Background and Purpose--Increased soluble thrombomodulin (sTM) concentration has been associated with recurrent coronary events, whereas in one prospective study it predicted fewer first-ever coronary events. One study found no relationship between brain infarction (BI) and sTM levels. Among all subjects of the Étude du Profil Génétique de l’Infarctus Cérébral (GENIC) cohort and those free of previous vascular history, we investigated the relationship between sTM level and BI risk, and among cases, its relationship with BI prognosis.

Methods--Patients with BI (n=492) were consecutively recruited from 12 centers. Hospital controls without a history of stroke (n=492) were individually matched for age, sex, and center. Blood samples were collected after hospitalization. Determination of sTM levels was centralized in a single laboratory.

Results--Soluble TM concentration significantly increased with age and hypertensive status, but was similar in cases and controls. With analyses restricted to 278 pairs of subjects with no previous vascular history, sTM concentration >59.6 µg/L (second and third tertiles compared with the first) was associated with fewer first-ever BI (adjusted odds ratio of 0.56 (95% CI, 0.35 to 0.89; P=0.014). Among the cases, increased sTM concentration was associated with a higher death rate after a median follow-up of 5.2 (1.4 to 6.4) years. The adjusted hazard ratio per 1 SD of sTM concentration increase (34.2 µg/L) was 1.19 (95% CI, 1.02 to 1.39; P=0.028).

Conclusion--Increased sTM concentration may be protective against BI in subjects with no previous vascular disease, whereas it may predict a fatal outcome in patients who have already had a BI. Consequently, sTM levels should be interpreted according to vascular history.