Short-term aerobic training improves heart rate variability in men living with HIV: a pre-post pilot study

Abstract

Background

Heart rate variability (HRV) a feasible predictor of prognosis in cardiovascular outcomes shown to be reduced in people living with HIV (PLWH).

Objective

This study sought to understand the effects of short-term aerobic training (AT) on the resting HRV and endothelial function in this population.

Methods

PLWH performed 24 sessions of AT protocol. The protocol consists of 40 min of treadmill (60 to 80% of the VO_2max), 3 times per week, for 8 weeks. HRV (standard deviation of all normal RR intervals - SDNN; root mean square of the successive differences - rMSSD; low frequency - LF; high frequency - HF; LF:HF ratio) and endothelial function parameters were evaluated by EndoPAT system pre and post intervention.

Results

7 men, the median age of the sample was 49 years (range, 38–68 years), completed the protocol. AT improved resting HRV parameters: SDNN (p = 0.02, power analysis (PA) 0.54), rMSSD (p = 0.02, PA = 0.99), LF (p = 0.02, PA = 0.85). HF, LF:HF ratio and endothelial function parameters showed no changes.

Conclusions

The results suggest the short-term AT may improve HRV in men living with HIV.

Keywords:

• Heart rate variability
• people living with HIV
• aerobic training
• autonomic nervous system
• endothelial function

Introduction

The autonomic nervous system (ANS) plays a key role in cardiovascular homeostasis and may be regarded as a strong predictor of prognosis in cardiovascular outcomes.^1–3 In clinical studies, the ANS is often evaluated according to heart rate variability (HRV), which may be assessed using several methods. Among time domain measures, the root mean square of successive differences (rMSSD) is an indicator of parasympathetic activity, while standard deviation of all normal RR intervals (SDNN) reflects sympathetic and parasympathetic activity. In the frequency domain, low frequency (LF) reflects sympathetic and parasympathetic activity, and high frequency (HF) and LF: HF ratio are indicators of parasympathetic activity.^1,3 Thus, a decrease in HRV is indicative of vagal control impairment and alteration(s) to sympathovagal balance.⁴

Previous data have demonstrated that people living with human immunodeficiency virus (PLWH) undergoing antiretroviral therapy exhibit reduced HRV and endothelial dysfunction, which may be associated with the risk for cardiovascular disease (CVD) and mortality.^2,5–7 Furthermore, ANS dysfunction demonstrated a positive correlation between the level of physical activity and HRV,³ suggesting that PLWH could benefit from improved fitness. As such, aerobic training (AT) has been used to improve physical fitness⁸ and parasympathetic and sympathetic activity in different populations.^3,9–11 However, the effects of AT on HRV remain inconclusive in PLWH undergoing antiretroviral therapy. Accordingly, the aim of the present study was to evaluate the effects of short-term AT on resting HRV and endothelial function in PLWH.

Material and methods

Subjects

This pre-post pilot study was conducted with PLWH 18–75 years of age, who were recruited at the Department of Infectious Diseases of the Irmandade da Santa Casa de Misericórdia de Porto Alegre, Rio Grande do Sul, Brazil. The study was approved by the Ethics Committee of the Universidade Federal de Ciências da Saúde de Porto Alegre (n° 797.649/14). Participants had a confirmed diagnosis of HIV infection, a viral load < 50 copies/mL, and were > 18 years of age. Exclusion criteria and study losses are shown in Figure 1. All patients provided informed written consent to participate before data collection.

Figure 1 Flow diagram of PLWH selection for participation in the aerobic training program. *Co-infection with hepatitis C virus (n = 86), hepatitis B virus (n = 7), diagnosed with psychological disorders (n = 6), cardiac abnormalities (n = 6), absence of ARV adherence (n = 6), human T-lymphotropic virus (n = 5), motor changes (n = 5), pregnancy (n = 3), Chagas disease (n = 2), cognitive impairment (n = 2), severe anemia (n = 2) illicit drug use (n = 1),visually impaired (n = 1) and 30 people living with HIV had 2 or more of these associated changes. ^#Abandoned training (n = 4), muscle injures (n = 2), cancer diagnosis (n = 1) and drug treatment failure (n = 1).

Anthropometric and clinical data

Body mass (kg), height (meters) and abdominal circumference were measured in the first and final training session. Fasting blood glucose, total cholesterol, triglycerides, HDL-C, LDL-C, T CD4 and viral load were collected from patient’s medical records before and after training protocol.

Cardiopulmonary exercise testing

Cardiopulmonary exercise testing (CPX) was performed using an electric treadmill (Centurion 300, Micromed Biotecnologia, Brasilia, Brazil). The ramp protocol was started at 3 km/h and 0% slope, and both treadmill speed and slope were increased gradually until participant exhaustion. The workload test was designed to obtain maximal oxygen uptake (VO_2max) within 8–12 min. The test was concluded when the peak respiratory exchange ratio was > 1.1 and VO₂ plateau was reached, even with increasing workload or request of the participant.¹² Ventilatory and metabolic parameters were collected by respiration using a spiro-ergometry system (Metalyzer 3B, Cortex Biophysik GmbH, Leipzig, Germany). The average of data points collected during the final 30 s of the test were used to determine peak oxygen uptake (VO_2peak) and maximal heart rate (HR_max). CPX was applied pre-intervention, and at 12 and after the 24 exercise training sessions.

