Elevated Plasma Fibrinogen

Cause or Consequence of Cardiovascular Disease?

From the Department of Epidemiology and Biostatistics and the Netherlands Institute for Health Sciences, Erasmus University Medical School, Rotterdam (J.G. van der B., M.L.B., P.T.V.M. de J., A.H., D.E.G.); the Gaubius Laboratory, TNO-PG, Leiden (J.G. van der B., M.P.M. de M., F.H., C.K.); the Julius Center for Patient-Oriented Research, Utrecht University, Utrecht (J.G. van der B., M.L.B., D.E.G.); the Netherlands Ophthalmic Research Institute, Amsterdam (P.T.V.M. de J.); and the Department of Ophthalmology, Academic Medical Centre, Amsterdam (P.T.V.M. de J.), the Netherlands.

Correspondence to Prof D.E. Grobbee, Julius Center for Patient-Oriented Research, PO Box 80035, 3508 TA Utrecht, the Netherlands.

Abstract—An association between increased plasma fibrinogen and an increased risk for myocardial infarction (MI) is well established, but the nature of this association is subject to debate. Our aim was to shed light on the potentially causal nature of this association. We examined whether increased plasma fibrinogen, due to a condition that is independent of cardiovascular events, also increases the risk for MI. A case-control study was performed in 139 subjects with a history of MI and 287 control subjects selected from the Rotterdam Study, a population-based cohort of 7983 subjects aged 55 years and older. The genotype of the -455G/A polymorphism in the fibrinogen ß-gene was determined by polymerase chain reaction. Functional plasma fibrinogen levels were determined according to von Clauss. The plasma level of fibrinogen was significantly higher in subjects with one or two A alleles compared with subjects with the GG genotype: 3.8 (95% confidence interval [CI], 3.6 to 3.9) g/L and 3.6 (3.5 to 3.7) g/L, respectively. With increasing plasma fibrinogen level, the risk for MI increased gradually; a rise in fibrinogen of 1 g/L was associated with a 45% increased risk (odds ratio adjusted for age, sex, and smoking, 1.45; 95% CI, 1.12 to 1.88). There was no association between the genotype of the -455G/A polymorphism and the risk for MI. The -455G/A polymorphism is therefore associated with increased plasma fibrinogen levels but not with an increased risk for MI. These findings indicate that an increased plasma fibrinogen level due to this genetic factor does not increase the risk for MI.

Key Words: cardiovascular disease risk • thrombotic tendency • HaeIII polymorphism • ß-fibrinogen gene • -455G/A polymorphism

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