OBES SURG (2011) 21:1739–1749 DOI 10.1007/s11695-010-0319-4 CLINICAL RESEARCH Impact of Aerobic Exercise Training on Heart Rate Variability and Functional Capacity in Obese Women After Gastric Bypass Surgery Viviane Castello & Rodrigo Polaquini Simões & Daniela Bassi & Aparecida Maria Catai & Ross Arena & Audrey Borghi-Silva Published online: 20 November 2010 # Springer Science+Business Media, LLC 2010 Abstract Background Obesity is a major public health concern on a global scale. Bariatric surgery is among the treatment options, resulting in significant and sustainable weight loss as well as amelioration of comorbidities. The purpose of this study was to evaluate whether a 12-week aerobic exercise program positively impacts heart rate variability (HRV) and functional capacity after gastric bypass surgery (GBS) in a female cohort. Methods Of the 52 patients initially recruited, 21 were randomized to a training group (TG) or control group and successfully completed the study. Patients were tested on two occasions: 1 week before GBS and 4 months after GBS. Anthropometric variables, body composition, record of heart rate and R-R intervals, and 6-min walk test V. Castello : R. P. Simões : D. Bassi : A. M. Catai : A. Borghi-Silva (*) Cardiopulmonary Physiotherapy Laboratory, Nucleus of Research in Physical Exercise, Federal University of São Carlos, Rod. Washington Luis, km 235, 13565-905, São Carlos, São Paulo, Brazil e-mail: audrey@ufscar.br R. Arena Department of Internal Medicine, Virginia Commonwealth University Richmond, Richmond, VA, USA R. Arena Department of Physiology, Virginia Commonwealth University Richmond, Richmond, VA, USA R. Arena Department of Physical Therapy, Virginia Commonwealth University Richmond, Richmond, VA, USA (6MWT) were assessed at both time points. The TG underwent an aerobic exercise training program on a treadmill (1-h session, totaling 36 sessions over 12 weeks). Results The main findings from this study were: (1) only the TG demonstrated a significant increase (p<0.05) in all indexes of heart rate variability (HRV) after 12 weeks of aerobic exercise training and (2) only the TG demonstrated a significant increase (p<0.05) in 6MWT distance and decrease in diastolic blood pressure after aerobic exercise training. Conclusions We conclude that 12 weeks of aerobic exercise training improves cardiac autonomic modulation and functional capacity 4 months after GBS. Keywords Bariatric surgery . Autonomic nervous system . Morbid obesity . Severe obesity . Body mass index . Body composition . Physical fitness . Weight loss Introduction Obesity is considered one of the most serious public health concerns throughout the world [1]. Estimates from the World Health Organization [2] indicate that more than one billion adults are overweight and that 300 million in this cohort are clinically obese. Data from the Brazilian Institute of Geography and Statistics [3] indicate that 41.1% of men and 40% of women are overweight in this country. Moreover, obesity impacts 13% of the total Brazilian population with a higher rate among women (13.6%) compared with men (12.4%) [4]. The obesity epidemic is having a negative impact by increasing the risk of developing insulin resistance, type II diabetes, hypertension, dyslipidemia, sleep apnea syndrome, cardiovascular 1740 disease [5, 6], sympathetic nervous system alterations [7, 8], musculoskeletal complications, and certain forms of cancer [9]. In addition, obesity is often linked to a sedentary lifestyle pattern and is associated with reduced cardiorespiratory fitness [10]. Moreover, a reduced exercise capacity has been related to short-term complications after bariatric surgery [11]. Bariatric surgery is a surgical treatment option that results in significant and sustainable weight loss, leads to an improvement in comorbidity status, and may prevent many complications related to obesity [12]. In particular, gastric bypass surgery (GBS) has demonstrated favorable results both in terms of the extent and long-term maintenance of weight loss [13]. However, in a previous study [14] adherence to an exercise program was the sole significant behavioral predictor of weight loss following GBS. In addition, Maniscalco et al. [15] showed that 1 year after GBS, a significant increase in aerobic exercise capacity was associated with sustained weight loss. The relationship between improvement in aerobic fitness and weight loss was confirmed by Tompkins et al. [16], following morbidly obese patients 3 and 6 months after GBS. Poor aerobic fitness in morbidly obese patients is explained by both reduced cardiovascular function [10] as well as a low oxidative skeletal muscle capacity [17, 18]. In addition, reduced heart rate variability (HRV) is related to an increased body mass index (BMI) [19] and generally associated with increased morbidity and mortality in longitudinal studies [20]. On the other hand, 12 weeks of aerobic exercise training has significantly improved both the sympathetic and parasympathetic nervous activities in obese individuals [21] independent of weight loss. However, we are unaware of any previous study that has investigated the effects of a physical training program after GBS on HRV in morbidly obese patients. The purpose of this study is to therefore evaluate whether a 12-week aerobic exercise training program can modify HRV and functional capacity in severely obese women 4 months after GBS. We hypothesized that the application of aerobic exercise training will positively alter HRV in severely obese women after GBS. A secondary hypothesis is that the aerobic exercise training will result in an improvement in functional capacity. Materials and Methods Design and Study Population This is a prospective randomized controlled trial. Patients were recruited over a 2-year period (2007 to 2009) through the gastroenterologist physician overseeing the surgical procedure. All study assessments and the exercise training OBES SURG (2011) 21:1739–1749 program was