Additive Value of Immunoassay-Measured Fibrinogen and High-Sensitivity C-Reactive Protein Levels for Predicting Incident Cardiovascular Events

Abstract

Background— Current guidelines suggest measuring high-sensitivity C-reactive protein (hs-CRP) as an aid to coronary risk assessment in adults without cardiovascular disease (CVD). Whether other inflammatory biomarkers, such as fibrinogen, add further prognostic information is uncertain. Methods and Results— In a prospective study of 27 742 initially healthy middle-aged women, the associations of baseline immunoassay fibrinogen and hs-CRP measurements with incident CVD were examined over a 10-year follow-up period. Compared with women in the bottom biomarker quintile, age-adjusted hazard ratios (95% confidence intervals [CIs]) for incident CVD for quintiles 2 to 5 of fibrinogen were 1.10 (0.86 to 1.41), 1.30 (1.03 to 1.65), 1.46 (1.16 to 1.85), and 2.43 (1.95 to 3.02); for hs-CRP they were 1.48 (1.06 to 2.05), 1.70 (1.24 to 2.33), 2.20 (1.63 to 2.96), and 3.24 (2.43 to 4.31). After further adjustment for established risk factors, both biomarkers remained associated ( P for trend ≤0.001) with incident CVD (hazard ratio, 1.35; 95% CI, 1.07 to 1.71 for top fibrinogen quintile; and hazard ratio, 1.68; 95% CI, 1.22 to 2.29 for top hs-CRP quintile compared with the bottom quintiles). Further adjustment for the other biomarker resulted in hazard ratios of 1.23 and 1.56 ( P for trend=0.02 and 0.002), respectively. Although fibrinogen correlated positively with hs-CRP ( r s =0.41, P <0.001), the highest CVD risk was associated with elevated levels of both fibrinogen and hs-CRP: age-adjusted hazard ratio of 3.45 (95% CI, 2.60 to 4.57) for women with fibrinogen >393 mg/dL and hs-CRP >3 mg/L compared with <329 mg/dL and <1 mg/L, respectively. Conclusions— In this cohort of initially healthy women, baseline levels of fibrinogen measured with a high-quality immunoassay provided additive value to hs-CRP and traditional risk factors in predicting incident CVD.