HRV and endothelial function

HRV and endothelial function were evaluated using a pulse tonometry device (EndoPAT2000, Itamar Medical, Caesarea, Israel). For both tests, a blood pressure cuff is placed on one upper arm, while the contralateral arm serves as the control. After a 5 min equilibration period, the cuff is inflated to a pressure of 50 mmHg above systolic pressure or 200 mmHg for 5 min, and then deflated to induce a reactive hyperemia.¹³

Digital pulse amplitude was measured by placing a sensor on the tip of both index fingers with the patient supine. HRV parameters were calculated from the beat-by-beat HR time series over a duration of 10 min. The amplitude of the pulse response was recorded electronically in both index fingers and digitally analyzed using the computerized system (Itamar Medical, Caesarea Israel). SDNN and rMSSD were measured in the time-domain HRV, while LF, HF, and LF:HF ratio were calculated in the frequency-domain, HRV. The accuracy of HRV assessment according to EndoPAT 2000 was previously validated by Linder et al.,¹⁴ while endothelial function was evaluated according to the natural logarithm of the RH-PAT index (lnRHI) and augmentation index.

AT

Participants performed AT 3 times per week for a total of 24 sessions. Each session consisted of a 5 min warm-up, 30 min of exercise with load determined by CPX, and 5 min of cool-down.¹⁵ From the first to the 12^th session, exercise was performed at an HR corresponding to 60–65% of VO_2peak and, from the 13^th to the 24^th sessions, was increased to 75–80% of VO_2peak. Exercise intensity was adjusted in the 13^th session based on the new CPX.

Statistical analysis

Statistical analysis was performed using GraphPad Prism version 7 (GraphPad Inc, San Diego, CA, USA). Data are expressed as median (range). The Wilcoxon matched-pairs signed rank test was used to compare baseline and post-test values. Differences with p ≤ 0.05 were considered to be statistically significant. Effect size (ES) and study power analysis (PA) were calculated using G*Power version 3.1.9.4.

Results

Fifteen patients were eligible to participate in the present study; however, only 7 men consented to and completed the AT protocol. The median age of the sample was 49 years (range, 38–68 years), the median time of diagnosis and medication use was 93 (range, 12–182) and 93 (range, 10–180) months, respectively.

AT decreased body mass [74 (69.5–104.2) versus 71.7 (69–100.50) kg]; p = 0.02; abdominal circumference [98 (64–114) versus 94 (62–108) cm]; p = 0.02; fasting blood glucose [112 (88–128) versus 98 (86–116)] mg/dL; p = 0.02, total cholesterol [208 (178–340) versus 178 (152–228) mg/dL]; p = 0.03; triglycerides [273 (137–296) versus 204 (133–223) mg/dL]; p = 0.02; LDL-C [127 (89–252) versus 109 (85–154) mg/dL]; p = 0.02; and increased in VO_2peak [25 (16–45) versus 36 (28–43) ml.kg⁻¹.min⁻¹]; p = 0.03. All participants had undetectable viral load < 50 copies/mL.

AT increased SDNN (p = 0.02, ES = 0.96, PA = 0.54), rMSSD (p = 0.02, ES = 2.00, PA = 0.99), and LF (p = 0.02, ES = 1.41, PA = 0.85), while HF (ES = 0.91, PA = 0.50) and LF:HF ratio (ES = 0.07, PA = 0.05) demonstrated no changes. Both time and frequency-domain HRV parameters are shown in Figure 2. There was no significant change in the values of endothelial function (lnRHI = 1.26 [0.57–1.74] versus 1.28 [0.63–1.78]; p = 0.49) and augmentation index (5.50% [-4–14] versus 4% [-7–18]; p = 0.73).

Figure 2 Effects of aerobic training on heart rate variability in PLWH. (A) SDNN: standard deviation of normal sinus rhythm pulse intervals/ms; (B) RMSSD: root mean square of the successive differences/ms; (C) LF: low frequency; (D) HF: high frequency; (E) LF:HF ratio. Diamonds represent the average values. Circles and squares represent individual data before and after for aerobic training. Wilcoxon matched-pairs signed rank test was applied to compare baseline and post values. Statistical significance was defined as p ≤ 0.05.

Discussion

Results of the present study demonstrated that short-term AT may improve HRV in PLWH. The training protocol increased SDNN and rMSSD parameters, with a large ES.¹⁶ rMSSD and HF are indexes associated with the parasympathetic system, suggesting improvement in the ANS. Studies have suggested that reduced rMSSD is associated with risk factors for sudden death.^5,17 Because HIV infection increases the risk for CVD, including sudden cardiac death,⁵ is possible that the beneficial effects of AT on the ANS may decrease the risk for CVD.

