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Plasma Urocortin 1 in Human Heart Failure

From the Department of Medicine (S.P.W., R.N.D., G.D.G.), Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand; and Christchurch Cardioendocrine Research Group (C.M.F., T.G.Y., A.M.R.) Department of Medicine, University of Otago, Christchurch, New Zealand.

Correspondence to Mark Richards, MD, PhD, DSc, FRACP, FRSNZ, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. E-mail mark.richards{at}cdhb.govt.nz

Received December 1, 2008; accepted June 19, 2009.

Background— The urocortins are emerging as potentially important contributors to neurohumoral regulation of the circulation with recent reports attributing a powerful array of hemodynamic, renal, and neurohumoral effects to the urocortins in cardiac failure. These peptides also seem to have cardioprotective effects in the setting of ischemia-reperfusion. Little is known concerning the plasma concentrations of the urocortins in health and disease. We have investigated plasma urocortin 1 as a potential diagnostic marker of heart failure and documented its relationships to symptoms, measures of cardiac function, and concurrent levels of other circulating neurohormones.

Methods and Results— In 299 patients with recent onset dyspnea or peripheral edema presenting to primary care, plasma urocortin 1 and other vasoactive hormones were assayed, and echocardiography was performed. Heart failure was present in 74 patients (25%) according to predefined diagnostic criteria. Urocortin 1 levels were increased in patients with heart failure and were related to functional class, clinical signs of heart failure, echocardiographic indicators of left ventricular dimensions and function, plasma creatinine, and concurrent circulating levels of plasma natriuretic peptides, adrenomedullin, and endothelin 1.

Conclusions— Plasma urocortin 1 is elevated in heart failure (in proportion to the degree of cardiac dysfunction) in concert with the generalized neurohormonal activation seen in this condition. Urocortin levels predict heart failure independent of age, history of previous myocardial infarction, diabetes, hypertension, fractional shortening, and N-terminal prohormone brain natriuretic peptide levels.

Key Words: urocortin • heart failure • cardiac natriuretic peptides • adrenomedullin • endothelin