Activation of a novel natriuretic endocrine system in humans with heart failure.
Résumé
Objectives: To investigate whether plasma proguanylin and prouroguanylin levels are increased in patients with heart failure and evaluate their relationship with cardiac and renal function. Background: Proguanylin and prouroguanylin are the inactive precursors of guanylin and uroguanylin, natriuretic peptides involved in the regulation of sodium balance. Urine uroguanylin levels have previously been found to be elevated in patients with heart failure. Methods & Results: In this prospective observational study we recruited 243 patients with heart failure (151 men), and 72 healthy controls. In heart failure patients, plasma levels of proguanylin (median 7.2 µg/L range [0.9 to 79.0]) and prouroguanylin (8.3 µg/L [1.7 to 53.0]) were both significantly higher compared to in healthy controls (5.5 µg/L [0.4 to 22.3]), p < 0.0005 and (6.3 µg/L [2.5 to 16.9]), p < 0.0005 respectively. In patients with heart failure, increased age, history of hypertension, diabetes, atrial fibrillation, use of diuretics, higher NYHA class and lower eGFR were significant univariate predictors of proguanylin and prouroguanylin level. In multivariate analysis a history of hypertension and low eGFR both had strong independent association with proguanylin and prouroguanylin level. Proguanylin and prouroguanylin varied significantly between NYHA class with a trend of increasing plasma concentration with worsening severity of symptoms. Conclusions: Plasma proguanylin and prouroguanylin are elevated in patients with heart failure. Elevated plasma proguanylin and prouroguanylin levels are associated with hypertension, renal impairment and increasing severity of heart failure. This novel endocrine system may contribute to the pathophysiology of heart failure.
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