performed in the Cardiopulmonary Physiotherapy Laboratory at Federal University of São Carlos. The present investigation included women with morbid obesity (BMI ≥40 kg/m2) [2] for more than 5 years, aged between 20 and 45 years who were undergoing a Roux-enY GBS. Exclusion criteria consisted of: (1) patients with orthopedic or neurological conditions that would preclude participation in an exercise program, (2) myocardial infarction (within 6 months of study enrollment), (3) implanted pacemaker, (4) unstable angina, (5) chronic disturbances in heart rhythm, (6) significant acute arrhythmias, (7) valvular heart disease, (8) a past history consistent with heart disease, (9) uncontrolled hypertension, (10) uncontrolled diabetes mellitus, (11) concomitant surgery, (12) chronic obstructive pulmonary disease, (13) betablocker use, (14) postmenopausal status, and (15) participation in a regular exercise program at the time of study enrollment. The investigation was approved by the Ethics Committee for Human Research of Institutions and all subjects signed a written consent form prior to the initiation of the study. Clinical Evaluation All patients underwent a clinical examination prior to surgery, which was performed by a gastroenterologist and a cardiologist. This examination consisted of a comprehensive medical history, resting 12-lead electrocardiogram (ECG), endoscopy and blood analysis used to determine hemoglobin, triglycerides, total cholesterol, and fractions: low-density lipoprotein (LDL) and high-density lipoprotein (HDL), fasting glucose, and uric acid. In addition, spirometric measurements, regular physical activity pattern, anthropometric data, record of heart rate (HR) and R-R intervals (R-Ri), and 6-min walk test (6MWT) were collected before gastric bypass surgery (BGBS) as detailed in the “Experimental Procedures” section. Surgical Procedure As previously indicated, all subjects in the present study underwent a Roux-en-Y GBS, which can be described as a combination of a restrictive and malabsorptive procedure. Through a midline incision supraumbilical, a small stomach pouch was first separated from the distal stomach; then, a Y-shaped section of the small intestine was connected to the gastric pouch to bypass the duodenum and a part of the jejunum. Finally, this bypassed portion of the intestine was attached more distally to the small bowel [22]. The patients were admitted to hospital on the morning of surgery, after a fasting period of 12 h, and the mean hospital stay was 3 days. Lastly, no subject in the present study had postoperative complications. OBES SURG (2011) 21:1739–1749 Experimental Procedures One month after GBS, the patients were randomized by using sequentially numbered, sealed, opaque envelopes into two groups: training group (TG) and control group (CG). All evaluations were made 1 week BGBS and 4 months after GBS (4GBS). Maximal exercise testing was applied 1 month after GBS to assist in prescribing an individualized exercise training program. All subjects were evaluated in the morning to avoid differing physiologic responses due to circadian changes and were instructed to avoid caffeinated and alcoholic beverages or any other stimulants the night before and the day of data collection. In addition, subjects were instructed to not perform activities requiring moderate-to-heavy physical exertion the day before the application of the protocols. All experiments were carried out in a climatically controlled room at 22–24°C and relative air humidity at 50–60%. 1741 b. Skinfold Thickness The skinfolds of the biceps, triceps, subscapular, suprailiac, abdomen, and thigh were measured thrice using metal calipers (Cescorf, Porto Alegre, Rio Grande do Sul, Brazil), and the average was used [27]. The analysis of percent of fat mass (FM%) and lean mass (LM) in kilograms was performed using four skinfolds (biceps, triceps, subscapular, and suprailiac), as suggested by Durnin and Womersley [28]. c. Body Circumferences We measured the circumferences of arm, axillary, xiphoid, hip, waist, and thigh using a flexible tape measure of 0.1 cm. Waist circumference was measured at the level of the umbilicus and the hips at the level of the iliac crest taken with the patient in a standing position. All measurements were performed thrice by research in Nutritional Sciences who had been previously trained and certified to perform these procedures, and the average was used [27]. Spirometric Measurements Record of HR and R-Ri The spirometric measurements were assessed to exclude individuals with airflow obstruction. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) assessments were performed using a spirometer (MedGraphics CPFS/D™ USB, St. Paul, MN, USA) with a calibrated pneumotachograph according to ATS standardization [23], and exclusion criteria was set at a FEV1/FVC <0.70 (GOLD) [24]. The values obtained were compared to the predicted normal values of Knudson et al. [25]. First, the subjects were maintained at rest in the supine position for approximately 10 min to ensure that a true resting HR value was obtained. Subsequently, the HR and R-Ri were recorded at rest in the supine position for 10 min with a cardiofrequencimeter (Polar S810i, Kempele, Oulu, Finland) fixed on the chest and with simultaneous transmission to the watch that stored the data; then, the data were transferred to a computer through an interface (Polar Advantage, Kempele, Oulu, Finland) for further analysis. Regular Physical Activity Pattern 6MWT Physical activity patterns were assessed by information regarding occupation, sports activities and leisure habits through the modified Baecke questionnaire for epidemiological studies [26]. This questionnaire consists of a scale of one to five (5 representing the most active) with eight questions pertaining to occupation, four addressing athletic activities, and four addressing habitual leisure habits. Results are reported as sum of scores (with minimum score of 4.5 and maximum 