Effect of 12 Weeks Yoga Therapy on Heart  Rate Variability and Baroreflex Sensitivity  in Female Hypothyroid Patients:  A Randomised Control Trial

Abstract

Background

Thyroid hormones tend to regulate the metabolic rate of the body. The autonomic nervous system (ANS) is involved in the regulation of cardiovascular functions, and its dysfunction increases cardiovascular risk. About 65% of overt hypothyroid patients have autonomic dysfunction, which is due to sympathetic overactivity and parasympathetic withdrawal leading to a state of sympathovagal imbalance. Also, hypothyroidism is stated to be an independent risk factor for cardiovascular disease.

Purpose

Yoga practice helps in better modulation of the ANS and has been shown to improve autonomic function in diabetes and heart failure patients. Pranayama has been shown to improve cardiac autonomic function in hypothyroidism. Therefore, we aimed to assess the effect of three months of yoga therapy on autonomic functions in female hypothyroid patients on levothyroxine supplementation.

Methods

In this randomised open-label study, 99 hypothyroid women between the age groups of 18–50 years were recruited from the Endocrinology OPD in JIPMER and were randomly allocated to two groups. The study group subjects (n = 51) were administered three months of yoga therapy in addition to levothyroxine supplementation and a control group subjects (n = 48) received levothyroxine supplementation only. Autonomic function test parameters such as heart rate variability (HRV) and baroreflex sensitivity (BRS) were recorded at the baseline and after three months of study period in all the participants, and the parameters were compared between the groups and within the groups. HRV was measured from RR tachogram using Biopac MP150 and BRS was assessed using Finapres.

Results

After three months of yoga therapy in female hypothyroid patients on levothyroxine supplementation, HRV parameters showed a significant increase in parasympathetic tone (SDNN: p = .002, RMSSD: p = .021, NN50: p < .001, pNN50: p < .001, TP: p = .001, HF: p < .001, HFnu: p = .002) along with a decline in resting sympathetic activity (LF: p = .002, LFnu: p < .001, LF:HF ratio: p = .022) and a significant improvement in BRS (p < .001). Additionally, cardiovascular parameters also showed improvement in the yoga group (SBP: p < .001, DBP: p = .010, PP: p < .001, MAP: p < .001, RPP: p < .001) compared to the control group.

Conclusion

Three months of yoga practice in female hypothyroid patients in addition to routine levothyroxine therapy, it is effective in enhancing cardiac autonomic function with a shift towards parasympathetic predominance, and significant improvements in cardiovascular parameters. Yoga therapy may be suggested for hypothyroid patients to improve their cardiovascular health.

Keywords

Heart rate variability baroreflex sensitivity hypothyroidism yoga

Introduction

Hypothyroidism is one of the most common endocrine disorders, with females being affected more than males.¹ The thyroid hormone influences the autonomic function.² Autonomic dysfunction in hypothyroid patients is stated to be due to sympathetic overactivity and parasympathetic withdrawal, leading to a state of sympathovagal imbalance.³ Heart rate variability (HRV) analysis is a sensitive, extensively used, reproducible, easy to execute and non-invasive technique for the assessment of the autonomic function of the heart.⁴ Baroreflex sensitivity (BRS) is a sensitive tool for assessing the autonomic function of the cardiovascular system, including circulatory homeostasis.⁵ Treatment with levothyroxine in hypothyroidism does not completely restore cardiac autonomic function.⁶ This indicates the need for adjunct therapies in addition to hormone replacement.

Yoga therapy of 12 weeks duration is reported to increase parasympathetic activity and reduce sympathetic activity in cardiac failure patients.^{7, 8} Ranjana et al. reported improvement in metabolic and thyroid profile,⁹ and Akhtar et al.,¹⁰ observed improvement in quality of life following 6 months of yoga therapy in hypothyroid patients; however, they did not assess autonomic function. Pranayama for a one-month duration was shown to improve HRV in hypothyroid women; however, BRS was not assessed in this study.¹¹ Thus, there is a lack of studies on the combined effect of structured yoga therapy on HRV and BRS in levothyroxine-treated hypothyroid women. Therefore, this study was carried out to assess the effect of 12 weeks of structured yoga therapy on HRV and BRS in hypothyroid patients. This study was exclusively carried out in female hypothyroid patients due to the higher prevalence rate of hypothyroidism in women.¹²

Hypotheses: Twelve weeks of structured yoga therapy may have some significant effect on HRV and BRS in female hypothyroid patients on levothyroxine supplementation.

Materials and Methods

Design and Sample

This randomised open-label study was carried out in Jawaharlal Nehru Institute of Postgraduate Medical Education and Research (JIPMER), a tertiary care referral hospital in Puducherry, South India, during the period June 2018 to June 2020. The Institute ethics committee approval was obtained (JIP/IEC/2018/0272), and written informed consent was obtained from all participants before including them in the study. The study was registered in the Clinical Trial Registry of India (CTRI/2019/12/022482).

Sample Size Calculation

The required sample size was 49 in each group, calculated by comparing two independent means, using PS software version 3.1.2 and with 10% dropout, it was estimated to be 55. The sample size was estimated at 5% level of significance and 80% power, with a minimum expected difference in mean value of TP of HRV being 3.4 and a standard deviation of 6.

