Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the caerphilly study.

We have previously reported that plasma fibrin D-dimer (a marker of turnover of cross-linked fibrin) showed a strong and independent association with incident ischaemic heart disease (IHD) in the Caerphilly Study cohort of 1,998 men aged 49-65. To establish the specificity of this finding, we assayed plasma samples from this cohort with a more specific assay for fibrin D-dimer: this showed an association with incident IHD which was at least as strong and independent as that for the original assay (odds ratio, OR for top fifth compared to bottom fifth 3.79; 95% CI 1.77-8.10; p < 0.0001). To establish potential causes of the increased fibrin turnover, we also assayed several potential markers of coagulation activation or thrombotic tendency (prothrombin fragment F1+2, thrombin-antithrombin complexes, factor VIIc, activated partial thromboplastin time [APTT] and activated protein C resistance): none of these variables were associated with incident IHD in this cohort. We suggest that further studies are required to establish the causes of increased cross-linked fibrin turnover, which is associated with incident IHD in the general population when measured by a specific assay.