Elevated Plasma Amylase Levels in Advanced Chronic Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy: Correlation with Circulating Interleukin-6 Activity

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Abstract
It has been reported that proinflammatory cytokine activation is associated with both mesenteric venous congestion and peripheral tissue underperfusion in advanced chronic heart failure. The aim of our study was to investigate if plasma amylase (as an easily approached marker of a low-grade peripheral organ injury caused by elevated systemic venous pressure and reduced cardiac output) is elevated in severe heart failure and if this elevation is correlated with cytokine and neurohormonal activation in the plasma of heart failure patients. Plasma levels of amylase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), norepinephrine, and renin activity were measured in 43 severe heart failure patients (ischemic, 28; dilated, 15; left ventricular ejection fraction [LVEF] 27 ± 3%; New York Heart Association [NYHA] classes III-IV), in 37 mild heart failure patients (ischemic, 26; dilated, 11; LVEF, 33 ± 5%; NYHA classes I-II), and in 20 age-matched and gender-matched healthy controls. NYHA III-IV heart failure patients exhibited significantly higher plasma levels of amylase (342 ± 19 vs. 174 ± 13 U/L, p < 0.01), TNF-α (6.2 ± 0.5 vs. 4.2 ± 0.3 pg/ml, p < 0.01), IL-6 (5.9 ± 0.3 vs. 4.4 ± 0.3 pg/ml, p < 0.05), GM-CSF (21.2 ± 2.7 vs. 4.1 ± 0.9 pg/ml, p < 0.001), and neurohormones (both p < 0.001) compared with NYHA I-II heart failure patients and healthy controls (amylase, 165 ± 11 U/L, p < 0.01; TNF-α, 2.7 ± 0.3 pg/ml, p < 0.001; IL-6, 3.2 ± 0.2 pg/ml, p < 0.01; GM-CSF, 3.1 ± 0.7 pg/ml, p < 0.001). Only in NYHA III-IV heart failure patients, plasma amylase levels were significantly correlated with plasma IL-6 activity (r = 0.86, p < 0.001), plasma norepinephrine levels (r = 0.82, p < 0.001) and right atrial pressure (r = 0.52, p < 0.05). Additionally, circulating IL-6 was also significantly correlated with plasma norepinephrine (r = 0.86, p < 0.001) and right atrial pressure (r = 0.57, p < 0.01). In conclusion, plasma amylase levels were elevated in severe heart failure patients and correlated well with circulating IL-6 activation, possibly as a result of both mesenteric venous congestion and impaired peripheral tissue perfusion observed in advanced chronic heart failure. However, the lack of association between plasma IL-6 and amylase levels in mild heart failure patients indicates an independent correlation of each variable with the functional status of the disease.