Subject Selection

Female hypothyroid individuals of the age group 18–50 years taking levothyroxine supplements, willing to undergo yoga therapy, attending the endocrinology outpatient department in JIPMER, and volunteering for the study were included. Known cases of diabetes mellitus, hypertension, heart diseases, autonomic dysfunction and those receiving chronic medication that could influence autonomic function, who were doing yoga practice or regular physical activity were excluded from the study. A simple random sampling technique was used. A computer-generated sequence was used for group allocation. Allocation concealment was maintained through the use of sequentially numbered, opaque, sealed envelopes, which were prepared by an independent researcher. The envelopes were opened after the baseline recording, and the group allocation was revealed to the patients. About 186 subjects were assessed for eligibility, of whom 110 individuals were randomized. The flow of participants at each stage of trail is shown in Figure 1. A total of 110 participants were randomised into two equal groups (n = 55 each). During the study period, four participants from the yoga group and seven from the control group dropped out due to personal reasons (e.g., relocation, lack of interest, or inability to attend follow-up visits). Therefore, the yoga group (n = 51) comprised those who underwent yoga therapy for 12 weeks in addition to levothyroxine supplementation, and the control group (n = 48) comprised those who were only on levothyroxine supplements. The overall dropout rate was 10%, which is considered minimal and was relatively balanced between the two groups, with no evidence of systematic attrition bias.

Statistical Analysis

The comparison of the continuous data between two groups was carried out by using an independent sample students t-test or Mann–Whitney U test, whichever was appropriate based on the distribution of data. Pre- and post-intervention in each group was carried out by using paired student’s t-test or Wilcoxon’s signed-rank test, whichever was appropriate based on the distribution of data. Statistical analysis was carried out at 5% level of significance, and p value <.05 was considered significant. Data entry was done in MS Excel 2013, and data analysis was carried out using IBM SPSS (Statistical Package for Social Sciences) version 22.0. A mixed- design ANOVA (2 × 2) was used to assess the effect of the intervention, with group (yoga vs. control) as the between-subject factor and time (pre vs. post) as the within-subject factor. Hedges’ g was calculated for post-intervention group comparisons to estimate the effect size.

Assessments

All assessments were performed by the principal investigator and were periodically supervised by the research guide. The recordings were obtained at around 9 am–10 am in a quiet environment. The study parameters were recorded twice (baseline and 3 months later) in both groups.

Recording of Anthropometric and BP Parameters

Height was measured using a stadiometer, and body weight was recorded with a bathroom scale. BMI was calculated using the formula BMI = Weight (kg)/[height (m)]².¹³ BP was measured using an automated BP monitor (AccuSure 1490-A). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and basal heart rate (BHR) were recorded using the instrument. Pulse pressure (PP) was calculated using the formula (PP = SBP-DBP).¹⁴ Mean arterial pressure was calculated using the formula: MAP = DBP + 1/3 of PP.¹⁴ Rate pressure product (RPP) was calculated using the formula: RPP = SBP × Heart rate × 10⁻².¹⁴

Recording of HRV

ECG recording was done for 10 minutes for short-term HRV analysis as per the standard procedure recommended by the Task Force on HRV.⁹ For the purpose, lead II ECG acquiring rate was 200 samples/second with the participant resting in supine position using the Biopac MP150 system. Transfer of the data was done from Biopac to a Windows-based PC that had AcqKnowledge software version 4.1. With the help of the R wave detector in the AcqKnowledge software, and the Kubios HRV analysis software, extraction of the RR tachogram was done from the 360 seconds of edited ECG segment that was carefully analysed for ectopics and artefacts. If present, they were carefully removed manually. The fixed R peak detector threshold was appropriately chosen for a successful retrieval of the RR interval. The RR interval data were analysed using HRV analysis software.

Recording of BRS

The Finapres (Finometer model-1, Finapres Medical Systems B.V., Amsterdam, The Netherlands) was used for the recording. The Finapres blood pressure cuff was tied around the mid-arm, and it was placed about 2 cm above the cubital fossa. Based on the finger width, the finger cuff of small, medium or large size was tied around the middle phalynx of the middle finger. For the height correction, one sensor was positioned at the heart level, and the other sensor was positioned at the finger level. After ten minutes of supine rest, the cables of the cuffs were connected to the Finometer, and the recordings were acquired. During the first five minutes of the recordings, the Physiocal and the return to flow calibration were carried out for the level correction between the brachial and finger pressure.¹⁵ Then, continuous BP was recorded for 10 minutes, and a PC-based data acquisition system (BeatScope Easy, Finapres Medical System B.V., Amsterdam) computed the parameters using the sequence method, which detects sequences of three or more consecutive heartbeats where SBP and RR intervals either increase or decrease in the same direction. The slope of the linear regression line fitting into these sequences was used to measure BRS.

Structured Yoga Intervention

The yoga protocol was designed specifically to improve autonomic balance in hypothyroid patients. It was validated by a certified yoga physician with over 10 years of clinical experience. The participants were trained in Advanced Centre for Yoga Therapy, Education and Research (ACYTER) by a qualified yoga trainer three times a week, each session lasting for 45 minutes for two weeks. Then the participants were asked to practice yoga at their home for a period of 12 weeks, a minimum of five times a week, which was cross-verified with their caregivers at home and through phone calls from the investigators. The participants were instructed to maintain a logbook, which was verified during their visit to OPD. The detailed yoga practice schedule is given in the following table.

Figure 1.

Schematic Representation of the Procedure Followed (Consort Flow Chart).

Baseline characteristics of patients who completed the study were compared between the two groups. During the 12-week study period, four participants from the yoga group and seven from the control group dropped out due to loss to follow-up, personal reasons, or lack of interest. The overall dropout from the study was 10% (dropout rate was 7.3% in the yoga group and 12.7% in the control group). A separate analysis for dropouts was not performed, as the dropout rate was low (10%). Both groups were comparable in terms of age, BMI, cardiovascular and HRV parameters at baseline (Table 1).

Table 1.

Comparison of Parameters Between Yoga Group and Control Group at Baseline.

