Published online before print April 25, 2002, doi: 10.1161/01.ATV.0000020007.25154.62
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© 2002 American Heart Association, Inc.
Thrombosis |
Elevated Fibrinogen and Homocysteine Levels Enhance the Risk of Mortality in Patients From a High-Risk Preventive Cardiology Clinic
From the Departments of Cardiovascular Medicine (M.A., D.L.S., G.L.P., K.K.-M.), Section of Preventive Cardiology and Cardiac Rehabilitation (M.A., D.L.S., G.L.P.), and Clinical Pathology (K.K.-M.), The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to Dennis L. Sprecher, MD, The Cleveland Clinic Foundation, Section of Preventive Cardiology and Rehabilitation, Desk C 51, 9500 Euclid Ave, Cleveland, OH 44195. E-mail sprechd{at}ccf.org
Abstract— Fibrinogen (Fib) plays an important role in platelet aggregation and thrombus formation, and homocysteine (tHcy) causes endothelial dysfunction and injury. Therefore, an interaction toward an enhanced risk of thrombotic events and consequent mortality might be expected in patients with both factors elevated. To determine whether patients exposed jointly to high Fib and high tHcy were at increased risk of mortality, we compared them with those with only one or neither risk factors elevated. Prevalence of coronary artery disease (cross-section) and short-term mortality (30±14 months) were assessed in 2084 patients with available baseline tHcy and Fib. Upper quartiles were used to define high tHcy (>14.2 µmol/L) and high Fib (>382 mg/dL). Cox models adjusting for Framingham risk score, creatinine, and coronary artery disease status were used to estimate the risk of high tHcy and high Fib and their combinations. Mean age of the patients was 56±12 years (35% women) with 71 (3.4%) recorded deaths. Risk-adjusted longitudinal models showed a hazard ratio of 2.14 (P=0.03) for isolated high tHcy, 2.28 (P=0.02) for isolated high Fib, and 3.29 (P<0.001) for both high tHcy and high Fib in comparison with neither risk factor high. Independence of each parameter and lack of synergism was found on longitudinal as well as cross-sectional analyses. Conjoint elevation of Fib and tHcy increased the risk of death by approximately 3-fold in three years. Although no significant interaction between Fib and tHcy was demonstrated, both provided independent information after adjustment for traditional risk factors.
Key Words: fibrinogen • homocysteine • mortality • risk
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