14.5). Anthropometric Variables and Body Composition a. Body Anthropometry Height and body weight were measured with women barefoot and light clothing to the nearest 1 mm and 0.1 kg, respectively, with an stadiometer (Welmy R-110, Santa Barbara do Oeste, São Paulo, Brazil). BMI was calculated by dividing the body weight in kilograms by the square of height in meters (kg/m2). Two tests were performed on alternating days, and the result of second 6MWT was considered for analysis [29]. The test was performed according to the recommendations of ATS [29], and the women were instructed to walk as fast as possible without running on a flat surface, 30 m long in 6 min. All subjects were given standardized encouragement during the test. Maximal dyspnea (assessed with the 0–10 Borg scale) [30] was obtained after the test, while HR and blood pressure (BP) were obtained immediately before and after 6MWT. Maximal Exercise Testing Maximal exercise testing was performed by a physician 1 month after GBS, to evaluate aerobic capacity and determine exercise training intensity. An incremental symptom-limited exercise test was performed on a treadmill (Imbramed master ATL, Porto Alegre, Rio Grande do Sul, 1742 Brazil) using the modified Bruce protocol [31]. Subjects were continuously monitored by ECG (Ecafix TC 500, São Paulo, São Paulo, Brazil). At the terminal portion of each stage of the exercise test, BP was measured by an indirect method, using a sphygmomanometer (BD, São Paulo, São Paulo, Brazil), HR was monitored by ECG and the Borg scale assessed subjective symptoms [30]. The termination criteria of the aerobic assessment followed AHA guidelines for exercise testing [32]. Physical Training Protocol Forty-eight hours following the maximal exercise test, the TG initiated the aerobic exercise training program on a treadmill. The sessions were held for 1 h on alternate days: three times per week, for 12 weeks, totaling 36 sessions. Each session consisted of: (1) initial 5 min of stretching the upper and lower limbs (hamstrings, quadriceps, calves, shoulders) and diaphragmatic breathing and awareness of proper posture in front of a mirror in the position standing and sitting, (2) 5 min of warm up on a treadmill at 3 km/h, (3) 40 min of exercise on treadmill with speed and inclination varying according to the behavior of HR; These 40 min were separated into four steps of 10 min each: step 1—intensity of exercise in which the HR remained at 50% of HR peak reached in maximal exercise testing, step 2— 60% of HR peak, step 3—70% of HR peak, and step 4— maintaining 70% of HR peak. (4) 1 min recovery at 3 km/ h and (5) 10 min of the same initial stretching and diaphragmatic breathing. HR and BP were obtained at the beginning of the session, at the end of each step, recovery, and at the end of the session. The sessions were performed individually and supervised by a physiotherapist. Following the 12-week aerobic exercise training protocol, the patients were re-evaluated (anthropometric data, record of HR and R-Ri, and 6MWT). Heart Rate Variability Analysis All artifacts were reviewed by visual inspection on the computer display. Only segments with >90% pure sinus beats were included in final analyses. The data were entered into Kubios HRV Analysis software (MATLAB, version 2 beta, Kuopio, Finland). HRV was analyzed with linear statistical measures in time-domain and with non-linear. Mean of HR, standard deviation of all N-N normal intervals (SDNN), square root of the difference in the sum of squares between R-Ri on the record, divided by the determined time minus one (RMSSD), number of R-Ri differing by more than 50 ms (NN50), and percentage of R-Ri differing by more than 50 ms (pNN50) were computed as time domain measures. In addition, non-linear statistical measures were calculated OBES SURG (2011) 21:1739–1749 by Poincaré plot perpendicular and along the line-ofidentity: standard deviation of instantaneous R-R interval variability (SD1) and standard deviation of long-term continuous R-Ri variability (SD2). Statistical Analysis The sample size was calculated using the GraphPad StatMate software, version 1.01. To reach statistical significance (p<0.05 at a power of 80% with a confidence interval of 95%), a sample of seven women was required in each group to demonstrate a mean difference between TG and CG. The mean difference to determine power according to HRV was 6 as derived from previous investigations [33]. Anticipating a dropout rate of 30%, we randomized a total of 32 patients. The Kolmogorov–Smirnov test was used to investigate the data distribution, and it confirmed that the distribution was normal. The data were then expressed as means and standard error (SE; for a 95% confidence interval). Fisher’s exact test for categorical data was compared with variables between two groups. The paired Student t test was used to compare the variables before and after 4 months following GBS and unpaired Student t test compared differences between the TG and CG. The gain obtained by the groups was derived from absolute delta comparisons (post-treatment minus pre-treatment), and p values <0.05 were considered significant. The analysis was carried out using the Statistica for Windows software release 5.1 (StatSoft, Inc, Tulsa, OK, USA) and Graphpad StateMade software release 1.01 (Inc, San Diego, USA). Results We recruited 52 women who were undergoing GBS; however, 15 were excluded due to uncontrolled hypertension (n=1), concomitant surgery (n=5), chronic obstructive pulmonary function (n=3), beta-blocker use (n=2), and musculoskeletal deficit (n=4). In addition, five patients did not consent to participate in the study. Thus, 32 women were considered eligible and were randomized to either the TG or CG (n=16, each group). However, only 11 of TG and ten of CG subjects successfully completed the study, as shown in Fig. 1. Three patients in the TG dropped out of the study due to trouble balancing work and the hours of physical training, and two did not