Associations of plasma fibrinogen and factor VII clotting activity with coronary heart disease and stroke: prospective cohort study from the screening phase of the Thrombosis Prevention Trial

Summary.  Background: As with ‘conventional’ risk factors such as cholesterol and smoking, there is a need for large, long‐term prospective studies on hemostatic factors. Objectives: To investigate the prospective relationship of fibrinogen and factor VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and stroke in a study with a large number of outcomes over a period of 15 years. Patients/methods: A cohort of 22 715 men aged 45–69 years was screened for participation in the Thrombosis Prevention Trial. Men were followed up for fatal and non‐fatal CHD and stroke events. There were 1515 CHD events (933 CHD deaths) and 391 strokes (180 stroke deaths). Hazard ratios (HRs) and 95% confidence intervals are expressed per standardized increase in log fibrinogen and log FVIIc, adjusting for age, trial treatment group, conventional CHD risk factors and regression dilution bias. Results: Hazard ratios for fibrinogen were 1.52 (1.37–1.70) for all CHD events, and 1.36 (1.09–1.69) for all strokes. Exclusion of events within the first 10 years showed a persistent association between CHD and fibrinogen, with an adjusted HR of 1.93 (1.42–2.64). The HRs for FVIIc, adjusting for age and trial treatment, were 1.07 (1.01–1.12) for all CHD events and 1.07 (0.97–1.20) for all strokes, and the fully adjusted HRs were, respectively, 0.97 (0.84–1.05) and 1.07 (0.85–1.33). Conclusions: The persisting association between fibrinogen and CHD beyond 10 years may imply a causal effect. There is a small effect of FVIIc on CHD, after adjustment for age and trial treatment, but no association independent of other risk factors.

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