Inflammation and future risk of symptomatic heart failure in patients with stable coronary artery disease.
BACKGROUND
Heart failure (HF) carries poor prognosis in coronary artery disease (CAD) patients despite advances in therapy. Inflammation predicts recurrent cardiovascular events in CAD patients. It is unknown whether increased levels of inflammatory markers are associated with incident HF in these patients.


OBJECTIVE
The aims of this study were to evaluate the association between inflammatory markers and future HF risk in patients with stable CAD and to explore possible mediation by myocardial infarction (MI).


METHODS
The study comprised 2,945 patients with stable CAD without HF at baseline during a median follow-up of 7.9 years. Inflammatory baseline markers were the basis of this study.


RESULTS
Heart failure was diagnosed in 508 patients (17.2%). Patients who developed HF were older and had more often previous MI, diabetes, hypertension, and peripheral vascular disease. Baseline levels of C-reactive protein (CRP), fibrinogen, and white blood cells (WBCs) were significantly higher in patients who developed HF compared with those who did not. Age-adjusted incident HF rates were related to elevated baseline inflammatory markers in a dose-response manner. Adjusting for multiple confounders, the HF hazard ratios were 1.38 (95% CI 1.11-1.72), 1.33 (95% CI 1.07-1.66), and 1.36 (95% CI 1.10-1.68) for the third tertiles of CRP, fibrinogen, and WBC levels, respectively. Hazard ratio for the fifth quintile of a combined "inflammation score" was 1.83 (95% CI 1.40-2.39). Mediation by MI preceding the HF onset during follow-up accounted for 10.4%, 10.8%, and 8.6% of the association of subsequent HF with CRP, fibrinogen, and WBC, respectively.


CONCLUSIONS
Increased levels of CRP, fibrinogen, and WBC are independently related to the incidence of HF in patients with stable CAD.
Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel. Electronic address: a_alon1@netvision.net.il.
Alon
A
Eisen
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Gertner Institute for Epidemiology and Health Research Policy, Sheba Medical Center, Tel-Hashomer, Israel.
Michal
M
Benderly
The Israel Society for the Prevention of Heart Attacks, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel.
Solomon
S
Behar
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Israel Society for the Prevention of Heart Attacks, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel.
Uri
U
Goldbourt
Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel.
Moti
M
Haim
D000367:Age Factors; D000368:Aged; D001629:Bezafibrate / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D015994:Incidence; D007249:Inflammation / Q000097:blood*; D007557:Israel / Q000453:epidemiology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D000960:Hypolipidemic Agents; D005340:Fibrinogen; D002097:C-Reactive Protein; D001629:Bezafibrate