like to exercise due muscle or joint pain. Furthermore, five patients of CG refused to participate in the reassessment (three lived in another city, which prevented re-evaluation, and two did not show interest in continuing the study due to lack of compliance) and one patient died secondary to cancer diagnosed post GBS. OBES SURG (2011) 21:1739–1749 1743 Fig. 1 Flowchart showing patient participation in the study n number of individuals, COPD chronic obstructive pulmonary disease, TG trained group, CG control group The initial evaluation demonstrated that the women presented with some degree of cardiac risk factors, both in the TG as in CG; however, there was no statistical difference between groups (Table 1). Furthermore, the use of prescription medications was not different between groups (Table 1). Spirometric Measurements As listed in Table 1, there were no significant differences between groups according to all indexes. However, the measured values were below predicted values in both groups. Regular Physical Activity Pattern On the basis of the Baecke questionnaire results, all women were considered to be sedentary with a total score at or below 8: 19 subjects had scores between 6 and 8, ten in the TG and nine in the CG; and two had scores below 6, one in each group [26]. In relation to patients who refused to continue in the study, (1) five of the training group were classified as sedentary and all had scores between 6 and 8 and (2) five in the control group were also classified as sedentary; however, three had scores between 6 and 8 and two had scores less than 6. Anthropometric Variables and Body Composition There were no significant differences between groups in BGBS with respect to anthropometry, skinfold thickness, and circumference. All patients lost weight 4 months post GBS, independent of participation in an exercise training program. However, when comparing BGBS with 4GBS within groups, there were no changes in abdominal and thigh skinfold thickness in the CG only. Additionally, subjects in the TG experienced a significant reduction in axillary, xiphoid, hip, waist, and thigh circumferences (Table 2). Delta of thigh circumference was comparable between groups to show the effects of the aerobic physical training (Fig. 2), and a significant reduction was observed only the TG. Heart Rate Variability HRV indexes are presented in Table 3. There were no significant differences between groups BGBS in relation to time domain and non-linear indexes. However, following GBS, there was a significant decrease in mean HR and increase of indexes SDNN, RMSSD, NN50, pNN50, SD1, and SD2 in the TG only. When comparing the TG and CG at 4GBS, only HR was comparable. Delta of effects of aerobic exercise training on SDNN and RMSSD index at rest were comparable between groups (Fig. 2), while only the TG demonstrated a significant improvement in indexes following the exercise intervention. 1744 OBES SURG (2011) 21:1739–1749 Table 1 Risk factors, medications, and lung function of patients before surgery Risk factors Anemia Diabetes Dyslipidemia Hypertension Hypothyroidism Smoking Medications Antidiabetic Angiotensin II receptor antagonist Angiotensin-converting enzyme inhibitors Calcium channel blocker Antidepressants Contraceptive Diuretics Data in lung function are presented as mean±SE. No differences were observed between groups TG trained group, CG control group, n number of individuals, FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, pred predict Table 2 Anthropometric data, skinfold thickness, and circumferences of patients (TG and CG) before and 4 months after surgery Data presented as mean±SE TG trained group, CG control group, n number of individuals, BGBS before gastric bypass surgery, 4GBS 4 months after gastric bypass surgery, BMI body mass index a Significant differences in relation BGBS (TG and CG; paired Student t test, p<0.05) b Significant differences between TG vs CG (unpaired Student t test, p<0.05) Thyroid-stimulating hormone (TSH) Lung function FVC (l) FVC (% pred) FEV1 (l) FEV1(% pred) FEV1/FVC FEV1/FVC (% pred) TG (n=11) CG (n=10) 2 0 1 3 2 2 1 1 1 2 1 1 1.0 0.47 1.0 1.0 1.0 1.0 0 1 1 1 4 5 3 1 1 1 0 3 3 2 0.47 1.0 1.0 1.0 1.0 0.65 1.0 2 1 1.0 3.3±0.2 94.1±3.2 2.7±0.2 91.9±4.7 79.3±3.9 93.6±4.6 3.2±0.2 92±3.6 2.8±0.2 94.5±3.6 84.9±1.8 101.9±1.9 0.95 0.66 0.58 0.66 0.20 0.11 TG (n=11) p value CG (n=10) Anthropometric data BGBS 4GBS BGBS 4GBS Age (years) Height (m) Weight (kg) BMI (kg/m2) Fat mass (%) Lean mass (kg) Skinfold thickness (cm) 38.0±4.0 1.59±0.02 117.0±4.0 45.64±1.51 45.8±1.4 63.0±3.4 – – 94.0±4.0a 36.82±1.28a 37.8±1.2a 58.0±2.9a 36.0±4.0 1.61±0.01 117.0±6.0 44.46±0.96 42.0±1.5 67.0±1.7 – – 94.0±5.0a 35.71±0.92a 36.0±1.1a 60.0±1.6a Biceps Triceps Subscapular Suprailiac Abdominal Thigh Circumferences (cm) Arm Axillary Xiphoid Hip Waist Thigh 3.9±0.6 5.2±0.4 5.2±0.6 4.4±0.4 6.2±0.4 7.0±0.4 42.3±1.1 113.6±1.6 108.8±2.6 129.8±2.7 124.3±2.8 79.0±2.7 2.1±0.2a 3.4±0.2a 3.0±0.3a 2.8±0.2a 3.9±0.3a 5.0±0.4a 36.1±1a 99.8±1.8a 93.7±1.7a 115.1±2.7a 105.2±2.2a 65.9±2a 3.0±0.4 4.2±0.5 4.0±0.5 3.7±0.5 6.2±0.5 5.9±0.5 40.8±0.8 113.6±2.9 108.5±3.2 131.5±3.2 123.1±3.6 75.7±1.9 1.9±0.2a 2.9±0.3a 2.5±0.3a 2.4±0.2a 4.7±0.6 4.7±0.7 37.9±0.8a 107.9±2.7ab 102.1±2.7ab 125.2±3.3ab 116.6±3.9ab 71.5±1.9ab OBES SURG (2011) 21:1739–1749 1745 Fig. 2 Delta of effects of the aerobic physical training in both groups. a SDNN: standard deviation of all N-N normal intervals. b RMSSD: square root of the difference in the sum of squares between R-R intervals on the record, divided by the determined time minus one. c Walking distance of 6-min walk test × delta of lean mass. d Circumference of thigh. Data presented as mean±SE. Single asterisk indicates the significant differences between trained group (TG; in gray) vs. control group (CG, in black), p<0.05 6MWT As listed in Table 3, there were no significant differences between groups at BGBS for all 6MWT variables. The aerobic exercise training protocol significantly