A prospective study of fibrinogen and risk of myocardial infarction in the Physicians' Health Study

Abstract

Objectives: We examined the association of baseline plasma fibrinogen with future risk of myocardial infarction (MI) in the Physicians' Health Study.

Background: Elevated plasma fibrinogen increases and low dose aspirin decreases risk of MI. However, prospective data are limited about their interrelationships.

Methods: Blood samples were prospectively collected at baseline from 14,916 men in the Physicians' Health Study, aged 40 to 84 years, who were randomly assigned to take aspirin (325 mg every other day) or placebo for 5 years. We measured baseline plasma fibrinogen among 199 incident cases of MI and 199 age- and smoking-matched control subjects free of cardiovascular disease at the time of the case's diagnosis.

Results: Cases had significantly higher baseline fibrinogen levels (geometric mean: 262 mg/dl) than did control subjects (245 mg/dl, p = 0.02). Those with high fibrinogen levels (> or =343 mg/dl, the 90th percentile distribution of the control subjects) had a twofold increase in MI risk (age- and smoking-adjusted relative risk = 2.09, 95% confidence interval = 1.15 to 3.78) compared with those with fibrinogen below 343 mg/dl. Adjustment for lipids and other coronary risk factors as well as randomized aspirin assignment did not materially change the result. Furthermore, we observed no interaction between fibrinogen level and aspirin treatment.

Conclusions: Among these apparently healthy U.S. male physicians, fibrinogen is associated with increased risk of future MI independent of other coronary risk factors, atherogenic factors such as lipids and antithrombotics such as aspirin.