Proguanylin and
prouroguanylin are the inactive precursors of
guanylin and
uroguanylin,
natriuretic peptides involved in the regulation of
sodium balance. Urinary
uroguanylin levels have been found previously to be elevated in patients with HF (
heart failure). The aim of the present study was to investigate whether plasma
proguanylin and
prouroguanylin levels are increased in patients with HF and to evaluate their relationship with cardiac and renal function. In this prospective observational study, we recruited 243 patients with HF (151 men) and 72 healthy controls. In patients with HF, plasma levels of
proguanylin [median, 7.2 (range, 0.9-79.0) microg/l] and
prouroguanylin [8.3 (1.7-53.0 microg/l)] were both significantly (P<0.0005) higher compared with levels in healthy controls [5.5 (0.4-22.3 microg/l) for
proguanylin and 6.3 (2.5-16.9) microg/l for
prouroguanylin]. In patients with HF, increased age, a history of
hypertension, diabetes and
atrial fibrillation, use of
diuretics, a higher NYHA (New York Heart Association) class and a lower eGFR (estimated glomerular filtration rate) were significant univariate predictors of
proguanylin and
prouroguanylin levels. In multivariate analysis, a history of
hypertension and low eGFR both had strong independent associations with
proguanylin and
prouroguanylin levels.
Proguanylin and
prouroguanylin varied significantly between NYHA class with a trend of increasing plasma concentrations with worsening severity of symptoms. In conclusion, plasma
proguanylin and
prouroguanylin are elevated in patients with HF. Elevated plasma
proguanylin and
prouroguanylin levels are associated with
hypertension, renal impairment and increasing severity of HF. This novel endocrine system may contribute to the pathophysiology of HF.