Elevated fibrinogen levels and subsequent subclinical atherosclerosis: The CARDIA Study

Objective: To determine whether elevated levels of hemostatic factors are associated with the subsequent development of subclinical cardiovascular disease. Methods: Fibrinogen, factors VII (FVII) and VIII (FVIII), and von Willebrand factor (vWF) were measured in 1396 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Coronary artery calcification (CAC) and carotid intimal/medial thickness (CIMT) were determined 13 years later. The adjusted prevalence of CAC and mean CIMT across the quartiles of each hemostatic factor was computed for the total sample and for each race and gender group. Results: The age-, race-, and gender-adjusted prevalences of CAC with increasing quartiles of fibrinogen were 14.4%, 15.2%, 20.0%, and 29.1% (p < 0.001 for trend). This trend persisted after further adjustment for body mass index (BMI), smoking, educational level, center, systolic blood pressure (BP), diabetes, antihypertensive medication use, total and high-density lipoprotein (HDL) cholesterol, and CRP. A similar trend was observed for CIMT (age-, race- and gender-adjusted, p < 0.001; multivariable-adjusted, p = 0.014). Further analyses of race and gender subgroups showed that increasing quartiles of fibrinogen were associated with CAC and CIMT in all subgroups except black men. The prevalence of CAC was not associated with increasing quartiles of FVII, FVIII, or vWF, suggesting they may be less involved in plaque progression. Conclusion: An elevated fibrinogen concentration in persons aged 25-37 is independently associated with subclinical cardiovascular disease in the subsequent decade.