increased walking distance, which was not observed in the CG. Systolic BP decreased significantly in both groups; however, only the TG significantly reduced diastolic BP after the aerobic exercise training program. Both groups significantly reduced perception of dyspnea Table 3 Variables of heart rate variability and 6MWT of patient’s (TG and CG) before and 4 months after surgery TG (n=11) Time-domain Mean HR (bpm) SDNN (ms) RMSSD (ms) NN50 (ms) pNN50 (%) Non-linear SD1 (ms) SD2 (ms) 6MWT Walking distance (m) HR (bpm) Systolic BP (mmHg) Diastolic BP (mmHg) Borg score (0–10) BGBS 74.1±2.4 29.2±5.0 30.2±5.2 31.3±13.5 10.5±4.5 CG (n=10) 4GBS 63.7±2.8a 58.9±10.7a 67±13.9a 105.4±24.6a 35.8±8.3a 21.5±3.7 52.1±8.3 477.9±22.9 128±1.7 170.5±5.2 90.5±4.0 5.8±0.9 BGBS 4GBS 76.4±2.5 23.0±5.0 24.1±6.7 23.7±15.6 8.0±5.3 69.3±3.1 27.9±4.5b 29.4±6.4b 31.4±10.7b 10.7±16.4b 47.9±9.9a 108.8±17.2a 17.2±4.8 38.8±7.6 20.9±4.6b 51.6±7.5b 527.6±17.7a 126.2±3.9 146.6±4.0a 85.0±3.0a 3.3±0.6a 492.6±21.1 128.3±5.5 171.0±7.1 92.0±2.4 5.0±0.8 509.0±12.5 127.5±5.5 150.0±7.1a 88.8±2.4 3.8±0.5a Data presented as mean±SE TG trained group, CG control group, n number of individuals, BGBS before gastric bypass surgery, 4GBS 4 month after gastric bypass surgery, HR heart rate, SDNN standard deviation of all N-N normal intervals, RMSSD square root of the difference in the sum of squares between R-R intervals on the record, divided by the determined time minus one, NN50 the number of R-R intervals differing by more than 50 ms, pNN50 (%) percentual of R-R intervals differing by more than 50 ms, SD1 standard deviation of instantaneous R-R interval variability, SD2 standard deviation of longterm continuous R-R interval variability, 6MWT 6-min walk test, BP blood pressure a Significant differences in relation BGBS (TG and CG; paired Student t test, p<0.05) b Significant differences between TG vs CG (unpaired Student t test, p<0.05) 1746 and leg exertion symptoms 4GBS, without any significant difference between groups. Figure 2 illustrates the delta of walking distance × delta of LM between TG and CG, and only the TG demonstrated a significant increase. In relation to patients who discontinued the study, we found that for the distance on the 6MWT of the five subjects in the TG, only one had a value lower than the observed mean. Conversely, three of five subjects in the CG were below the mean 6MWT distance. Discussion Summary of Findings The main findings from this study were: (1) only the TG showed a significant increase in all indexes of HRV after 12 weeks of aerobic exercise training, (2) only TG demonstrated a significant increase in 6MWT distance and decrease in diastolic BP after aerobic exercise training, and (3) GBS reduced weight and improved the symptoms of dyspnea, muscle fatigue, and reduced systolic BP and HR independent of aerobic exercise training. Importance of this Study and Methodological Considerations To our knowledge, this is the first study to evaluate the effects of aerobic exercise training after GBS on HRV in women with morbid obesity. Previous studies reported the effects of GBS and the benefits of an exercise program on physical fitness [5, 34], without assessment of cardiac autonomic control of HR. The effects of aerobic exercise training on the autonomic nervous system have been assessed in obese middle-age subjects who did not undergo GBS and significant improvement of sympathetic and parasympathetic nervous system were observed, suggesting a possible reversal effect of human autonomic nervous system dysfunction brought about by excess body weight and inactivity [21]. In relation to dropout rate, we believe that some of the participants refused to participate of study secondary to the observation that obese individuals have low adherence (60–70% dropout) to physical training programs as described by Dishman et al. [35]. Risk Factors, Medications, and Spirometric Measurements As listed in Table 1, there were no differences regarding risk factors, current medication, and spirometric variables between the TC and CG, suggesting that the groups were homogeneous after randomization. In relation to spiro- OBES SURG (2011) 21:1739–1749 metric variables, we used these measures to ensure exclusion of individuals with airflow obstruction (Fig. 1), as it is known that these individuals with this pulmonary condition have changes in autonomic cardiac function [36]. Regular Physical Activity Pattern The evaluation of the pattern of physical activity performed by Baecke questionnaire showed that all women had same level of physical activity at baseline and were classified as sedentary. This was also the case for women who refused to participate in the study, diminishing the possibility that “self-selection” could have affected the results. The level of physical activity is a factor of great importance for the comparative analysis of HRV, as physically active individuals have a better response of cardiac autonomic behavior as Sztajzel et al. [37] compared HRV of two trained athlete groups with one group of sedentary individuals and concluded that both trained groups had higher values of parasympathetic activity than the control group. Anthropometric Variables and Body Composition The decrease of weight, BMI, and FM% at 4GBS in relation to BGBS in both groups was expected, since the surgical procedure promotes weight loss due to caloric restriction and intestinal malabsorption [38]. Regarding LM, the reductions observed in both groups can be explained by high amount of weight loss, the malabsorptive characteristic of the procedure, and the inadequate protein intake inducing muscle atrophy [5, 39]. However, despite the aerobic exercise program implemented in the TG, the loss of muscle mass cannot be avoided, possibly due to the type of exercise applied (aerobic), which promotes greater improvement in muscle oxidative capacity than in muscle mass [5]. Regarding skinfold thickness, only abdominal and thigh skinfolds in CG did not improve from