Fibrinogen and D-dimer as risk factors for coronary heart disease in the Scottish Heart Health Study

In the Scottish Heart Health Study, 5093 men and 4862 women had their fibrinogen (Clauss assay) measured at baseline (1984-1987). Over the following 8 years discharges from hospital with a diagnosis of myocardial infarction, coronary artery surgical operations and deaths ascribed to coronary heart disease (CHD) were recorded for all subjects. Fibrinogen was assessed as a risk factor for both CHD death alone and for all coronary events. Account was taken of baseline CHD status. Of the 3930 men without CHD at baseline, 194 had a coronary event, of whom 54 died due to CHD. Of the 1067 men with CHD already at baseline, 195 had a coronary event, of whom 76 died due to CHD. For women the corresponding numbers are 3760-69-11 and 992-80-24. Age adjusted risk ratios by fibrinogen thirds were estimated from Cox regression models. Regardless of baseline status, men have about 40% higher risk in the middle third and nearly twice the risk in the upper third, compared to the lowest third. Women have somewhat different results depending upon baseline status. Those with baseline CHD have no elevated risk in the middle third, but 1.5-2 times the risk in the highest third, compared to the first. Women without baseline CHD have about 2.5 times the risk in the middle third and more than three times the risk in the highest third. Further adjustments for known coronary risk factors (smoking, blood pressure and cholesterol) reduce the risk ratios without entirely removing the effect of fibrinogen. There is no evidence of interaction between fibrinogen and these classical risk factors. These results add to the evidence that fibrinogen is both a primary and a secondary risk factor for CHD, in women as well as in men. A nested case-control study of fibrin D-dimer (AGEN) was performed in 248 cases of incident CHD and 762 controls, matched for baseline CHD, age, sex, district and time of examination. Baseline plasma D-dimer levels were higher in cases (median 92ng/ml: IQR 62-154) than in controls (85; 56133). The odds ratio for incident CHD in the upper tertile of D-dimer was 1.50 (95% CI 1.02, 2.22; p<0.05). D-dimer was related to fibrinogen in cases (r=0.19, p=0.003) and controls (r=0.18, p<0.001): adjustment for fibrinogen modified the predictive value of D-dimer only slightly. We conclude that D-dimer is a predictor of CHD in the general population, suggesting a role for increased fibrin turnover in the pathogenesis for CHD.