Parameter	Yoga Group (n = 51)	Control Group (n = 48)	p Value
Demographic Details
Age (years)^$	38 (31–45)	40 (34–47)	.200
BMI	27.5 ± 25.80	27.29 ± 5.61	.842
Duration of hypothyroidism (years)^$	4 (2–7)	5 (2–8)	.274
Duration of levothyroxine use (years)^$	3.5 (2–6)	4 (2–7)	.318
Average levothyroxine dose (mcg/day)	75 ± 25	75 ± 25	1.000
Sleep < 6 hours/day, n (%)	21 (41.2%)	19 (39.6%)	.880
Cardiovascular Parameter
BHR (bpm)	71.99 ± 11.57	72.51 ± 12.98	.833
SBP (mm of Hg)	115.27 ± 10.95	115.31 ± 10.07	.986
DBP (mm of Hg)^$	72 (64–84)	76 (64–84)	.088
PP (mm of Hg)	41.71 ± 7.34	39.96 ± 6.55	.215
MAP (mm of Hg)	87.47 ± 7.00	88.67 ± 6.47	.378
RPP (mm of Hg/min)	83.23 ± 16.58	83.27 ± 14.94	.991
BRS (ms/mm of Hg)^$	8.19 (2–42)	9.35 (2.5–31)	.639
HRV Parameter
Mean RR (ms)	852.11 ± 28.11	831.52 ± 135.23	.439
SDNN (ms)	33.93 ± 19.90	33.93 ± 24.51	.999
RMSSD (ms)	42.22 ± 27.78	42.46 ± 37.78	.971
NN50 (beats)^$	38.00 (0–232)	36.50 (0–225)	.197
pNN50 (%)^$	11.26 (0–74.51)	9.46 (0–88)	.24
TP (ms²)^$	745.00 (30–10350)	614.00 (3–8663)	.397
LF (ms²)^$	248.50 (15–2679)	192.50 (2–3570)	.393
HF (ms²)^$	288.00 (14–7481)	348.00 (0–4863)	.627
LFnu	44.48 ± 18.65	44.21 ± 19.63	.943
HFnu	54.92 ± 18.89	53.81 ± 20.14	.778
LF: HF ratio^$	0.82 (0.11–6)	0.70 (0.149–6)	.847

Notes: The parametric data were presented as mean ± SD, and comparison of means was done by an independent t-test. The non-parametric data (^$) was expressed in median (Inter Quartile Range), and Mann–Whitney U test was used to compare between two groups. The p value <.05 was considered statistically significant. BMI: Body mass index; BHR: Basal heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; PP: Pulse pressure; MAP: Mean arterial pressure; RPP: Rate pressure product; BRS: Baroreflex sensitivity; SDNN: Standard deviation of normal to normal interval; RMSSD: The square root of the mean of the sum of the squares of the differences between adjacent NN intervals; NN50: Total pairs of adjacent RR intervals differing by more than 50 ms; pNN50: Percentage of NN50; TP: Total power; LF: Low-frequency power; HF: High-frequency power; LFnu: Normalised low-frequency power; HFnu: Normalised high-frequency power; LF-HF ratio: Ratio of low-frequency to high-frequency power; LF: Low-frequency power; HF: High-frequency power.

Within-group Analysis

After 12 weeks, when the pre- and post-values were compared (Table 2), there was a significant decrease in SBP (p < .001), DBP (p = .01), pulse pressure (PP) (p < .001), mean arterial pressure (MAP) (p < .001) and rate pressure product (RPP) (p < .001) in yoga group, whereas in the control group there was a significant increase in SBP (p < .001), PP (p < .001), MAP (p = .001) and RPP (p = .046). There was a significant increase in BRS in yoga group (p < .001).

Table 2.

Comparison of Parameters Before and After 12 Weeks in Yoga Group and Control Group.

Parameters	Yoga Group (n = 51)			Control Group (n = 48)
Parameters	Pre-test	Post-test	p Value	Pre-test	Post-test	p Value
Cardiovascular Parameters
BHR (bpm)	71.99 ± 11.57	71.43 ± 9.48	.559	72.51 ± 12.98	73.52 ± 10.50	.296
SBP (mm Hg)	115.27 ± 10.95	113.24 ± 9.99	<.001	115.31 ± 10.07	117.02 ± 10.46	<.001
DBP (mm Hg)^$	72 (64–84)	72 (64–82)	.010	76 (64–84)	76 (64–84)	.356
PP (mm Hg)	41.71 ± 7.34	39.98 ± 6.68	<.001	39.96 ± 6.55	41.38 ± 7.04	<.001
MAP (mm Hg)	87.47 ± 7.00	86.58 ± 6.47	<.001	88.67 ± 6.47	89.44 ± 6.58	.001
RPP (mm Hg/min)	83.23 ± 16.58	81.21 ± 14.80	<.001	83.27 ± 14.94	85.88 ± 13.03	.046
BRS (ms/mm Hg)^$	8.19 (2–42)	10 (3–45)	<.001	9.35 (2.5–31)	9.53 (2.97–32)	.055
HRV Parameters
Mean RR (ms)	852.11 ± 28.11	849.24 ± 128.36	.697	831.52 ± 135.23	820.19 ± 122.72	.187
SDNN (ms)	33.93 ± 19.90	35.65 ± 20.15	.002	33.93 ± 24.51	30.38 ± 15.93	.179
RMSSD (ms)	42.22 ± 27.78	43.36 ± 28.29	.021	42.46 ± 37.78	36.82 ± 21.21	.188
NN50 (beats)^$	38 (0–232)	40 (0.5–232)	<.001	36.50 (0–225)	36.50 (0–172)	.338
pNN50 (%)^$	11.26 (0–74.51)	13.33 (0.16–77.17)	<.001	9.46 (0–88)	9.46 (0–52)	.191
TP (ms²)^$	745 (30–10350)	750 (36–10320)	.001	614 (3–8663)	565.5 (9–8661)	.227
LF (ms²)^$	248.5 (15–2679)	248 (14–2679)	.002	192.5 (2–3570)	190 (2–3572)	.052
HF (ms²)^$	288 (14–7481)	377 (21–7481)	<.001	348 (0–4863)	334 (5–4863)	.194
LFnu	44.48 ± 18.65	43.93 ± 18.36	<.001	44.21 ± 19.63	45.65 ± 19.76	.045
HFnu	54.92 ± 18.89	58.76 ± 21.57	.002	53.81 ± 20.14	53.64 ± 20.51	.804
LF: HF ratio^$	0.82 (0.11–6)	0.74 (0.09–5.89)	.022	0.70 (0.15–6)	0.71 (0.15–6.58)	.002

