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(Stroke. 2004;35:e65.)
© 2004 American Heart Association, Inc.

Research Reports

Absence of Association Between Polymorphisms in the Hemostatic Factor Pathway Genes and Carotid Intimal Medial Thickness

The Framingham Heart Study

Caroline S. Fox, MD, MPH; Martin G. Larson, ScD; Diane Corey, MA; DaLi Feng, MD; Klaus Lindpaintner, MD; Joseph F. Polak, MD, MPH; Philip A. Wolf, MD; Ralph B. D’Agostino, PhD; Geoffrey H. Tofler, MD Christopher J. O’Donnell, MD, MPH

From the National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Mass (C.S.F., M.G.L., D.C., P.A.W., R.B.D., C.J.O.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (C.S.F., C.J.O.); Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Mass (M.G.L., P.A.W.); Department of Internal Medicine, Boston Medical Center, Boston, Mass (D.F.); Roche Genetics, Basel, Switzerland (K.L.); Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (J.F.P.); Department of Mathematics, Boston University, Boston, Mass (R.B.D.); Royal North Shore Hospital, Sydney University, Australia (G.H.T.); and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Mass (C.J.O.).

Correspondence to Christopher J. O’Donnell, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702. E-mail chris{at}fram.nhlbi.nih.gov

Background and Purpose— Fibrinogen, plasminogen activator inhibitor-1, and other key proteins in the coagulation cascade have been implicated in the origin of cardiovascular disease. Polymorphisms in genes encoding these proteins have been associated with variability in plasma levels of these proteins. Carotid intimal medial thickness (IMT) is a heritable, quantitative measure of atherosclerosis that is predictive of subsequent myocardial infarction and stroke. We sought to test whether carotid IMT is associated with polymorphisms in several well-characterized genes in the hemostatic factor pathways.

Methods— Here, 867 men and 911 women (mean age, 57 years) in the Framingham offspring cohort underwent B-mode carotid ultrasonography to determine the mean internal (ICA) and common carotid artery (CCA) IMT. Age-, sex-, and multivariable-adjusted linear regression was used to estimate the association of the following variants with log-transformed CCA and ICA IMT: factor V Leiden, factor VII Arg/Gln, fibrinogen HindIII ß-148, plasminogen activator inhibitor-1 4G/5G, and the glycoprotein IIIa Pl^A2 polymorphism.

Results— Mean ICA IMT was 0.58 mm; mean CCA IMT was 0.60 mm. There were no differences in ICA or CCA IMT by genotype for any of the candidate genes in unadjusted, age- or sex-adjusted, and multivariable-adjusted models.

Conclusions— There is no evidence for an association between well-studied polymorphisms in the hemostatic factor genes and carotid IMT. Whether other common genetic variants in hemostatic factor genes are associated with subclinical atherosclerosis remains to be determined.

Key Words: coagulation • epidemiology • genetics • risk factors

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