Elevated Fibrinogen Predicts Atherosclerosis.

Elevated levels of hemostatic factors are observed in patients with atherosclerosis, but whether they promote plaque formation or are a consequence of the disease is uncertain. To examine this issue, we used data from a large biracial cohort of young adults (Coronary Artery Risk Development in Young Adults [CARDIA]) followed up for 13 years, to examine the relationships of hemostatic factors - fibrinogen, factors VII and VIII, and von Willebrand factor (vWF) - with coronary artery calcium (CAC) and carotid intimal-medial thickness (IMT). Complete data were available on 1382 participants, whose mean age was 32 years at enrollment. The age, race, and gender-adjusted prevalence of CAC for increasing quartiles of fibrinogen levels was: 14.0%, 15.0%, 19.6%, and 28.4% (p <0.001 for trend). After further adjustment for BMI, smoking, systolic BP, and total cholesterol, the prevalence of CAC for increasing quartiles of fibrinogen was 15.5%, 16.0%, 19.0%, and 26.4% (p <0.001 for trend). Similar trends were observed for IMT (age, race, and gender-adjusted, p<0.001; multivariable adjusted, p=0.022). When race and gender subgroups were further analyzed, the prevalence of CAC was associated with fibrinogen levels in women and white men after age adjustment, and in women on multivariable analysis. IMT scores adjusted for age were associated with elevated fibrinogen levels in all except black men, and in black women after multivariable adjustment (p=0.003). While the prevalence of CAC was not associated with increasing quartiles of FVII, FVIII, or vWF, IMT scores were associated with elevated FVII on multivariable analysis in white women (p=0.006) and with vWF antigen in white men on age-adjusted (p=0.004) and multivariable analysis (p=0.013). There were no significant associations of hemostatic factors with either the prevalence of CAC or IMT in black men. Participants were categorized as to whether they had 0, 1, or more than 1 hemostatic factors in the highest quartile. After adjustment for age, race, and gender, hemostatic group classification was associated linearly with the prevalence of CAC (p<0.001 for trend) and IMT score (p=0.01 for trend). In conclusion, the main finding from this study is that elevated levels of fibrinogen in persons aged 25 to 37 are associated with the later appearance of subclinical markers of cardiovascular disease. These associations were observed in whites and black women, but not black men. We suggest that atherosclerosis became established during the 13 year observation period, and that increased fibrinogen may have been a contributing factor or a marker for disease development.