The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure

Gong, Kaizheng; Zhang, Zhengang; Sun, Xiaonin; Zhang, Xin; Li, Aihua; Yan, Junfeng; Luo, Qiuping; Gao, Yang; Feng, Yiliang

doi:10.1016/j.ahj.2005.02.040

« Previous Next »American Heart Journal
Volume 151, Issue 1 , Pages 62-68, January 2006

The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure

Kaizheng Gong, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
- Reprint requests: Kaizheng Gong, MD, Department of Cardiology, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou 225001, China.
Zhengang Zhang, MD, PhD
- Department of Clinics, Medical School of Yangzhou University, Yangzhou, China
Xiaonin Sun, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Xin Zhang, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Aihua Li, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Junfeng Yan, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Qiuping Luo, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Yang Gao, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China
Yiliang Feng, MD
- Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China

Received 25 May 2004; accepted 21 February 2005.

Background

Inflammatory mediators play an important role in the pathogenesis of chronic heart failure (CHF). Methotrexate (MTX) is used in the treatment of inflammatory-mediated diseases (eg, rheumatoid arthritis) because it modulates the expression of numerous inflammatory cytokines. However, no studies have assessed the effects of MTX on plasma levels of inflammatory mediators in patients with CHF.

Methods

In a prospective, randomized, placebo-controlled, single-blind study, 71 patients receiving conventional treatment were randomly allocated to either MTX group (7.5 mg once a week, n = 35) or placebo group (n = 36) with a follow-up of 12 weeks. The effects of MTX on plasma cytokine expression, left ventricular ejection fraction, left ventricular end-diastolic dimension, New York Heart Association (NYHA) functional class, 6-minute walk test distance, and quality of life (QOL) were determined in patients with CHF.

Results

Sixty-two patients completed the study. The circulating levels of inflammatory mediators in patients with CHF were markedly elevated compared with healthy controls (P ≤ .002). Methotrexate (n = 30) reduced plasma levels of tumor necrosis factor α (−15.6%, P < .05), interleukin 6 (−21.8%, P < .01), monocyte chemoattractant protein-1 (−22.6%, P < .01), soluble intercellular adhesion molecule-1 (−19.2%, P < .05), and C-reactive protein (−27.2%, P < .01) compared with baseline. Furthermore, interleukin 10 (15.8 %, P < .05) and soluble IL-1 receptor antagonist (36.1%, P < .01) expression was increased, whereas improvements in NYHA classification, 6-minute walk test distance, and QOL were found compared with baseline. Monocyte chemoattractant protein-1 expression was lower and soluble IL-1 receptor antagonist expression higher in the MTX than placebo group (n = 32). Furthermore, the left ventricular ejection fraction, left ventricular end-diastolic dimension, and incidence of main adverse cardiac events between the 2 groups were similar.

Conclusion

These results suggest that the addition of MTX to conventional therapy for CHF has significant anti-inflammatory effects and improves NYHA functional class, 6-minute walk test distance, and QOL.