Leptin and the ventilatory response to exercise in heart failure.

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/VCO(2) and VE/VO(2) slopes (VE = ventilation per unit time, VCO(2) = carbon dioxide production, VO(2) = oxygen consumption). RESULTS Using a multiple regression model, leptin was significantly and positively correlated with both VE/VCO(2) slope (regression coefficient = 0.87, F = 39.32, p < 0.001) and VE/VO(2) 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/VCO(2) slope was seen in subjects in the highest tertile of leptin. CONCLUSIONS Leptin is an independent predictor of VE/VCO(2) slope in heart failure, and may be a link between metabolic, cardiovascular, and respiratory abnormalities in CHF.