Notes: The parametric data were presented as mean ± SD, and comparison of pre- and post-means was done by paired t-test. The non-parametric data (^$) was expressed in median (Inter Quartile Range) and the Wilcoxon Signed-Rank test was used to compare pre- and post-values. The p value <.05 was considered statistically significant. BHR: Basal heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; MAP: Mean arterial pressure; PP: Pulse pressure; RPP: Rate pressure product; BRS: Baroreflex sensitivity; SDNN: Standard deviation of normal to normal interval; RMSSD: The square root of the mean of the sum of the squares of the differences between adjacent NN intervals; NN50: Total pairs of adjacent RR intervals differing by more than 50 ms; pNN50: Percentage of NN50; TP: Total power; LF: Low-frequency power; HF: High-frequency power; LFnu: Normalised low-frequency power; HFnu: Normalised high-frequency power; LF-HF ratio: Ratio of low-frequency to high-frequency power.

The yoga group showed a significant increase from baseline in time domain indices of HRV such as SDNN (p = .002); RMSSD (p = .021); NN50 (p < .001) and pNN50 (p < .001), whereas no significant change was observed in control group. In the frequency domain indices of HRV, the yoga group showed a significant increase in total power of HRV (p = .001), HF (p < .001), HFnu (p = .002) and significant decrease in LF (p = .002); LF nu (p < .001) and LF: HF ratio (p = .022), whereas a significant increase in LFnu (p = .045) and LF: HF ratio (p = .002) was seen in control group. When the post-12-week values were compared (Table 3), the DBP (p = .024) and MAP (p = .032) were significantly less and pNN50 (p = .036) was significantly more in the yoga group than the control group. When the percentage changes from baseline were compared (Table 4), the yoga group showed a significant decrease in MHR (p = .048) and DBP (p = .018). In SBP, PP, MAP and RPP, the yoga group showed a decrease, whereas the control group showed an increase in percentage changes from baseline, and the differences were significant for SBP (p < .001), PP (p < .001), MAP (p < .001) and RPP (p < .001). In autonomic parameters, the yoga group showed a significant increase (p < .001) in mean RR, SDNN, RMSSD, NN50, pNN50, HF, HFnu and TP (p = .001) and a significant decrease (p < .001) in LF and LFnu in percentage changes from baseline compared to the control group. The percentage change from baseline in LF:HF ratio was decreased in yoga group, whereas it was increased in control group, and the difference was significant (p < .001).

Table 3.

Comparison of Parameters Post-12 Weeks in the Yoga Group and Control Group.

	Yoga Group (n = 51)	Control Group (n = 48)	p Value
Cardiovascular Parameters
BHR (bpm)	71.43 ± 9.48	73.52 ± 10.50	0.301
SBP (mm of Hg)	113.24 ± 9.99	117.02 ± 10.46	0.069
DBP (mm of Hg)$	72 (64–82)	76 (64–84)	0.024
PP (mm of Hg)	39.98 ± 6.68	41.38 ± 7.04	0.314
MAP (mm of Hg)	86.58 ± 6.47	89.44 ± 6.58	0.032
RPP (mm of Hg/min)	81.21 ± 14.80	85.88 ± 13.03	0.1
BRS (ms/mm of Hg)$	10 (3–45)	9.53 (2.97–32)	0.161
HRV Parameters
Mean RR (ms)	849.24 ± 128.36	820.19 ± 122.72	0.253
SDNN (ms)	35.65 ± 20.15	30.38 ± 15.93	0.154
RMSSD (ms)	43.36 ± 28.29	36.82 ± 21.21	0.198
NN50 (beats)$	40 (0.5–232)	36.50 (0–172)	0.124
pNN50 (%)$	13.33 (0.16–77.17)	9.46 (0–52)	0.036
TP (ms2)$	750 (36–10320)	565.5 (9–8661)	0.247
LF (ms2)$	248.5 (15–2679)	190 (2–3572)	0.368
HF (ms2)$	377 (21–7481)	334 (5–4863)	0.383
LF (nu)	43.93 ± 18.36	45.65 ± 19.76	0.655
HF (nu)	58.76 ± 21.57	53.64 ± 20.51	0.229
LF: HF ratio$	0.74 (0.09–5.89)	0.71 (0.15–6.58)	0.556

Notes: The parametric data were presented as mean ± SD and comparison of means was done by an independent t-test. The non-parametric data (^$) was expressed in median (Inter Quartile Range) and Mann–Whitney U test was used to compare between two groups. The p value <.05 was considered statistically significant. BHR: Basal heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; PP: Pulse pressure; MAP: Mean arterial pressure; RPP: Rate pressure product; BRS: Baroreflex sensitivity; SDNN: Standard deviation of normal to normal interval; RMSSD: The square root of the mean of the sum of the squares of the differences between adjacent NN intervals; NN50: Total pairs of adjacent RR intervals differing by more than 50 ms; pNN50: Percentage of NN50; TP: Total power; LF: Low-frequency power; HF: High-frequency power; LFnu: Normalised low-frequency power; HFnu: Normalised high-frequency power; LF-HF ratio: Ratio of low-frequency to high-frequency power.

Table 4.

Comparison of Percentage of Change in Parameters Post-12 Weeks in Yoga Group and Control Group.

