A prospective cohort study on the absolute incidence of venous thromboembolism and arterial cardiovascular disease in asymptomatic carriers of the prothrombin 20210A mutation

The prothrombin 20210A mutation has been associated with an increased risk for venous thromboembolism (VTE) and arterial cardiovascular disease. The risks for asymptomatic carriers of this mutation have thus far been studied only in case-control and retrospective cohort studies. Here we present the results of the first prospective observational study in asymptomatic first-degree family members of patients with either VTE or premature atherosclerosis and the prothrombin 20210A mutation. We included 464 individuals (236 carriers) with a total follow-up duration of 1816 years (943 years for the carriers). The annual incidence of a first VTE was 0.37% (95% CI, 0.08-1.08) for carriers and 0.12% (95% CI, 0.00-0.69) for noncarriers (HR, 3.1; 95% CI, 0.3-29.6). The annual incidence of a first arterial cardiovascular event was 0.56% (95% CI, 0.18-1.31) for carriers and 0.73% (95% CI, 0.27-1.58) for noncarriers (adjusted HR, 0.7; 95% CI, 0.2-2.5). We conclude that the absolute incidence of a first VTE or arterial cardiovascular event is low; therefore, the clinical implications of carriership of the prothrombin 20210A mutation are limited, and routinely testing all first-degree relatives of probands with this mutation does not appear to be justified.