Fibrinogen synthesis is increased in cachectic patients with chronic heart failure

Cachexia is common in chronic heart failure (CHF) and may be due to a combination of reduced appetite, and increased metabolic rate due to immune activation. This hypermetabolism, with an increase in acute phase protein turnover, also seen in cancer cachexia, might contribute to weight loss seen in severe CHF. We investigated the rate of hepatic fibrinogen synthesis by measuring the rate of incorporation of deuterated phenylalanine into circulating plasma fibrinogen.

14 male patients with CHF, 9 with a history of weight loss each received an infusion containing 3500 mg of l-phenylalanine and 350 mg [(2)H(5)]l-phenylalanine. Blood drawn at intervals allowed measurement of the rate of [(2)H(5)]-phenylalanine enrichment in fibrinogen by gas chromatography-mass spectrometry.

Cachectic and non-cachectic patients had similar age and CHF severity. Cachectic patients had lower body mass index (BMI), and corrected arm muscle area (CAMA). The logarithmic derivatives of CRP and IL-6 were greater in the cachectic than the non-cachectic subjects (0.99 (0.38) v 0.44 (0.35); p=0.015 and 1.25 (0.50) v 0.86 (0.15); p=0.09). Total plasma fibrinogen (TF), relative fibrinogen synthesis rate (FSR) and absolute synthesis rate (ASR) were greater in those with cachexia. There were inverse relationships between TF and indices of body habitus: CAMA (r=0.62; p<0.02) and BMI (r=0.55; p<0.05). TF was related to CRP (r=0.69; p<0.007).

Patients with CHF and cachexia have an increased hepatic fibrinogen synthesis rate related to the level of C-reactive protein. It is possible that increased protein turnover is one of the causes of weight loss in patients with severe heart failure.