	Yoga Group (n = 51)	Control Group (n = 48)	p Value
Cardiovascular Parameters
BHR (bpm)^$	0.00 (–19.19 to 57.14)	0.00 (–5.62 to 136.07)	0.048
SBP (mm of Hg)	–1.70 ± 1.43	1.47 ± 1.18	<.000
DBP (mm of Hg)^$	0.00 (–5.00 to 0.00)	0.00 (–7.50 to 14.29)	0.018
PP (mm of Hg)^$	–4.00 (–13.51 to 4.35)	4.26 (–33.33 to 25.00)	<.001
MAP (mm of Hg)^$	–0.80 (–4.17 to 0.68)	0.69 (–3.68 to 8.33)	<.001
RPP (mm of Hg/min)^$	–2.53 (–19.19 to 54.73)	1.55 (–3.90 to 139.59)	<.001
BRS (ms/mm of Hg)^$	14.29 (0.00–133.33)	0 (–11.11 to 60.00)	<.001
HRV Parameters
Mean RR (ms)^$	0.30 (–36.55 to 17.88)	0 (–29.96 to 1.18)	<.001
SDNN (ms)^$	4.82 (–58.64 to 70.85)	0 (–81.82 to 16.00)	<.001
RMSSD (ms)^$	3.45(–58.93 to 49.19)	0 (–84.26 to 10.00)	<.001
NN50 (beats)^$	2.10 (–80.00 to 700.00)	0 (–80.00 to 700.00)	<.001
pNN50 (%)^$	20.37 (–79.04 to 925.64)	0 (–86.36 to 316.67)	<.001
TP (ms2)$	0.46 (–41.67 to 126.09)	0 (–84.95 to 200.00)	0.001
LF (ms2)^$	–0.55 (–9.09 to 12.50)	0 (–77.03 to 3.11)	<.001
HF (ms2)^$	1.45 (–38.78 to 60.32)	0 (–93.35 to 15.99)	<.001
LFnu^$	–0.55 (–9.09 to 12.50)	0 (–5.77 to 90.96)	<.001
HFnu^$	1.45 (–38.78 to 60.32)	0 (–48.02 to 9.64)	<.001
LF: HF ratio^$	–1.14 (–94.90 to 177.23)	0.85 (–89.82 to 261.90)	<.001

Notes: The parametric data were presented as mean ± SD, and comparison of means was done by an independent t-test. The non-parametric data (^$) was expressed in median (Inter Quartile Range), and Mann−Whitney U test was used to compare between two groups. The p value <.05 was considered statistically significant. BHR: Basal heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; MAP: Mean arterial pressure; PP: Pulse pressure; RPP: Rate pressure product; BRS: Baroreflex sensitivity; SDNN: Standard deviation of normal to normal interval; RMSSD: The square root of the mean of the sum of the squares of the differences between adjacent NN intervals; NN50: Total pairs of adjacent RR intervals differing by more than 50 ms; pNN50: Percentage of NN50; TP: Total power; LF: Low-frequency power; HF: High-frequency power; LFnu: Normalised low-frequency power; HFnu: Normalised high-frequency power; LF-HF ratio: Ratio of low-frequency to high-frequency power.

Group Effect, Time Effect and Interaction Effect on Autonomic Function Parameters

The yoga group showed a significant increase in time domain indices of HRV such as SDNN (p = .002), RMSSD (p = .013), and NN50 (p = .130), while no significant change was noted in the control group compared to baseline (Table 5). Also, in the frequency domain indices, a significant increase was observed in HFnu (p = .0058) and a decrease was observed in LFnu (p = .071) in the yoga group (Table 5).

Table 5.

Assessment of Group Effect, Time Effect, and Interaction Effect in Yoga Group and Control Group.

Parameter	Group F	Group p	Group η²	Time F	Time p	Time η²	Interaction F	Interaction p	Interaction η²	Post Hedges’ g
Mean RR (ms)	8.434	.005	0.08	0.129	.72	0.001	0.17	.681	0.002	0.132
SDNN (ms)	14.235	.0003	0.128	9.82	.0023	0.092	9.485	.0027	0.089	0.077
RMSSD (ms)	47.148	<.001	0.327	6.39	.013	0.062	4.465	.037	0.044	0.024
NN50 (beats)	7.131	.009	0.068	2.338	.13	0.024	0	.989	0	0.215
TP (ms²)	92.194	<.001	0.487	0.236	.628	0.002	1.987	.162	0.02	−0.056
LF (ms²)	143.404	<.001	0.597	1.278	.261	0.013	0.492	.485	0.005	−0.178
HF (ms²)	72.746	<.001	0.429	0.007	.933	0	2.714	.103	0.027	−0.05
LF nu	0.235	.629	0.003	3.357	.071	0.042	2.098	.152	0.027	−0.057
HF nu	2.065	.154	0.021	7.96	.0058	0.076	8.453	.0045	0.08	0.239
LF:HF Ratio	1.774	.186	0.018	0.165	.685	0.002	0.203	.654	0.002	−0.114
BRS (ms/mm Hg)	54.215	<.001	0.359	72.287	<.001	0.427	39.906	<.001	0.291	0.15

Notes: SDNN: Standard deviation of normal to normal interval; RMSSD: The square root of the mean of the sum of the squares of the differences between adjacent NN intervals; NN50: Total pairs of adjacent RR intervals differing by more than TP: Total power; LF: Low-frequency power; HF: High-frequency power; LFnu: Normalised low-frequency power; HFnu: Normalised high-frequency power; LF-HF ratio: Ratio of low-frequency to high-frequency power, BRS: Baroreflex sensitivity; F: F-statistic, used in ANOVA to test significance; p: p value, indicates whether the effect is statistically significant (p < .05); η²: Partial eta squared; a measure of effect size (small ≈ 0.01, medium ≈ 0.06, large ≥ 0.14); Group F/p/η²: Compare overall differences between yoga and control groups.

Time F/p/η²: Show if there was a change from pre to post across all participants.

Interaction F/p/η²: Test whether the change over time differs between the yoga and control groups. Post Hedges’ g: Effect size comparing post-test values of yoga and control group.

