P4730Associations of cachexia and prognosis in patients with heart failure

Abstract

Background: Chronic heart failure is one of a number of disorders associated with the development of a cachexia. In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The pathophysiology of cardiac cachexia is multifactorial and several mechanisms such as overexpression of the cytokines, malabsorption and neurohormonal imbalance have been proposed. Purpose:We sought to find out whether the cachectic state in CHF provides additional prognostic information about major adverse cardiovascular event (MACE). In subgroup analysis, hemodynamic effect was analysed by right heart catheterization and matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP), as myocardial collagen turnover markers, were also assessed. Method: This study enrolled 370 patients with heart failure (mean 71.0 yrs). BMI, albumin, hemoglobin, c-reactive protein and lipid profile were analyzed. We assessed MACE during follow-up period (mean 150 months). Cachexia was defined as BMI <20 kg/m2 and albumin <3.2 g/dl or hemoglobin levels <12.0 g/dL or c-reactive protein levels >0.5 mg/dL. Right heart catheterization including pulmonary capillary wedge pressure (PCWP) was measured in 157 patients and pulmonary vascular resistance (PVR) was then calculated as (mPAP - PCWP)/cardiac output multiplied by 80. Circulating levels of MMP-2 and TIMP-2 were determined by ELISA in 171 patients. Result: Cachexia was present in 59 patients (15.9%). The proportion of female and hypertension and levels of brain natriuretic peptide were higher in cachectic patients as compared with noncachectic patients (P<0.05). Values of total cholesterol, triglyceride, low-density lipoprotein, cholinesterase, estimated glomerular filtration rate and ejection fraction were reduced in cachexia patients (P<0.05). In subgroup analysis, cachectic patients had greater values of PCWP and PVR (15.9+9.5 mmHg vs. 9.8+5.6 mmHg; P<0.05 and 200.0+92.4 dynes/sec/cm5 vs. 135.4+73.5 dynes/sec/cm5; P<0.05, respectively) and both MMP-2 and TIMP- 2 levels were higher than that of noncachectic patients (659.8+417.1 ng/ml vs. 495.4+514.9 ng/ml; P<0.05 and 40.7+40.6 ng/ml vs. 20.0+36.5 ng/ml; P<0.05, respectively). Kaplan-Meier survival analysis demonstrated higher probabilities of MACE in the Cachexia group (P=0.03). A multivariate Cox proportional hazard model showed that cachexia was an independent predictor of MACE (hazard ratio, 2.06; 95% confidence interval, 1.25-3.41; P=0.04). Conclusion: Cachexia was associated with the adverse outcome in heart failure patients accompanied by increased activity of MMP species and cardiac preload.