Thrombin generation markers and coronary heart disease risk factors in a Polish population sample.

ABSTRACT

Thrombosis plays a major role in the development of atherosclerosis and its acute vascular complications. Epidemiological studies have shown that elevated levels of plasma fibrinogen are associated with an increased risk of coronary heart disease (CHD). It is not clear whether this association is linked to hemostatic functions of fibrinogen which serves as a substrate for thrombin. Generation of thrombin in vivo can be evaluated by measurement of its specific markers in plasma, i.e. thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2). We determined plasma levels of TAT and F1 + 2 in a population sample of southeastern Poland and evaluated relations of these markers with plasma fibrinogen, factor VII coagulant activity (FVIIc), and other known CHD risk factors. The population studied consisted of 215 men and 251 women, aged 43-75 years. Final analysis was performed on 195 men and 222 women. The distribution of plasma TAT and F1 + 2 concentrations were highly skewed with the higher median values for women than for men. Log values of TAT correlated with log values of F1 + 2 in men (r = 0.27, p < 0.01) and in women (r = 0.15, p < 0.05). In the regression analysis both markers were positively related to age in women but not in men. After adjustment to age there was a positive relation between TAT and fibrinogen in both sexes. In women, but not in men, F1 + 2 showed a positive association with FVIIc. Total plasma cholesterol was negatively related to TAT in women only. There was no association between thrombin generation markers and plasma triglycerides, HDL-cholesterol, LDL-cholesterol, blood pressure, cigarette smoking and body mass index (BMI). The association of plasma fibrinogen and FVIIc with thrombin generation markers points to an important role of the hemostatic system in the pathogenesis of atherosclerosis and coronary heart disease in humans.