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High Plasma Levels of N-Terminal Pro-Atrial Natriuretic Peptide Associated With Low Anxiety in Severe Heart Failure

From the Departments of Psychosomatics and Psychotherapy (C.HL., M.K.), Cardiology (B.B., D.VL., B.P.), and Clinical Chemistry (L.B., J.S., W.S.), University of Göttingen, Göttingen, Germany.

Address reprint requests to: Christoph Herrmann-Lingen, MD, Department of Psychosomatics and Psychotherapy, University of Göttingen, von-Siebold-Strasse 5, D-37075 Göttingen, Germany. Email: cherrma{at}gwdg.de

Received for publication May 10, 2002; revision received August 7, 2002.

OBJECTIVE: Plasma levels of natriuretic peptides are elevated in congestive heart failure (CHF). These peptides show anxiolytic properties in studies of rodents and patients with panic disorder, but their possible effect on anxiety has never been studied in cardiac patients. We therefore assessed associations of the Atrial Natriuretic Pro-Peptide (pro-ANP) with anxiety in patients with CHF and controls.

METHOD: This was a cross-sectional study of 119 patients (46 with CHF, 76 controls with cardiovascular risk factors) in a tertiary care center. The study included assessment of CHF severity, ejection fraction, pro-ANP (microtiter assay), and psychosocial status (self-rating questionnaires for anxiety, depression, vital exhaustion, and quality of life).

RESULTS: The diagnosis and severity of CHF was significantly related to pro-ANP levels, bad physical quality of life, vital exhaustion, and depression. However, there was no significant effect of disease severity on anxiety. In CHF patients, pro-ANP was negatively correlated with anxiety ( = -0.30, p = .041). In the whole group, anxiety was independently predicted by vital exhaustion, depression, and younger age (overall adjusted R² = 0.48). Pro-ANP plasma levels showed an additional, inverse association with anxiety (ß = -0.17, p = .013, adjusted R² = 0.50). Predicted mean anxiety scores derived from this model showed a good fit with anxiety scores observed in subgroups defined by CHF severity.

CONCLUSION: Pro-ANP plasma levels are independently and inversely related to anxiety. Even in severe CHF with severely compromised quality of life, anxiety tends to decrease with high pro-ANP levels. This might be part of a negative feedback loop limiting psychological distress and its adverse autonomic consequences in severe heart failure.

Key Words: Pro-ANP, • congestive heart failure, • anxiety.

Abbreviations: ANOVA = analysis of variance;; ANP = atrial natriuretic peptide;; CHF = congestive heart failure;; HADS = Hospital Anxiety and Depression Scale;; LVEF = left ventricular ejection fraction;; MQ = Maastricht Questionnaire;; NYHA = New York Heart Association;; pro-ANP = N-terminal Pro-Atrial Natriuretic Peptide;; PTCA = percutaneous transluminal coronary angioplasty;; QoL = quality of life;; SF36 = Short Form 36 Health Survey.

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