International Journal of Cardiology 176 (2014) 1433–1434

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Letter to the Editor

Anabolic hormonal response to different exercise training intensities in men with chronic heart failure G. Caminiti a,⁎, F. Iellamo a,b, V. Manzi b, C. Fossati a, V. Cioffi a, N. Punzo a, J. Murugesan c, M. Volterrani a, G. Rosano a a b c

Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy Dipartimento di Medicina Interna, Università Tor Vergata, Rome, Italy Dipartimento di Medicina Fisica e Riabilitazione, Università Tor Vergata, Rome, Italy

a r t i c l e

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Article history: Received 2 August 2014 Accepted 5 August 2014 Available online 13 August 2014 Keywords: Anabolic hormones Heart failure Exercise

Anabolic hormonal deficiency affects a significant proportion of men with chronic heart failure (CHF) and contributes to the onset of an anabolic/catabolic imbalance ultimately leading toward skeletal muscle waist and cardiac cachexia [1]. Counteracting the anabolic deficit seems to play beneficial clinical effects in CHF patients. The increase of serum levels of testosterone and growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis obtained by exogen administration, improves key symptoms of CHF such as exercise intolerance and muscle fatigue and positively impact quality of life [2,3]. Besides the exogen administration, an increase of the levels of anabolic hormones can be obtained through physical exercise. In healthy subjects testosterone may increase remarkably as an acute response to both endurance [4] and heavy resistance exercise [5]. Similarly, GH concentrations generally increase in response to both strength and endurance exercise thereby stimulating IGF-1 production [6]. Although this hormonal modulation could be one of the mechanisms by which exercise training exerts its beneficial effects on CHF patients, there are few data on endogenous exercise-mediated increase of anabolic hormones in such patients [7,8]. In particular there are no studies evaluating the hormonal response to interval training in CHF.

⁎ Corresponding author at: Cardiovascular Research Unit, Department of Medical Sciences, IRCCS San Raffaele — Roma, via della Pisana 235, 00163 Roma, Italy. Tel.: +39 06 660581; fax: +39 06 66058274. E-mail address: [email protected] (G. Caminiti).

http://dx.doi.org/10.1016/j.ijcard.2014.08.040 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to compare the hormonal responses induced in CHF patients by two different protocols of exercise: interval training (IT) and continuous training (CT). Subjects participating in this study were recruited from the cardiac rehabilitation department at S. Raffaele IRCCS, Rome, Italy. Twenty male patients (median age: 62.4 ± 5 years), with mild to moderate CHF NYHA class II/III, were enrolled. All subjects had a previous diagnosis of symptomatic CHF of at least 6 months, stable clinical condition (no hospitalization in the last 3 months), reduced left ventricle ejection fraction (LVEF) b40%. The details of the design of the study have been previously discussed [9]. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by San Raffaele Ethics Committee. Shortly, patients after signing of informed consent were randomly assigned on 1:1 basis to perform respectively IT (10 patients) and CT (10 patients). The two training methods were designed to obtain a similar total training load in the same period. Patients in the IT group warmed-up for 9 min, before walking four 4-min intervals by 2–4 times at 75–80% of heart rate recovery (HRR), with active pauses of 3 min of walking at 45–50% of patients in the CT group walked continuously at a moderate training intensity, ~45–60% of HRR for 30–45 min. The training period lasted 12 weeks. Venous blood samples (10 ml) were collected after 12 h of fasting between 07.30 and 08.00, two days before starting the training program and two days after last session of exercise. Total and free testosterone, sex hormone binding globulin (SHBG), GH and IGF-1 were assessed. Results are expressed as median ± standard deviation (SD) or percentages where appropriate. Within-group changes in the reported variables were evaluated by the paired t-test or Wilcoxon signed rank test for nonnormally distributed variables. Between groups comparisons were performed by the unpaired t-test and Mann–Whitney rank sum test. As already showed, there was a similar increase of VO2 peak in the two groups [9]. At baseline patients of the two groups had similar levels of anabolic hormones (Table 1). At the end of the training program total testosterone increased in the IT compared to CT group (28.5% vs 11.1%; between groups, p = 0.09). Free testosterone had a greater increase in the IT than CT group (27.3% vs 6.4%; between groups, p = 0.03). GH increased significantly in both groups without between groups differences. IGF-1 levels had a greater increase in the IT compared to CT

