Hemostatic factors as risk markers for intracerebral hemorrhage: a prospective incident case-referent study

Abnormalities in the hemostatic system may cause hemorrhagic complications. The aim of the present study was to examine whether total concentrations of tissue plasminogen activator (tPA), plasminogen inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and soluble thrombomodulin were associated with a first-ever intracerebral hemorrhage (ICH).

This prospective study was an incident case-referent study nested within the Västerbotten Intervention Program and the Northern Sweden Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) cohorts. By 2000, approximately 74 000 subjects had been screened, and 39 ICH cases were defined according to the World Health Organization MONICA criteria. A total of 78 matched controls were selected from the same cohort.

The average time from screening to the ICH event was 5.1 years. tPA/PAI-1 complex, systolic and diastolic blood pressures, and hypertension were associated with ICH in the univariate analysis. In the multivariate model, only hypertension (odds ratio [OR], 3.96; 95% confidence interval [CI], 1.27 to 12.36) and the tertile with the highest level of VWF compared with the lowest tertile (OR, 0.27; 95% CI, 0.08 to 0.90) were independently associated with ICH. The OR for the combined exposure to hypertension and low levels of VWF was 8.95, indicating a possible synergistic interaction. No associations were observed for smoking, cholesterol, body mass index, PAI-1, tPA, and soluble thrombomodulin.

This study showed that hypertension and low concentrations of VWF were independently associated with ICH. Furthermore, we observed a possible synergistic interaction between low levels of VWF and hypertension, suggesting 2 different pathways in the development of ICH.