ANTITHROMBIN AND ATHEROSCLEROSIS IN THE ROTTERDAM STUDY

Antithrombin is a potent inhibitor of thrombotic tendency. Whether ath erosclerotic disease is associated with high or low antithrombin is un clear. Studies of the relation between antithrombin and presence of ar terial disease have shown contrasting results. In the Rotterdam Study, a single-center, population-based cohort study of 7983 subjects aged 55 years and older, the association between atherosclerosis and antith rombin was evaluated. The ratio of ankle to arm blood pressure is a gr aded marker for atherosclerosis and provides the opportunity to invest igate nonlinear associations. In the first 1427 participants of the Ro tterdam Study who did not use anticoagulants, both antithrombin and th e ratio of ankle to arm blood pressure were measured. In men the assoc iation between the two was quadratic: antithrombin activity was increa sed in men with moderate peripheral arterial atherosclerosis compared with those without, and in men with more severe atherosclerosis it was decreased. In women the association was linear: a decreased ratio of ankle to arm pressure was associated with increased antithrombin activ ity. These associations were independent of smoking, body mass index, serum Lipids, fibrinogen, and factor VIIc. We propose that antithrombi n activity rises in response to increased risk of cardiovascular disea se and also in response to the presence of atherosclerosis, whereas an tithrombin may decrease with increasing severity of the atheroscleroti c process in men. This may explain the contrasting results found in pr evious studies. Changes in antithrombin over time might be useful in p redicting the risk of cardiovascular disease and progression.