Abstract MP87: Association of Hemostasis Biomarkers with Intracerebral Hemorrhage: the REasons for Geographic and Racial Differences in Stroke Study (REGARDS)
Introduction: Risk factors for intracerebral hemorrhage (ICH) are poorly characterized. Deficiencies of fibrinogen and factors VIII, IX, and XI cause bleeding disorders but whether these factors relate to ICH risk is unknown.
Methods: REGARDS recruited 30,239 individuals ≥45 years from the contiguous US oversampling blacks (44%) and residents of the southeast (56%) from 2003-07. ICH were confirmed by medical record review. Biomarkers were measured in a case cohort study of ICH and a 1104 person cohort random sample. The hazard ratio (HR) and 95% confidence interval (CI) per standard deviation (SD) lower biomarker were estimated using Cox models adjusting for stroke risk factors (Table). Individuals on warfarin were excluded.
Results: Over a median 5.8 years (Interquartile range 4.1, 7.0) 66 ICH occurred. Compared with participants without ICH, participants with ICH were older (67 vs 65 years), more likely male (62 vs 44%), had higher aspirin use (53 vs 44%), higher systolic blood pressure (135 vs 127mmHg), and a greater prevalence of cardiovascular disease (26 vs 16%), left ventricular hypertrophy (61 vs 51%), and a lower prevalence of atrial fibrillation (5 vs 7%); all p <0.05. Only mean levels of factor IX (97% vs 104%; p <0.05) were lower in participants with vs those without ICH. Factor IX was significantly associated with ICH per SD lower increment (Table). Compared to the highest tertile of factor IX (>112%), the lowest tertile (<94%) was associated with a HR of 4.1 (95% CI 1.7, 9.8) and the middle tertile (94%-112%) with a HR of 2.3 (95% CI 0.9, 5.8) for ICH. Excluding individuals in lowest 2.5% (<66%) of factor IX levels did not change the results.
Discussion: Factor IX was associated with risk of ICH. As congenital factor IX deficiency is a bleeding disorder (hemophilia B), the observed gradation of risk, and the biologic plausibility, our results suggest a likely causal role for normal variation of factor IX levels and population ICH risk.
Author Disclosures: N. Zakai: None. S. Judd: None. N. Olson: None. D. Kleindorfer: None. B. Kissela: None. G. Howard: None. M. Cushman: None.
- © 2015 by American Heart Association, Inc.