Component	Practice	Duration	Purpose/Rationale
I. Loosening	General joint and muscle movements	10 min	Reduce stiffness, Improve circulation, Prepares body for asanas
II. Asanas	Ardha Chakrasana, Marjariasana,  Bhujangasana, Shalabhasana, Savasana	15 min(3 min each)	Stimulate the thyroid region, Improve spinal  flexibility, Regulate autonomic tone through  movement synchronised with breathing
III. Pranayamas	Chandranadi, Bhramari, Anulom– Vilom, Sheetali	20 min(5 min each)	Enhance parasympathetic activity and reduce  sympathetic activity, Reduce stress, anxiety
Total duration	Integrated Yoga	45 min	Low to moderate intensity, designed specifically for hypothyroid patients to improve autonomic regulation

TP remained unchanged over time (p = .628), but between-group comparison shows a significantly higher TP in the yoga group compared to the control (p < .001). A similar trend was observed in HF (p < .001) in the yoga group. In this study, LF was lower (p < .001) in the yoga group, though no significant time effect was observed in either group (Table 5).

When the interaction effects were studied, the yoga group showed a significant improvement over time in SDNN (p = .0027), RMSSD (p = .037), HFnu (p = .0045), and BRS (p < .001), indicating the benefits of yoga compared to the control group (Table 5). Remarkable improvement was seen in BRS, which showed a highly significant group effect (p < .001), time effect (p < .001), and interaction effects (p < .001), with the large effect size (η² = 0.291) as shown in Table 5. This suggests improvement in BRS in the yoga group due to the intervention.

Post-intervention comparison (Hedges’ g) value of HFnu (g = 0.239), NN50 (g = 0.215), and BRS (g = 0.150) in the yoga group (Table 5), indicates clinical improvements in parasympathetic activity and cardiovascular regulation. Though the other parameters like LF, HF, and LF:HF ratio did not demonstrate time or interaction effects, they showed significant differences between the groups, suggesting a benefit in the yoga group throughout the entire study duration.

Discussion and Conclusion

The present work was carried out to assess the effect of 12 weeks of yoga therapy on autonomic functions in female hypothyroid patients on thyroid supplements. After 12 weeks of yoga intervention, there was a significant decrease in SBP (p < .001), DBP (p = .010), PP (p < .001) and MAP (p < .001). This indicates decreased sympathetic activity following yoga therapy as SBP, DBP and MAP are regulated by the sympathetic nervous system.¹⁶ When the percentage changes were compared, there was a significant decrease (p < .001) in SBP, PP and MAP and DBP (p = .018) in the yoga group compared to the control group. We had earlier reported a reduction of SBP, DBP, MAP and RPP in heart failure patients⁷ and prehypertensive subjects¹⁷ following 12 weeks of yoga therapy. Also, a reduction in BP following yoga practice was reported by Hegde et al. in diabetic patients¹⁸ and Cohen DL in prehypertensive and hypertensive subjects.¹⁹ RPP is calculated as SBP × HR × 10⁻², and it reflects myocardial workload and oxygen intake. Thus, higher RPP indicates increased myocardial work stress.²⁰ There was significant decrease in RPP (p < .001) following 12 weeks of yoga practice and there was a significant reduction (p < .001) in percentage changes in RPP in the yoga group compared to the control group, indicating the reduction in myocardial work load following yoga practice which can be particularly beneficial in hypothyroid patients who are at increased risk of cardiovascular dysfunction, as hypothyroidism is known to result in increased vascular resistance, impaired left ventricular function, and reduced cardiac output.²¹

Time domain indices of HRV, that is, mean RR, SDNN, RMSSD, NN50, and pNN50, represent resting parasympathetic activity, and an increase in these indices reflects increased cardiac vagal modulation.⁹ After 12 weeks, in the yoga group, there was a significant increase in SDNN (p = .002), RMSSD (p = .021), NN50 (p < .001), and pNN50 (p < .001), indicating an increase in parasympathetic tone. Thus, 12 weeks of yoga therapy appears to be effective in boosting the vagal drive to the heart in hypothyroid women. This was more apparent as pNN50 was significantly higher in the yoga group compared to control group after 12 weeks (p < .001). The TP represents the sum of parasympathetic and sympathetic powers, but it is a potent marker of resting parasympathetic tone.⁴ Following 12 weeks of structured yoga practice, there was a significant increase in HF (p < .001), HF nu (p = .002) and TP (p = .001), whereas there was no change in the control group. This highlights the improved vagal drive in the yoga group subjects, which can be attributed to the practice of yoga therapy. Enhanced parasympathetic tone is associated with better cardiovascular health, improved adaptation to stress and reduced risk of cardiovascular mortality.²² There was a decrease in LF (p = .002) and LF nu (p < .001) in the yoga group, whereas the LF nu increased (p = .045) in the control group. The LF and LF nu indicate resting sympathetic activity. This shows that the practice of yoga for 12 weeks had markedly attenuated the sympathetic tone in these women. Decrease in sympathetic drive is considered useful as it reduces the risk of hypertension, cardiac arrhythmias and cardiovascular dysfunction.²²

Thus, there was an improvement in vagal tone and attenuation in sympathetic tone following three months of yoga practice added to levothyroxine therapy. In this way, with the simultaneous alteration in sympathetic and vagal tone, there was a change in sympathovagal balance with the ratio tilting in favour of a stronger parasympathetic tone. This was evident from the LF: HF ratio, which is an indicator of sympathovagal balance. Thus, a reduction in the LF:HF ratio in the yoga group suggests a potential cardioprotective effect in the hypothyroid women due to yoga therapy.²² In a study conducted by Chintala et al., the effect of one-month of pranayama training in newly diagnosed hypothyroid patients of age group 18–30 was assessed, where significant reduction in TP, LFnu and LF:HF ratio, and improvement in RMSSD and HF nu in both pranayama and control groups were found; and the percentage change was higher in pranayama group than in control group.¹¹ Our findings are similar to those of Chintala et al. in the yoga group, whereas we observed an increase in LF nu and LF:HF ratio in the control group, which is contradictory to their report in the control group. This could be due to the fact that they had studied newly diagnosed hypothyroid women in whom standard medical treatment was given in the control group during the one-month period, and the thyroxine supplementation could have caused improvement in the sympathovagal balance in their control group. We have studied chronic hypothyroid patients who are on thyroxine supplementation for a minimum of one year, and the effect of the drug must have stabilised over this period. Therefore, the percentage changes were also less in our study compared to those of Chintala et al.

