Guanylin peptides in heart failure

This study investigated the role of prouroguanylin (ProUGN) and proguanylin (ProGN), members of a novel class of peptides with natriuretic activity in heart failure (HF), a disorder of declining cardiac output associated with disturbed sodium and water homeostasis. The hypothesis was that ProUGN and ProGN activity is dysregulated in chronic and acute HF. Plasma ProUGN and ProGN were measured in 243 patients with chronic stable HF and plasma ProUGN and cGMP, an intracellular mediator of ProUGN activity, measured in 336 patients admitted to hospital with acute HF using immunoassays. ProUGN and cGMP levels were repeated in acute HF patients prior to discharge. The primary endpoints were all cause mortality, HF readmission and either outcome at 180 days. ProUGN and ProGN were significantly greater in patients with chronic HF compared to controls and inversely correlated with eGFR. ProUGN and ProGN were significantly greater in patients with hypertension and in those taking diuretics, with higher levels associated with increased severity of HF as assessed by NYHA class. In multivariate analysis, eGFR was the only independent predictor of plasma ProUGN and ProGN level. ProUGN and cGMP were significantly lower in patients with acute HF compared to in controls. Pre-discharge ProUGN and cGMP were significantly greater than at admission, with pre-discharge ProUGN significantly greater than in controls. Admission ProUGN was significantly greater in patients who died and a greater pre-discharge ProUGN was significantly associated with increased risk of early mortality. Pre-discharge cGMP levels were significantly lower in those readmitted with HF compared to those not, with higher levels significantly associated with reduced risk of early HF readmission. A greater pre-discharge ProUGN/cGMP ratio was significantly associated with increased risk of mortality or HF readmission. These results suggest that adverse outcomes in HF may be associated with hyporesponsiveness to ProUGN.