BGBS to 4GBS. Therefore, more marked reductions of these skinfolds in the group undergoing aerobic exercise training showed a greater effect of exercise on subcutaneous adipose tissue, particularly tissue in the lower limb muscles involved in the type of exercise (treadmill) implemented in the present study. This same explanation in relation to exercise with lower limbs can be considered in relation to arm circumference, which was the only variable that showed no difference between groups at 4GBS. Heart Rate Variability Regarding the CG, we did not find significant differences in both HR and HRV comparing BGBS to 4GBS, suggesting OBES SURG (2011) 21:1739–1749 that the surgical procedure itself resulted in no change in cardiac autonomic control. These results are not in agreement with the study of Alam et al. [40] that assessed the changes in HRV indexes 1, 6, and 12 months after bariatric surgery and found improvement of cardiac autonomic control 1 month following surgery. However, these patients underwent a different type of surgery in relation to our study (six patients underwent to laparoscopic gastric banding and five to bilio-pancreatic diversion), which may help to explain the difference in findings. Some studies suggest that improvement in HRV can be observed after reduction of at least 20% of body weight [40] or reductions greater than 28% in BMI [41]. In the current study, the reduction of body weight at the follow-up assessment was 19.6% for both groups and the decrease of BMI was 19.3% and 19.7% in TG and CG, respectively (data not showed); this finding may help to explain why HRV did not improve in the CG (i.e., level of weight loss was not high enough). However, longitudinal studies [33, 40–43] that assessed HRV between 6 and 12 months after different techniques of weight loss surgery found significant improvements in relation to these indexes. Therefore, the weight loss itself obtained by surgery seems to be effective in relation to cardiac autonomic control over the longer term, a time frame not incorporated into the current investigation. Both decrease in HR and increase in HRV observed in the TG (Table 3) suggest an improvement in cardiac autonomic control measured in these individuals, possibly provided by aerobic exercise training. However, the relationship between physical training and HRV in obesity has been controversial in some studies. Figueroa et al. [44] evaluated 28 obese women divided into two groups: with and without type 2 diabetes participating in 16 weeks of aerobic exercise training with subjects walking at 65% of peak oxygen consumption, 3 days/week at home and one supervised session on a treadmill in the laboratory. In this analysis, the authors did not observe changes in HRV after 16 weeks of training. In the study by Amano et al. [21] with obese individuals (without bariatric surgery procedure), the authors applied an aerobic exercise training program on a cycle ergometer (20 min at anaerobic threshold), three times/week for 12 consecutive weeks and demonstrated that HRV increased after exercise training, without significant weight loss. de Jong et al. [45] evaluated the impact of 6 months of caloric restriction on autonomic function in 48 overweight individuals, demonstrating the decrease in sympathetic nervous system and increase in parasympathetic nervous system function does occur with weight loss but is more pronounced when the caloric restriction is combined with exercise. These controversial findings in data might have been at least partially the result of different intensity, 1747 duration, and frequency of the implemented exercise training protocols as well as different subject characteristics (gender and age) in the various studies [46]. Our data support the hypothesis that the improvement in HRV was at least partially due to the aerobic exercise training program employed. Perugini et al. [47] demonstrated that HRV was inversely correlated with insulin resistance and directly correlated with the glucose disposition index, suggesting a correlation between hyperinsulinemia and poor HRV. Thus, the improvement of HRV after bariatric surgery found in previous studies appears to be linked to improvement of insulin resistance more so than the reduction in body weight. In this sense, we posit that physical exercise is an essential part of a rehabilitation program following GBS because it increases HDL cholesterol, lowers LDL cholesterol, and decreases insulin resistance, subsequently reducing the risk of cardiovascular disease [48]. Exercise therapy is a non-pharmacological treatment that improves HRV in myocardial infarction, chronic heart failure, and revascularization patients by increasing vagal tone and decreasing sympathetic activity [49]. In this context, the hypothesis is that a shift toward greater vagal modulation may also positively affect the prognosis of these individuals. The underlying mechanisms by which exercise training improves vagal modulation are speculative at present; however, it has been theorized that angiotensin II and nitric oxide may be potential mediators [49]. In this way, considering the risk factors and potential cardiac events that this population is exposed to, we believe that physical training should be an integral component of their care. 6MWT Previous studies have suggested the 6MWT can be used to develop an exercise program during the preoperative and postoperative phases of bariatric surgery [50], quantifying some aspects of functional capacity in obese patients and to monitor changes in physical fitness after an intervention. In our study, the walking distance increased after GBS only in the group undergoing the physical training program. For women who refused to participate in the study, individual values indicate that of five volunteers of training group, four were above mean, and three were below the mean in the control group, minimizing the possibility that the less fit people selectively dropped out of the study. Souza et