In the yoga group, there was a significant rise in BRS value (p < .001) from baseline after 12 weeks. Also, the percentage change in BRS was significantly higher in the yoga group compared to the control group (p < .001). Given the fact that BRS was similar between the groups at baseline, this increase in BRS could possibly be due to 12 weeks of yoga therapy in hypothyroid women. BRS has been reported as a marker of sympathovagal balance.²³ Moreover, a decrease in BRS has been established as a non-invasive marker of CV risk.²⁴ Thus, a significant increase in BRS in the study group following yoga therapy further confirms the restoration of sympathovagal balance, decreasing CV risk in these hypothyroid women.

To understand the group effect, time effect and interaction effect on autonomic function parameters, the mixed-design (2 × 2) ANOVA was performed, in which there was significant improvement in SDNN, RMSSD, HFnu, and BRS following yoga therapy. Also, BRS showed the strongest improvements (large effect sizes across all tests). However, HRV, mean HR and LF/HF ratio did not show any significant changes. Interaction effects showed that the yoga group improved more over time than the control group. Significant group-time interactions in SDNN, RMSSD, HF nu, and BRS suggest that yoga specifically enhances parasympathetic activity. BRS, a key marker of cardiovascular regulation, showed the strongest effects (η² = 0.291), indicating autonomic improvement likely mediated by breath control and relaxation practices in yoga. The increase in HF nu, along with reductions in mean heart rate, points to enhanced vagal tone. This aligns with prior studies that have highlighted yoga’s ability to shift sympathovagal balance towards parasympathetic dominance. Parameters like LF and LF/HF ratio did not show significant interaction effects, suggesting that yoga’s influence may be more prominent on vagal (parasympathetic) activity rather than sympathetic or mixed components.

Autonomic dysfunction has been linked to increased cardiovascular risk in various disease conditions, including diabetes, hypertension and hypothyroidism.^{20, 25, 26} The observed improvement in the function of the autonomic nervous system (ANS) in levothyroxine-treated hypothyroid women, reflected by enhanced parasympathetic tone and reduced sympathetic tone, contributes to better heart rate regulation and therefore may support reduced cardiovascular morbidity. Furthermore, the increase in BRS also signifies the improved autonomic stability in hypothyroid patients who underwent yoga therapy in addition to levothyroxine hormone replacement.

The limitations of the present study were that the tests, which could have helped in further understanding of autonomic function, like cardiac autonomic reactivity tests, echocardiography, and the biochemical markers of sympathetic activity, could not be carried out. Also, the study was carried out only among females.

The present study showed that the practice of 12 weeks of yoga therapy significantly improved autonomic function and BRS in hypothyroid females. However, larger cohort studies are required to establish the usefulness of yogic practice as an adjunct to conventional therapy in hypothyroid patients.

Abbreviations

ANS: Autonomic nervous system

BMI: Body mass index

BRS: Baroreflex sensitivity

CVD: Cardiovascular disease.

DBP: Diastolic blood pressure

HPA: Hypothalamic pituitary axis

HRV: Heart rate variability

HR: Heart rate

MAP: Mean arterial pressure

PNS: Parasympathetic nervous system

RPP: Rate pressure product

SBP: Systolic blood pressure

SNS: Sympathetic nervous system

Adverse Events

No adverse events were reported by participants in both groups throughout the study period.

Authors’ Contributions

All authors are accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Pravati Pal, Gopal Krushna Pal, Jayaprakash Sahoo, Nivedita Nanda were responsible for conceptualising the research and deciding on the methodology to be followed.

Jayabal Karthiga and Natarajan Kavitha were responsible for the acquisition of data, data analyses, interpretation and manuscript drafting.

Pravati Pal, Gopal Krushna Pal, Jayaprakash Sahoo and Nivedita Nanda were involved in critically reviewing it for important intellectual content. Overall mentorship and approval of the final version were done by Pravati Pal.

Data Availability Statement

The datasets generated during and/or analysed during the current study and full study protocol are/will be available upon request from the corresponding author.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is part of the postgraduate research project by Dr Karthiga J, funded by JIPMER, Puducherry, India.

ICJME Statement

The clinical trial was registered under the Clinical Trials Registry of India was done. CTRI registration number: CTRI/2019/12/022482.

The informed consent was obtained from all participants of the study. All methods were carried out in accordance with relevant guidelines and regulations.

Statement of Ethics

This randomised control trial was conducted after receiving approval from the JIPMER Postgraduate Research Monitoring Committee (PGRMC) and JIPMER Institutional Ethics Committee (IEC) for human studies (IEC approval number: JIP/IEC/2018/0272) dated 30/08/2018. Registration in the Clinical Trials Registry of India was done (CTRI/2019/12/022482).

ORCID iDs

Jayabal Karthiga

Pravati Pal

References

Chiovato

, Magri

and Carlé

Hypothyroidism in context: Where we’ve been and where we’re going. Adv Ther 2019; 36(S2): 47–58.

Foley

, McAllister

and Hasser

EM.

Thyroid status influences baroreflex function and autonomic contributions to arterial pressure and heart rate. Am J Physiol Heart Circ Physiol 2001; 280(5): H2061–H2068.

