Independent Association Between Plasma Leptin Levels and Heart Rate in Heart Transplant Recipients

Abstract

Background-Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies.The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. Methods and Results-We studied 32 male patients (mean age, 56.5Ϯ9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (rϭ0.47, Pϭ0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (rϭ0. 73, PϽ0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (Fϭ2.61, Pϭ0.017). We also observed a strong, independent association between leptin levels and body mass index (Fϭ5.8, PϽ0.00001). Conclusions-We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors. Key Words: leptin Ⅲ heart rate Ⅲ transplantation H eart rate is emerging as an important cardiovascular risk factor, and it may predict the development of sustained hypertension. 1 Autonomic neural and humoral mechanisms contribute to the control of heart rate. Leptin, the 167 amino acid product of the ob gene, 2 has also been linked to cardiovascular risk. 3,4 Animal studies show that chronic leptin infusion increases heart rate and blood pressure. 5,6 High leptin levels are linked to poor prognosis in the setting of myocardial infarction. 4 In human studies, plasma leptin levels correlate strongly with heart rate, most strikingly during sleep. [7][8][9] The effects of leptin on heart rate are presumably mediated by the central effects of leptin as it modulates autonomic neural control of the heart. 5,6 However, there is emerging evidence that leptin may have direct, non-neural effects on cardiovascular function. Leptin receptors or their mRNA have been detected in blood vessels and in the heart. 10 -13 The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. Methods SubjectsWe studied 32 male patients (aged 56.5Ϯ9.3 years; range, 41 to 74 years). Subjects were selected across a broad spectrum of time intervals after transplantation (mean time after transplantation, 56Ϯ8 months; range, 1 to 132 months). Acute rejection, significant graft vasculopathy (stenoses Ն50%), and impaired systolic function were excluded by endomyocardial ...

Leptin and hyperleptinemia - from friend to foe for cardiovascular function

“…Such a relationship may be transposed into a direct correlation between left ventricular size and plasma leptin levels. While it seems reasonable that the higher heart rate under hyperleptinemia may be due to leptin-induced sympathetic activation, an independent association between leptin levels and heart rate was observed in heart transplant recipients with sympathetic denervation (Winnicki et al 2001). This finding suggests a direct effect of leptin on heart rate conceivably through cardiac leptin receptors, although direct effects of leptin on the cardiac conducting system and cardiac growth still warrant further study.…”

Arterial Load and Ventricular-Arterial Coupling

“…There may be various reasons why these allometric relationships would differ from theoretical predictions derived from fractal models, including deviations from model theoretical assumptions, differences in the metabolic rates of different tissues (which may vary systematically with body size even within normal ranges of body weight) and the effects of various neurohormonal pathways that may exert direct distant effects on the heart and vasculature independently of local flow phenomena. For example, leptin secreted by adipocytes bears a strong relationship with body weight and is known to affect heart rate both through direct effects on the heart26 and through autonomic regulation. This heart-rate increasing effect would be expected to counterbalance the strong and highly non-linear negative relationship between body mass and heart rate that would be predicted purely on the basis of from fractal-network theory 25, 26…”

“…For example, leptin secreted by adipocytes bears a strong relationship with body weight and is known to affect heart rate both through direct effects on the heart26 and through autonomic regulation. This heart-rate increasing effect would be expected to counterbalance the strong and highly non-linear negative relationship between body mass and heart rate that would be predicted purely on the basis of from fractal-network theory 25, 26…”

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors

“…Leptin has been associated with impaired fibrinolysis [6,7], hypertension [8] and calcification of vascular cells [9]. In addition, plasma leptin concentrations are raised in patients with congestive heart failure [10] and correlate with heart rate in heart transplant recipients [11]. Moreover, some authors have proposed hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk [12] while others have shown that leptin is an independent risk factor for coronary events in hypercholesterolemic men [13].…”