These bleeding risk indexes can be used to assess the risk of major bleeding complications of individual patients and allow more individualized care by individual tailoring the desired anticoagulation.

SummarySeveral studies have examined the relation between factor VII and coronary artery disease by measuring factor VII levels in plasma and some found an association between high levels and disease. This suffers problems of interpretation concerning the causality of high factor VII levels, because factor VII levels may be affected by atherogenic risk factors and may become elevated as a consequence of atherosclerosis. We investigated the association between a genetic variant (353Arg→Gln), shown to be related to factor VII levels, and myocardial infarction in a large case-control study, including 560 cases and 644 controls. Individuals carrying the 353Arg-Arg genotype seemed to have a lower risk of myocardial infarction (odds ratio 0.80 [95% confidence interval 0.60-1.06]). In this study, we confirmed higher factor VII antigen and activity level in 529 men homozygous for the 353Arg allele compared with 115 men carriers of the 353Gln allele (around 20% higher).Our results indicate that a genetic propensity to high factor VII levels is not associated with the risk of myocardial infarction. Since we confirmed the association of the 353Arg-Arg genotype with higher factor VII levels, we conclude that high levels of factor VII are not a causal determinant of myocardial infarction.

SummaryRecently, it has been described that elevated plasma levels of factor VIII are a strong risk factor for venous thrombosis. We analysed the data of the Leiden Thrombophilia Study, a population based case-control study on the causes of venous thrombosis, to verify whether the risk due to oral contraceptive use was higher in women with higher factor VIII levels. Furthermore we investigated the joint risk of high factor VIII levels and oral contraceptive use.We selected 155 premenopausal women with deep-vein thrombosis and 169 control subjects, aged 15-49, who were at the time of their thrombosis (or similar date in control) not pregnant, nor in the puerperium, did not have a recent miscarriage, and were not using injectable progestogens. Of the patients, 109 (70%) women had used oral contraceptives during the month preceding their deep-vein thrombosis, in contrast to 65 (38%) of the control subjects (index date), yielding an odds ratio for oral contraceptive use of 3.8 (95% CI 2.4-6.0). Of the women who suffered a deep-vein thrombosis 56 (36%) had high factor VIII levels (≥150 IU/dl) as compared with 29 (17%) of the control subjects, yielding an odds ratio for high factor VIII of 4.0 (95% CI 2.0-8.0), relative to factor VIII levels <100 IU/dl. The joint effect of oral contraceptive use and high factor VIII resulted in an odds ratio of 10.3 (95% CI 3.7-28.9), comparing women who had both with women who had neither. We conclude that there is an increase in risk due to oral contraceptive use in women with higher factor VIII levels and that both factors have additive effects.

The natural history of radiological changes in the lumbar spine was evaluated in two groups of middle aged Dutch women selected from the general population. One group (n=236) had recurrent back pain and the other (n=241) had never experienced back pain. At the beginning of the study disc degeneration was more common in the group with back pain. Osteoporotic vertebral fractures were equally common in both groups. Nine years later both groups showed an increase in prevalence of disc degeneration and osteoporotic fractures. The strongest predictor for change in disc degeneration was the presence ofdegeneration at the beginning of the study. The development of disc degeneration for the first time was related to body mass index.

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