Karthik

, Pal

, Nanda

, . Sympathovagal imbalance in thyroid dysfunctions in females: Correlation with thyroid profile, heart rate and blood pressure. Indian J Physiol Pharmacol 2009; 53(3): 243–252.

Malik

and Camm

AJ.

Heart rate variability and clinical cardiology. Br Heart J 1994; 71(1): 3–6.

Parati

, Ochoa

, Lombardi

, . Assessment and management of blood-pressure variability. Nat Rev Cardiol 2013; 10(3): 143–155.

Celik

, Aytan

, Dursun

, . Heart rate variability and heart rate turbulence in hypothyroidism before and after treatment. Ann Noninvasive Electrocardiol 2011; 16(4): 344–350.

Krishna

, Pal

, G

K P

, . Effect of yoga therapy on heart rate, blood pressure and cardiac autonomic function in heart failure. J Clin Diagn Res 2014; 8(1): 14–16.

Gomes-Neto

, Rodrigues-Jr

, Silva-Jr

, . Effects of yoga in patients with chronic heart failure: A meta-analysis. Arq Bras Cardiol 2014;103(5):433–439.

Ranjna

, Rukamani

, Somnath

, . Effect of yoga on thyroid function tests and biochemical parameters in patients suffering from hypothyroidism. Int J Appl Ayurv Res 2019; 4(5): 502–512.

10.

Akhtar

Role of yoga in improving quality of life of hypothyroidism patients. Int J Adv Med 2019; 6: 341–345.

11.

Chintala

, Samudrala

and Hari

Effect of short term pranayama on heart rate variability in hypothyroidism. Int J Physiol Nutr Phys Educ 2018; 3: 897–900.

12.

Verma

, Chaudhary

, Singh

, . Hypothyroidism in metabolic syndrome. Ann Afr Med 2024; 23(4): 717–722.

13.

Weir

and Jan

BMI classification percentile and cut off points. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2025.

14.

DeMers

and Wachs

Physiology, mean arterial pressure. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2025.

15.

Imholz

, Wieling

, van Montfrans

, . Fifteen years experience with finger arterial pressure monitoring: Assessment of the technology. Cardiovasc Res 1998; 38(3): 605–616.

16.

Grassi

, Mark

and Esler

The sympathetic nervous system alterations in human hypertension. Circ Res 2015; 116(6): 976–990.

17.

Thiyagarajan

, Pal

, . Additional benefit of yoga to standard lifestyle modification on blood pressure in prehypertensive subjects: A randomized controlled study. Hypertens Res 2015; 38(1): 48–55.

18.

Hegde

, Adhikari

, Kotian

, . Effect of 3-month yoga on oxidative stress in type 2 diabetes with or without complications: A controlled clinical trial. Diabetes Care 2011; 34(10): 2208–2210.

19.

Cohen

, Bloedon

, Rothman

, . Iyengar yoga versus enhanced usual care on blood pressure in patients with prehypertension to stage I hypertension: A randomized controlled trial. Evid Based Complement Alternat Med 2011; 2011: 546428.

20.

Pal

, Pal

, Nanda

, . Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: Physiological perspectives. Future Cardiol 2013; 9(1): 53–69.

21.

Udovcic

, Pena

, Patham

, . Hypothyroidism and the heart. Methodist DeBakey Cardiovasc J 2017; 13(2): 55–59.

22.

Schaarup

, Bjerg

, Hansen

, . Cardiovascular autonomic dysfunction precedes cardiovascular disease and all-cause mortality: 11-year follow-up in the ADDITION-PRO study. Diabetes Obes Metab 2025;27(9):5147–5159.

23.

Laitinen

, Hartikainen

, Niskanen

, . Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects. Am J Physiol Heart Circ Physiol 1999; 276(4): H1245–H1252.

24.

La Rovere

MT.

Baroreflex sensitivity as a new marker for risk stratification. Z Kardiol 2000; 89(15): III44–III50.

25.

Kaze

, Fonarow

and Echouffo-Tcheugui

JB.

Cardiac autonomic dysfunction and risk of silent myocardial infarction among adults with type 2 diabetes. J Am Heart Assoc 2023; 12(20): e029814.

26.

Bogdan

, Ivan

, Apostol

, . Hypothyroidism and heart rate variability: Implications for cardiac autonomic regulation. Diagnostics 2024; 14(12): 1261.

Effect of 12 Weeks Yoga Therapy on Heart Rate Variability and Baroreflex Sensitivity in Female Hypothyroid Patients: A Randomised Control Trial

Abstract

Background

Purpose

Methods

Results

Conclusion

Keywords

Introduction

Materials and Methods

Design and Sample

Sample Size Calculation

Subject Selection

Statistical Analysis

Assessments

Recording of Anthropometric and BP Parameters

Recording of HRV

Recording of BRS

Structured Yoga Intervention

Schematic Representation of the Procedure Followed (Consort Flow Chart).

Comparison of Parameters Between Yoga Group and Control Group at Baseline.

Within-group Analysis

Comparison of Parameters Before and After 12 Weeks in Yoga Group and Control Group.

Comparison of Parameters Post-12 Weeks in the Yoga Group and Control Group.

Comparison of Percentage of Change in Parameters Post-12 Weeks in Yoga Group and Control Group.

Group Effect, Time Effect and Interaction Effect on Autonomic Function Parameters

Assessment of Group Effect, Time Effect, and Interaction Effect in Yoga Group and Control Group.

Discussion and Conclusion

Abbreviations

Adverse Events

Authors’ Contributions

Data Availability Statement

Footnotes

Declaration of Conflicting Interests

Funding

ICJME Statement

Statement of Ethics

ORCID iDs

References

Effect of 12 Weeks Yoga Therapy on Heart  Rate Variability and Baroreflex Sensitivity  in Female Hypothyroid Patients:  A Randomised Control Trial