Relationships of plasma factor VIIa-antithrombin complexes to manifest and future cardiovascular disease

AbstractBackground Low levels of free activated coagulation factor VII (VIIa) are normally present in plasma to prime the coagulation of blood in normal hemostasis and during thrombus formation. VIIa also circulates in inactive form, in complex with antithrombin (VIIaAT) formed when VIIa is bound to tissue factor (TF). This study evaluated VIIaAT in relation to cardiovascular disease (CVD). Methods We determined the plasma VIIaAT concentration in samples from the Stockholm Coronary Atherosclerosis Risk Factor (SCARF) study, a population-based case-control study of myocardial infarction (MI) and in samples from the Stockholm study of 60-years-old individuals, a prospective study of CVD. VIIaAT was measured with a sandwich ELISA that captures the complex between a monoclonal antibody to VIIa and a polyclonal antibody to AT. Results In the SCARF study (200 post-MI cases, 340 controls), VIIaAT was statistically significantly associated with patient status [odds ratio (95% confidence interval (CI)] 1.51 (1.09-2.08), p = 0.0126). The case-control differences were however small, with VIIaAT values that largely overlap between the two groups. When a nested case-control design (211 incident CVD cases and 633 matched controls) was applied on 5- to 7-year follow-up results of the Stockholm prospective study of 60-year-olds, plasma VIIaAT concentration was not associated with incident CVD (odds ratio (95% CI) 1.001 (0.997-1.005), p = 0.5447). Conclusions Plasma VIIaAT concentration had no predictive value for future CVD in our study population. Slightly increased plasma VIIaAT concentrations observed after MI may reflect processes that occur in connection with the acute event when TF and VIIa availability is increased.