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CLINICAL RESEARCH

Leptin and the ventilatory response to exercise in heart failure

^* Mayo Clinic, Rochester, Minnesota, USA

Manuscript received April 18, 2003; revised manuscript received June 3, 2003, accepted June 9, 2003.

^* Reprint requests and correspondence: Dr. Virend K. Somers, Mayo Foundation, St. Mary's Hospital, DO-4-350, 1216 Second Street SW, Rochester, Minnesota 55902, USA.
somers.virend{at}mayo.edu

OBJECTIVES: The aim of the study was to test the hypothesis that leptin is involved in the regulation of ventilatory responses to exercise in chronic heart failure (CHF).

BACKGROUND: Exercise-induced hyperventilation is a negative prognostic factor in CHF. Studies in animals suggest that leptin, a hormone secreted by adipocytes, contributes to the regulation of respiration. Plasma leptin levels are elevated in non-cachectic CHF, suggesting the possibility that leptin might be involved in dysregulation of ventilation in CHF.

METHODS: We studied 50 patients with stable CHF without cachexia. All subjects underwent anthropometric measurements, resting echocardiography, pulmonary function tests, and a cardiopulmonary exercise test. The ventilatory response to exercise was assessed by calculating the VE/VCO₂ and VE/VO₂ slopes (VE = ventilation per unit time, VCO₂ = carbon dioxide production, VO₂ = oxygen consumption).

RESULTS: Using a multiple regression model, leptin was significantly and positively correlated with both VE/VCO₂ slope (regression coefficient = 0.87, F = 39.32, p < 0.001) and VE/VO₂ slope (regression coefficient = 0.84, F = 24.04, p < 0.001). This correlation was independent of age, gender, body mass index, body fat, ejection fraction, New York Heart Association functional class, pulmonary function, plasma norepinephrine, angiotensin II, brain natriuretic peptide levels, and medications. Also, the greatest VE/VCO₂ slope was seen in subjects in the highest tertile of leptin.

CONCLUSIONS: Leptin is an independent predictor of VE/VCO₂ slope in heart failure, and may be a link between metabolic, cardiovascular, and respiratory abnormalities in CHF.

Abbreviations and Acronyms   BMI = body mass index   BNP = brain natriuretic peptide   CHF = chronic heart failure   DLCO = diffusion capacity of the lung for carbon monoxide   EF = ejection fraction   FEV1 = forced expiratory volume in 1 s   FVC = forced vital capacity   NYHA = New York Heart Association   VCO2 = carbon dioxide production   VE = ventilation per unit time   VO2 = oxygen consumption

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