Association of γ’ Fibrinogen with Risk Factors and Prevalent Cardiovascular Disease in the Framingham Heart Study.

Abstract Background: γ’ fibrinogen is a newly-emerging cardiovascular disease (CVD) biomarker that has shown significant associations with coronary artery disease in small case/control studies. γ’ fibrinogen is an isoform with an altered γ chain, and constitutes ∼10% of total fibrinogen. Both elevated γ’ and total fibrinogen cause fibrinolytic resistance in vitro. However, data are lacking from community based studies on the association of γ’ fibrinogen with CVD risk factors or with clinical CVD. Methods: γ’ fibrinogen levels were measured using an ELISA assay in 3284 men and women in the Framingham Heart Study Offspring Cohort 7th examination cycle (2002–05). Associations of γ’ fibrinogen were examined using linear regression for continuous CVD risk factors and logistic regression for prevalent CVD and other dichotomous measures. Results: The ELISA CV was 9.3% at mean γ’ fibrinogen levels. Participants (mean age 60 years, 53.4% women) with prevalent CVD (0.297 ± 0.007 mg/ml; mean ± SE) had significantly higher mean concentrations than those without CVD (0.255 ± 0.002 mg/ml). There were significant (all p<0.05) associations between γ’ fibrinogen levels with several cardiovascular risk factors, including age, BMI, systolic blood pressure, diabetes mellitus, cigarette smoking, and total cholesterol, and an inverse association with HDL cholesterol. γ’ fibrinogen was associated with prevalent CVD with an odds ratio of 1.76 (95% CI 1.06–2.92) for the highest compared to the lowest tertile, after adjustment for all of the above risk factors. As expected, since γ’ fibrinogen constitutes a subset of total fibrinogen, γ’ fibrinogen was correlated with total fibrinogen. However, if we included both γ’ and total fibrinogen in further analyses of association with CVD, the odds ratio was 3.08 (95% CI 1.41–6.72) for the combined tertile of both the highest γ’ fibrinogen and highest total fibrinogen, an odds ratio that was substantially higher than that for either marker alone. Conclusions: γ’ fibrinogen is associated with multiple CVD risk factors and with prevalent CVD, accounting for CVD risk factors, over and above total fibrinogen alone. Prospective studies are warranted to examine the ability of γ’ fibrinogen to predict CVD.