Heart Failure in Rheumatoid Arthritis: Rates, Predictors, and the Effect of Anti–Tumor Necrosis Factor Therapy Frederick Wolfe, MD, Kaleb Michaud, MS PURPOSE: We sought to determine the frequency of heart fail- ure in patients with rheumatoid arthritis, and to determine its predictors, particularly the use of anti–tumor necrosis factor (TNF) therapy. METHODS: Rheumatoid arthritis (n = 13,171) and osteoar- thritis (n = 2568) patients were studied during a 2-year period ending in June 2002. The diagnosis of heart failure was based on self-report or review of medical records. Propensity scores were used to adjust for the risk of anti-TNF (infliximab and etaner- cept) prescription. RESULTS: Heart failure was more common among patients with rheumatoid arthritis (3.9% [n = 461]) than in those with osteoarthritis (2.3% [n = 87]), after adjusting for differences in demographic characteristics. Patients with rheumatoid arthritis had similar risk factors for heart failure (e.g., hypertension, prior myocardial infarction, diabetes, advanced age) as persons in population-based studies. Heart failure was significantly (P 0.05) less common in anti-TNF–treated patients (3.1% [180/ 5832]) than in the remaining patients (3.8% [281/7339]), even after adjusting for baseline differences. In the absence of pre- existing cardiovascular disease, the risk of heart failure was low (0.4% [24/6251]) and was not related to anti-TNF therapy. CONCLUSION: Our results suggest that rheumatoid arthritis increases the risk of heart failure, which may be ameliorated by anti-TNF therapies. Am J Med. 2004;116:305–311. ©2004 by Excerpta Medica Inc. T here is now substantial evidence that rheumatoid arthritis is associated with increased cardiovascu- lar morbidity and mortality (1–12). Cardiovascu- lar manifestations of rheumatoid arthritis include peri- carditis, myocardial infarction, and heart failure (13), perhaps including diastolic dysfunction (14). Although the risk of myocardial infarction appears to be increased, little is known about the risk of heart failure in rheuma- toid arthritis. Heart failure is of special interest because the failing heart produces tumor necrosis factor (TNF), but the normal heart does not (15). Although the effects of circulating TNF- on cardiovascular function are un- certain (15–18), data from murine heart failure models support the theory that blockade of circulating TNF may ameliorate ventricular dysfunction (19,20). However, clinical trials of TNF blockade in patients with advanced heart failure have shown little benefit or even harm (17,21,22). It is not known whether anti-TNF therapy, which is being used increasingly in the treatment of rheu- matoid arthritis, affects the risk of heart failure in these patients. The purpose of this report was to determine the prev- alence of heart failure in patients with rheumatoid arthri- tis, in comparison with patients with osteoarthritis; to determine the factors associated with heart failure; and to study the effects of anti-TNF therapy on the risk of heart failure. METHODS Subjects were participants in the National Data Bank for Rheumatic Diseases study of the outcomes of arthritis. Patients are recruited for this ongoing study from the practices of U.S. rheumatologists (23–25), and are fol- lowed with semiannual questionnaires. Approximately 8% of patients decline to participate per year. This report includes 13,171 rheumatoid arthritis patients (including 3862 who were enrolled as part of an infliximab safety registry) who completed 35,064 biannual questionnaires during consecutive 6-month assessment periods ending in June 2002. In addition, data from 2568 patients with osteoarthritis of the hip or knee who were enrolled simi- larly were also analyzed for comparison. At each assessment, demographic and clinic variables are obtained (26 –35). Patients report all comorbid con- ditions, medications, and side effects of treatment. We obtained a history of pre-existing cardiovascular illness, current and previous hypertension, myocardial infarc- tion, and other cardiovascular conditions. We asked spe- cifically, “During the last 6 months were you diagnosed or treated for heart failure?” We also requested and reviewed records for all hospitalizations. Patients reporting heart failure were interviewed by the research staff using a stan- dardized, written protocol. A diagnosis of heart failure was considered valid if the patient provided data indicat- From the Arthritis Research Center Foundation (FW, KM) and the University of Kansas School of Medicine (FW), Wichita, Kansas. The infliximab registry is support by a grant from Centocor, Inc., Malvern, Pennsylvania. Requests for reprints should be addressed to Frederick Wolfe, MD, National Data Bank for Rheumatic Diseases, Arthritis Research Center Foundation, 1035 N. Emporia, Suite 230, Wichita, Kansas 67214, or fwolfe@arthritis-research.org. Manuscript submitted January 14, 2003, and accepted in revised form September 9, 2003. © 2004 by Excerpta Medica Inc. 0002-9343/04/$–see front matter 305 All rights reserved. doi:10.1016/j.amjmed.2003.09.039