al. [51] evaluated functional capacity using the 6MWT in severely obese subjects 1 day before and 7–12 months after Roux-en-Y gastric bypass surgery. The average distance walked in the postoperative phase was longer compared to the preoperative distance. Likewise, the study by Maniscalco et al. [15] showed that in 15 severely 1748 obese patients who underwent laparoscopic adjustable gastric banding, the distance walked during the 6MWT increased when compared with an assessment 1 year after the surgical procedure. In our study, two tests were performed because the first test tends to underestimate exercise capacity due to lack of familiarity with the subject’s test [29]. Moreover, we excluded patients with orthopedic or neurological conditions and cardiorespiratory complication, which may limit walking performance in obese. Thus, our findings show that a short period of 4 months after the GBS was unable to improve the functional capacity of women assessed by the 6MWT differently of group submitted to physical training. These findings demonstrate that the increased walking distance does not occur only in consequence of weight reduction, and that adherence to a training program can elicit positive changes in functional capacity after bariatric surgery. The present study also showed that the systolic BP decreased significantly after the GBS in both groups; however, only TG significantly reduced diastolic BP, possibly provided by aerobic exercise training. According to Lewington et al. [52], reductions of 10 and 5 mmHg in systolic and diastolic blood pressure, respectively, could decrease the long-term risk of death by ischemic heart diseases by about 40%. In our study, we observed a significant reduction of systolic BP (mean) after the GBS by approximately 24 mmHg for the TG and 21 mmHg in the CG, but in relation to diastolic BP the mean reduction was 5.5 mmHg in the TG and approximately 3 mmHg for the CG. This decrease in diastolic blood pressure is possibly due to a decrease in peripheral vascular resistance caused by improvement of vasodilatation of skeletal muscle after the aerobic exercise training program [53]. One limitation of the study was that the women included were not evaluated by ergospirometry to assess functional capacity or the prescription of physical training, a limitation that must be rectified by future investigations. In addition, further studies are needed to assess whether the improvement in autonomic function reduces cardiovascular morbidity and mortality in a population of severely obese women after bariatric surgery. Also, more information related to the behavior of HRV in trained and untrained individuals in the long term (i.e., ≥12 months post GBS) is needed. However, the current investigation is important in demonstrating only 4 months of physical training is a valuable non-pharmacological treatment in improving important physiologic variables such as HRV. We conclude that a 12-week aerobic exercise training program improves cardiac autonomic modulation and functional capacity in obese women 4 months after GBS. In this way, aerobic physical training can produce marked and faster benefits after GBS. OBES SURG (2011) 21:1739–1749 Acknowledgements The authors would like to thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-07/53202-9) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for providing both financial and material support. In addition, the authors also thank the medical gastroenterologists: Noé Carvalho Azambuja Jr and João do Nascimento Ortega. More importantly, however, the authors thank the patients for their effort and enthusiastic cooperation throughout the study. Conflict of Interest The authors declare that they have no conflict of interest related to the article or the research described. References 1. Wang Y, Beydoun MA. The obesity epidemic in the United States— gender, age, socioeconomic, racial/ethnic, and geographic characteristics: systematic review and meta-regression analysis. Epidemiol Rev. 2007;29:6–28. 2. World Health Organization (WHO). Obesity: preventing and managing the global epidemic: report of a WHO consultation. Geneva: World Health Organization; 2000. Technical report series no. 894. 3. Brazilian Institute of Geography and Statistics. Household Budget Survey 2002–2003. Available at: http://www.abeso.org.br (last accessed 20 April 2010). 4. Ministry of Health of Brazil. Vigitel Brazil 2008: monitoring of risk and protective factors for chronic diseases through telephone survey/Ministry of Health, Secretariat of Health Surveillance, Secretariat for Strategic and Participative Management. Brasilia, 2009. 5. Stegen S, Derave W, Calders P, et al. Physical fitness in morbidly obese patients: effect of gastric bypass surgery and exercise training. Obes Surg. 2009 [Epub ahead of print]. 6. National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med. 2000;160:898–904. 7. Bobbioni-Harsch E, Bongard O, Habicht F, et al. Relationship between sympathetic reactivity and body weight loss in morbidly obese subjects. Int J Obes. 2004;28:906–11. 8. Davy KP, Orr JS. Sympathetic nervous system behavior in human obesity. Neurosci Biobehav Rev. 2009;33:116–24. 9. Schelbert KB. Comorbidities of obesity. Prim Care Clin Off Pract. 2009;36:271–85. 10. Vanhecke TE, Franklin BA, Miller WM, et al. Cardiorespiratory fitness and sedentary lifestyle in the morbidly obese. Clin Cardiol. 2009;32:121–4. 11. McCullough PA, Gallagher MJ, Dejong AT, et al. Cardiorespiratory fitness and short-term complications after bariatric surgery. Chest. 2006;130:517–25. 12. Cowan Jr GS, Hiler ML, Buffington C. Criteria for selection of patients for bariatric surgery. Eur J Gastroenterol. 1999;11:69–75. 13. Jones Jr KB. Experience with Roux-en-Y gastric bypass, and commentary on current trends. Obes Surg. 2000;10:183–5. 14. Welch G, Wesolowski C, Piepul B, et al. Physical activity predicts weight loss following gastric bypass surgery: findings from a support group survey. Obes Surg. 2008;18:517–24. 