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G. Caminiti et al. / International Journal of Cardiology 176 (2014) 1433–1434

Table 1 Hormonal changes observed in the IT and CT group after the training period. IT

Total testosterone, ng/ml Free testosterone, pg/ml SHBG, nmol/L GH, mU/ml IGF1, ng/ml

CT

Baseline

12 weeks

Baseline

12 weeks

4.2 12.5 65.7 1.1 68.2

5.4 15.9 52.0 5.3 84.0

4.5 12.4 70.3 1.5 67.7

5.0 13.2 66.5 3.8 75.5

± ± ± ± ±

0.5 3.3 20 0.3 11

± ± ± ± ±

1.8 3.4a,b 15a 1.3a 14a,b

± ± ± ± ±

2.2 2.0 18 0.6 19

± ± ± ± ±

2.5 5.3 13 0.9a 15

SHBG = sex hormone binding globulin; GH = growth hormone; IGF-1 = insulin-like growth factor 1. a Intragroup, p b 0.05. b Between group, p b 0.05.

group (23.5% vs 11.5%; between groups, p = 0.03). SHBG decreased in both groups without between groups differences. In this study we observed a greater increase of total and free testosterone and IGF-1 after IT compared to CT in patients with CHF. This is the first study evaluating the effects of IT on serum levels of anabolic hormones in CHF. Our data suggest that the amount of hormonal response we observed after training was neither related to the improvement of exercise capacity nor to the total training load. IT and CT induced a similar significant improvement of VO2 peak in our population [9]. Moreover, these two training modalities were designed to obtain similar total training loads in the same period. On the contrary our results suggest that the amount of hormonal response is related to the exercise intensity. Similar results have been previously documented in healthy subjects in which the greater hormonal response has been ascribed to the higher mechanical and metabolic stimuli induced by IT [10]. In our study the levels of IGF-1 and testosterone did not change after CT. This observation is in agreement with the study of Kiilavuori et al. [7], performed on a similar population, in which only minor changes on testosterone, growth hormone and insulin emerged after a continuous physical training performed at 50–60% of the peak oxygen consumption.

In conclusion IT, by inducing a greater increase of anabolic hormones, may play a positive role in optimizing training adaptation particularly in those patients with CHF and anabolic/catabolic imbalance. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Anker SD, Chua TP, Ponikowski P, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure: the importance for cardiac cachexia. Circulation 1997;96:526–34. [2] Caminiti G, Volterrani M, Iellamo F, et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol 2009;54:919–27. [3] Cittadini A, Marra A, Arcopinto M, et al. Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency. JACC Heart Fail 2013;1:325–30. [4] Tremblay MS, Copeland JL, Van Helder W. Influence of exercise duration on postexercise steroid hormone responses in trained males. European Journal of Applied Physiology 2005;94:505–13. [5] Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Medicine 2005;35:339–61. [6] Nishida Y, Matsubara T, Tobina T, et al. Effect of low-intensity aerobic exercise on insulin-like growth factor-I and insulin-like growth factor-binding proteins in healthy men. Int J Endocr 2010;8 [Article ID 45282]. [7] Kiilavuori K, Naveri H, Leinonen H, Harkoven M. The effect of physical training on hormonal status and exertional hormonal response in patients with chronic congestive heart failure. Eur Heart J 1999 Mar;20:456–64. [8] Feiereisen P, Vaillant M, Gilson G, Delagardelle C. Effects of different training modalities on circulating anabolic/catabolic markers in chronic heart failure. J Cardiopulm Rehabil Prev 2013;33:303–8. [9] Iellamo F, Manzi V, Caminiti G, et al. Matched dose interval and continuous exercise training induce similar cardiorespiratory and metabolic adaptations in patients with heart failure. Int J Cradiol 2013;167:2561–5. [10] Hackney AC, Hosick KP, Myer A, Rubin DA, Battaglini CL. Testosterone responses to intensive interval versus steady-state endurance exercise. J Endocrinol Invest 2012;35:947–50.

Anabolic hormonal response to different exercise training intensities in men with chronic heart failure.

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