Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa.

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty-two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom-limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night-time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free-living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI-; -35.1 +/- 8.7% versus -26.1 +/- 10.7%; P<0.05). Obviously, patients with a lower body mass index (BMI < 16 kg m(-2), n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo(2), and a lower maximal O(2) pulse (P<0.05). BMI was significantly correlated to peak Vo(2), maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.

Alteration of the QT rate dependence in anorexia nervosa.

Myocardial repolarization has been evaluated in patients with anorexia nervosa (AN) with conflicting results. The authors postulated that dynamic alterations in QT interval adaptation could characterize these patients. This study compared QT dynamicity along RR intervals from 24-hour ECG data of patients with and without AN. Twenty-five patients (23 women) fulfilling the Diagnostic and Statistical Manual (DSM IV) criteria for AN were included in the study. All underwent 24-hour ECG Holter recordings, allowing QT and RR measurements, and heart rate variability (HRV) analysis in free-living conditions. A group of 25 sex- and age-matched healthy subjects served as controls. Compared with controls, AN patients presented with relative bradycardia, more particularly during night periods but neither mean QT nor corrected mean QT length (calculated using Bazett formula) over the 24 hours of monitoring differed. However, QT/RR slope was found significantly enhanced compared with normals (-2.00 +/- 0.53 vs - 1.42 +/- 0.40) (P = 0.006): QT length related to heart rate was found longer for a heart rate <55 beats/min in AN. Mean 24-hours QT length appears unaltered in AN in the absence of electrolytic disorders. However, the QT/RR relationship was enhanced reflecting the specific autonomic imbalance encountered in this population. The clinical implications of such findings need to be discussed since an equivalent enhancement of QT/RR slope has been described after myocardial infarction in patients presenting life-threatening ventricular arrhythmias.

Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women.

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T3 were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.