title: Associations of coagulation factors IX and XI levels with incident coronary heart disease and ischemic stroke: the REGARDS study.
abstract: Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks.
  
  
  
  Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Olson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.|Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Judd
authors.affiliation: Department of Neurology and Rehabilitation Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Kissela
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.|Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Safford
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Howard
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA.|Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Zakai
mesh_terms: D001741:Black or African American; D000368:Aged; D044383:Black People; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood* / Q000208:ethnology*; D005164:Factor IX / Q000378:metabolism*; D005172:Factor XI / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000208:ethnology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D014481:United States; D044465:White People
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005164:Factor IX; D002097:C-Reactive Protein; D005172:Factor XI
keywords: coagulation factor IX; coagulation factor XI; coronary heart disease; risk factors; stroke