Additionally, although HF was not significantly increased, is possible that a larger sample size may confirm the positive effect of AT on this particular marker. Thus, using the data obtained in this study (ES, 0.91; alpha error, 0.05), 13 subjects would be needed to reach a PA of 80%. Unfortunately, small sample sizes are typical in studies investigating the effects of exercise training in PLWH. A study involving PLWH did not find effects on HRV parameters after 16 weeks of concurrent training.¹⁰ The authors pointed out that the absence of exercise-induced effects could be explained by small sample size and, particularly, reduced volume (20 min) used in the AT program. As such, exercise volume (30 min), as well as the progressive intensity applied in the present study, are in accordance with exercise protocols that improved HRV.^11,18 Thus, moderate intensity AT, preferably >20 min per session, should be recommended to improve HRV in PLWH.

The decrease in HRV is associated with dysfunction of ANS cardiac markers and high risks for ventricular arrhythmias and mortality after acute myocardial infarction.¹⁶ Information regarding the extent to which AT is capable of affecting morbidity and mortality remains contradictory, largely due to alterations in cardiovascular function.^1,19 However, the benefits of AT for classic factors that contribute to CVD risk, such as lipid and glycemic alterations and sedentary lifestyle, have been well documented. Thus, the known benefits of AT for classic CVD risk factors in both healthy individuals and those with chronic diseases were supported by the results of this study.

In addition to improvement in classic CVD risk factors, we also observed a significant increase in VO_2peak, which demonstrated enhancement in the functional capacity of PLWH. A study reported a positive correlation between VO_2max and the time domain of HRV variables, indicating that AT promotes incremental improvement in HRV and demonstrated a positive association between VO_2max and parasympathetic tone.³ Although correlation analyses were not performed in this pilot study due to the small sample size, improvements in VO_2peak were, nevertheless, obtained, along with an increase in HRV variables, thus corroborating these results.

We did not observe an improvement in endothelial function. Conversely, a meta-analysis reported that exercise training—especially AT and/or combined—may improve endothelial function in patients with diabetes²⁰; however, differences were not statistically significant when compared to those in the control group.²⁰ Furthermore, it is important to note that, in PLWH, endothelial dysfunction may be associated with other deleterious factors, such as an inflammatory environment and viral load, thus supporting its characterization as a complex challenge.^6,7

Because this was a pilot study, results of the present investigation must be interpreted carefully. In addition to inferential tests, we included ES and PA to enhance the robustness of the data obtained. The complexity of factors underlying the health status of this particular patient population characterizes this as a complex intervention. The methods and protocol were, nevertheless, proven to be appropriate, although adherence to and acceptability of the protocol represent the primary challenges to implementation.

Results of the present study suggest that AT may improve HRV and the ANS, and decrease the influence of this system’s impairment on cardiac function in PLWH. Nevertheless, studies including a control group and a larger sample size(s) are needed to confirm our findings.

Disclosure statement

The are no relevant conflicts of interest to disclose.

Additional information

Funding

This study was funded by grants from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

Notes on contributors

Candissa Silva da Silva

Candissa Silva da Silva, PhD, is Physiotherapist at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil. She works with emphasis on the respiratory and motor rehabilitation of hospitalized patients. She has experience in the field of Physiotherapy, investigating, especially cardiopulmonary rehabilitation, respiratory physiotherapy and cardiovascular diseases.

Luís Fernando Deresz

Luís Fernando Deresz, PhD, is an Adjunct Professor of the Physical Education department, Post-Graduation Program in Sciences Applied to Health and Coordinator of the Research Group Science, Health and Physical Performance at the Universidade Federal de Juiz de Fora, Campus Governador Valadares. Governador Valadares, Brazil. He has experience in the field of physical education, with an emphasis on physical training in special populations, investigating, especially, the effects of physical training on cardiovascular risk.

Giovana de Marchi Castelli

Giovana de Marchi Castelli, Physiotherapist, acts as distance education analyst at support Program for Institutional Development of Support Program for Institutional Development of the Unified Health System (PROADI-SUS) at Hospital Moinhos de Vento, Porto Alegre, Brazil.

Gilson Pires Dorneles

Gilson Pires Dorneles, PhD, is a postdoctoral researcher at the Cellular and Molecular Immunology Laboratory at Universidade Federal de Ciências da Saúde de Porto Alegre linked to the Postgraduate Program in Health Sciences. His line of research comprises the following topics: exercise physiology and immunology, sports training, obesity, immune system, inflammatory processes, exercise prescription for individuals with chronic non-communicable degenerative diseases and cardiopulmonary evaluation.

Letícia Mignoni

Letícia Mignoni, is a Physiotherapist at UFCSPA, Porto Alegre, Brazil.

Pedro Dal Lago

Pedro Dal Lago, PhD, is an Associate Professor at Department of Physiotherapy, Post-Graduation Program in Health Sciences, Post-Graduation Program in Rehabilitation Sciences at Universidade Federal de Ciências da Saúde de Porto Alegre. His projects involving applied clinical research, bench and animal experimentation move into the area of translational research with a focus on pathophysiology and non-pharmacological resources applied to cardiorespiratory diseases. His line of research comprises the following topics: cardiopulmonary rehabilitation, respiratory physiotherapy, animal models of cardiovascular diseases, heart failure, physical exercise and inspiratory muscle training.