Associations between cachexia and metalloproteinases, haemodynamics and mortality in heart failure

Background Addressing cachexia in chronic heart failure (CHF) patients is an urgent issue in Japan, the most aged country in the world. We investigated the possible relationships between cachexia and, metalloproteinases and haemodynamics assessed by the cardiac catheterization. We also clarified the prognostic value of cardiac cachexia in the Japanese CHF population. Methods and results A total of 370 participants (median age, 69 years; 35% women) were included. The haemodynamic effects of cachexia were analysed by right heart catheterization. The serum levels of matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP), as myocardial collagen turnover markers, were also assessed. Cachexia was present in 88 patients (31%). Overall, 59 patients (16%) had all-cause death. Serum MMP-2 and TIMP-2 levels were higher in cachectic patients than in noncachectic patients (797.5 [649.0-1066.8] vs 610.0 [461.8-756.8] ng/mL; P = .004 and 39.0 [28.0-49.0] vs 24.0 [19.0-37.0] ng/mL; P = .008, respectively). Cachectic patients had greater values of pulmonary vascular resistance (PVR) (161.9 [119.4-225.4] vs 127.8 [90.7-164.8] dynes/sec/cm(-5), P = .020). Kaplan-Meier survival analysis demonstrated higher probabilities of all-cause death in the cachexia group (log-rank P = .010). Cox proportional hazards modelling showed cachexia was an independent predictor of mortality (hazard ratio, 1.89; 95% confidence interval, 1.06-3.37; P = .029). The random forest model showed that C-reactive protein, age, haemoglobin, PVR and MMP-2 were predictors of cardiac cachexia. Conclusions Cachexia, applying the globally accepted definition, was associated with adverse outcomes in the Japanese CHF population and accompanied by increased activity of MMP species and PVR.

Automated summary

This study investigated the possible relationships between cachexia, metalloproteinases, and haemodynamics in chronic heart failure patients in Japan, the most aged country in the world. The results showed that cachexia was associated with adverse outcomes and increased activity of MMP species and PVR in this population. Cachexia was also found to be an independent predictor of mortality, with specific biomarkers identified as predictors of cardiac cachexia.