15. Maniscalco M, Zedda A, Giardiello C, et al. Effect of bariatric surgery on the six-minute walk test in severe uncomplicated obesity. Obes Surg. 2006;16:836–41. 16. Tompkins J, Bosch PR, Chenowith R, et al. Changes in functional walking distance and health-related quality of life after gastric bypass surgery. Phys Ther. 2008;88:928–35. 17. Cortright RN, Sandhoff KM, Basilio JL, et al. Skeletal muscle fat oxidation is increased in African-American and white women OBES SURG (2011) 21:1739–1749 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. after 10 days of endurance exercise training. Obesity. 2006;14:1201–10. Privette JD, Hickner RC, Macdonald KG, et al. Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and white American women. Metabolism. 2003;52:735–8. Felber Dietrich D, Ackermann-Liebrich U, Schindler C, et al. Effect of physical activity on heart rate variability in normal weight, overweight and obese subjects: results from the SAPALDIA study. Eur J Appl Physiol. 2008;104:557–65. Bigger Jr JT, Fleiss JL, Rolnitzky LM, et al. Frequency domain measures of heart period variability to assess risk late after myocardial infarction. J Am Coll Cardiol. 1993;21:729–36. Amano M, Kanda T, Ue H, et al. Exercise training and autonomic nervous system activity in obese individuals. Med Sci Sports Exerc. 2001;33:1287–91. Bobbioni-Harsch E, Sztajzel J, Barthassat V, et al. The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass. Diabetologia. 2005;48:1258–63. American Thoracic Society. Standardisation of spirometry. Eur Respir J. 2005;26:1104–9. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of COPD. Am J Respir Crit Care Med. 2007;176:532–55. Knudson RJ, Lebowitz MD, Holberg CJ, et al. Changes in the normal maximal expiration flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127:725–34. Baecke JAH, Burema J, Frijters JER. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr. 1982;36:936–42. Bredella MA, Utz AL, Torriani M, et al. Anthropometry, CT, and DXA as predictors of GH deficiency in premenopausal women: ROC curve analysis. J Appl Physiol. 2009;106:418–22. Durnin JVG, Womersley P. Body fat assessed from total body density and its estimation from skinfold tickness: measurement in 481 men and women aged from 16 to 72 years. Br J Nutr. 1974;32:77–9. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002; 166:111–7. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377–81. Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J. 1973;85:546–62. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American college of cardiology/American heart association task force on practice guidelines (Committee to update the 1997 exercise testing guidelines). Circulation. 2002;106:1883–92. Nault I, Nadreau E, Paquet C, et al. Impact of bariatric surgeryinduced weight loss on heart rate variability. Metabolism. 2007;56:1425–30. Josbeno DA, Jakicic JM, Hergenroeder A, et al. Physical activity and physical function changes in obese individuals after gastric bypass surgery. Surg Obes Relat Dis. 2008;6:361–6. Dishman RK, Buckworth J. Increasing physical activity: a quantitative synthesis. Med Sci Sports Exerc. 1996;28:706–19. 1749 36. Reis MS, Arena R, Deus AP, et al. Deep breathing heart rate variability is associated with respiratory muscle weakness in patients with chronic obstructive pulmonary disease. Clinics. 2010;65:369–75. 37. Sztaizel J, Jung M, Sievert K, et al. Cardiac autonomic profile in different sports disciplines during all-day activity. J Sports Med Phys Fitness. 2008;48:495–501. 38. Zalesin KC, Franklin BA, Lillystone MA, et al. Differential loss of fat and lean mass in the morbidly obese after bariatric surgery. Metab Syndr Relat Disord. 2010;8:15–20. 39. Poitou BC, Ciangura C, Coupaye M, et al. Nutritional deficiency after gastric bypass: diagnosis, prevention and treatment. Diabet Metab. 2007;33:13–24. 40. Alam I, Lewis MJ, Lewis KE, et al. Influence of bariatric surgery on indices of cardiac autonomic control. Auton Neurosci. 2009;151:168–73. 41. Maser RE, Lenhard MJ, Irgau I, et al. Impact of surgically induced weight loss on cardiovascular autonomic function: one-year follow-up. Obesity. 2007;15:364–9. 42. Machado MB, Velasco IT, Scalabrini-Neto A. Gastric bypass and cardiac autonomic activity: influence of gender and age. Obes Surg. 2009;19:332–8. 43. Karason K, Mølgaard H, Wikstrand J, et al. Heart rate variability in obesity and the effect of weight loss. Am J Cardiol. 1999;83:1242–7. 44. Figueroa A, Baynard T, Fernhall B, et al. Endurance training improves post-exercise cardiac autonomic modulation in obese women with and without type 2 diabetes. Eur J Appl Physiol. 2007;100:437–44. 45. de Jong L, Moreira EA, Martin CK, et al. Team. Impact of 6month caloric restriction on autonomic nervous system activity in healthy, overweight, individuals. Obesity. 2010;18:414–6. 46. Hottenrott K, Hoos O, Esperer HD. Heart rate variability and physical exercise. Current status. Herz. 2006;31:544–52. 47. Perugini RA, Li Y, Rosenthal L, et al. Reduced heart rate variability correlates with insulin resistance but not with measures of obesity in population undergoing laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2010;6:237–41. 48. Kraus WE, Slentz CA. Exercise training, lipid regulation, and insulin action: a tangled web of cause and effect. Obesity. 2009;17:S21–6. 49. Routledge FS, Campbell TS, McFetridge-Durdle JA, et al. Improvements in heart rate variability with exercise therapy. Can J Cardiol. 2010;26:303–12. 50. Enright PL. The six-minute walk test. Respir Care. 2003;48:783– 5. 51. Souza SAF, Faintuch J, Fabris SM, et al. Six-minute walk test: functional capacity of severely obese before and after bariatric surgery. Surg Obes Relat Dis. 2009;5:540–3. 52. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13. 53. Pescatello LS, Franklin BA, Fagard R, et al. American college of sports medicine position stand. Exercise and hypertension. Med Sci Sports Exerc. 2004;36:533–53.