Antithrombin levels are associated with the risk of first and recurrent arterial thromboembolism at a young age

BACKGROUND AND AIMS: It is as yet unknown whether antithrombin levels are associated with arterial thromboembolism (ATE) at a young age. To investigate the association between antithrombin levels and premature and recurrent ATE, we performed a case-control study and a subsequent nested cohort study of premature coronary heart disease (CHD) patients. METHODS: In the case-control study, we included 571 patients who had a recent premature ATE, including CHD and ischemic stroke (IS), and 461 healthy controls. The association between antithrombin levels (dichotomized: ≤median vs. >median) and ATE was investigated. Subsequently we studied the association between antithrombin levels and recurrent cardiac events, ATE or death in a nested cohort of 323 CHD patients. RESULTS: Low antithrombin levels (≤median, 1.04 IU/mL) are associated with an increased risk of ATE (OR 1.46; 95% CI:1.09-1.96), after adjustment for classical cardiovascular risk factors. This was observed in the subgroups of CHD patients (1.43; 1.01-2.02) and IS patients (1.48; 1.01-2.19). CHD patients with low antithrombin levels had a higher risk of recurrent cardiac events (HR 2.16, 95% CI:1.07-4.38). Especially in women with low antithrombin levels, the risk of recurrent cardiac events was high (HR 5.97, 95% CI 1.31-27.13) as was the risk of recurrent ATE or death (HR 4.22, 95% CI 1.19-15.00). CONCLUSIONS: Individuals with relatively low antithrombin levels have an increased risk for ATE at a younger age. CHD patients with low antithrombin levels, especially women, have a higher risk of recurrent cardiac events.