Novel hemostatic factor levels and risk of ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study

Cerebrovasc Dis. 2010;29(5):497-502. doi: 10.1159/000297966. Epub 2010 Mar 19.


Background and objective: The role of hemostatic factor levels in cerebral infarction remains uncertain. We studied the association of levels of several under-studied hemostatic factors with ischemic stroke in a population-based cohort.

Methods: The Atherosclerosis Risk in Communities (ARIC) study includes 15,792 individuals aged 45-54 years at intake. Hemostatic factors II, V, IX, X, XI, XII, plasminogen and alpha(2)-antiplasmin were measured on frozen citrate plasma samples from 1990 to 1992. A case-cohort design was used, including all incident ischemic strokes (n = 89) over a median of 7.5 years and a stratified cohort random sample (n = 412). To determine the association of hemostatic factors with incident ischemic stroke, we computed hazard ratios (HRs) using multivariate proportional hazard regression analyses adjusted for demographic and other cardiovascular risk factors.

Results: The cohort random sample had a mean age (SD) of 56.9 (5.4) years and 42% were men. The age-, sex- and race-adjusted HRs for highest versus lowest quartiles were: factor XI (2.74, 95% CI 1.42-5.29), factor IX (1.92, 95% CI 0.99-3.73), and alpha(2)-antiplasmin (2.24, 95% CI 1.16-4.33). Correspondingly, the HRs of ischemic stroke per SD increment of factors XI, IX, and alpha(2)-antiplasmin were 1.64, 1.46 and 1.52, respectively (all p < 0.05). After multivariate adjustment including other clinical variables, the standardized HR remained significant for factor XI (1.50, 95% CI 1.10-2.05), but no other factor.

Conclusion: A greater level of factor XI was associated with an increased risk of ischemic stroke. Higher factor XI levels might help identify patients at elevated ischemic stroke risk.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifibrinolytic Agents / metabolism
  • Atherosclerosis / blood*
  • Biomarkers / blood
  • Blood Coagulation Factors / metabolism*
  • Case-Control Studies
  • Cohort Studies
  • Factor XI / metabolism
  • Female
  • Hemostasis*
  • Humans
  • Male
  • Middle Aged
  • Plasminogen / metabolism
  • Prospective Studies
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Stroke / blood*
  • Stroke / epidemiology*


  • Antifibrinolytic Agents
  • Biomarkers
  • Blood Coagulation Factors
  • Plasminogen
  • Factor XI