ABSTRACT
Introduction:
Cardiovascular health is adversely affected by menopausal transition with reduced heart rate variability (HRV) as a manifest. Electrocardiogram (ECG) based 5 min HRV has worsening trend from premenopausal to postmenopausal stage, but age is the biggest confounder. We aimed to study 5 min HRV among age-matched sample population of premenopausal, perimenopausal and postmenopausal healthy women.
Methodology:
A cross-sectional field study was conducted on apparently healthy women of 40-55 years of age. STRAW+10 criteria were used to stratify reproductive health stage groups. Lead II ECG-based 5 min HRV (VarioWin HR software) was recorded in supine position using standard protocol. Meticulous age matching was used to create premenopausal, perimenopausal (early and late), and postmenopausal (early and late) subgroups. Various age-matched pairs of subgroups were compared for time domain, frequency domain, and geometric HRV parameters.
Results:
There was a lack of significant difference among premenopausal, perimenopausal and postmenopausal subgroups. Difference of HRV was small, insignificant without any general pattern in age matched pair of: premenopausal verses early perimenopausal group (n = 24 each); early perimenopausal verses late perimenopausal group (n = 20 each); late perimenopausal verses early postmenopausal group (n = 13 each); and early postmenopausal verses late postmenopausal group (n = 17 each).
Conclusion:
Middle aged healthy women revealed lack of difference of 5 min HRV parameters between premenopausal, perimenopausal or postmenopausal women after age-matching. This lack of association indicates age and other confounders as significant attribute for HRV than the reproductive health status of women, and its calls for further study for reinforcement and causality.
Keywords: Age, autonomic nervous system, heart rate variability, menopause, perimenopause, premenopause
Introduction
The transition across the perimenopausal period is a challenge for the midlife health of women many of whom seek family physicians’ care. Instead of the withdrawal of hormonal support, a heavy toll is taken on cardiac health.[1,2] Menopause is known to alter cardiac autonomic balance, which manifests as reduced heart rate variability (HRV)[3,4,5,6,7,8,9] that can be practiced even at the primary care level. HRV is beat-to-beat R-R interval variability and a good objective indication for cardiac autonomic balance. Menopause,[4] gender,[10] and age[11] are 3 significant determinants of HRV, wherein the higher the HRV better the cardiac health.
There are few studies relating menopause to reduced HRV,[3,4,5,6,7,8,9] but none from our population, while comparing groups stratified by menopause. Age was not considered in most HRV studies, and the whole strata of STRAW+10 was not studied. With this background, we studied HRV among subgroups of midlife women about STRAW+10 criteria[12] after age matching.
Methodology
Study permission
We sought initial permission from physiology department and get our research protocol prospectively approved from Institutional Review Board of our institution; IRB EC approval number 1280/2023, Dept approval 106/2023, dated 09/08/2023. It was registered prospectively in CTRI and participants were enrolled after getting written informed consent.
Study set-up
A cross-sectional study was carried out in the general population of 2 cities, and multiple groups were chosen from 5 different areas to make a heterogeneous sample. A field study was carried out in the aforementioned areas with convenient sampling.
Study participants
A convenience sample among the general population was used to select healthy midlife women. We included women aged 40–55 years, with or without menopause, ready to give written informed consent. We prospectively excluded participants with current random plasma glucose (RPG) ≥200 mg/dL, blood pressure in hypertensive range as per JNC 8 criteria, body mass index (BMI) ≥32.5, thyroid disorder (self-reported), current smoker, alcoholic, tobacco chewing, chronic infection, surgical menopause, history of cardiovascular disease or intervention, use of drug altering cardiac autonomic function, polycystic ovarian disease, and polycystic ovary syndrome. One participant was excluded post-hoc HRV due to an abnormal electrocardiogram (ECG). The numerical details are further given in Figure 1.
Figure 1.
Study flowchart for participants’ selection
Study groups
Based on Stages of Reproductive Aging Workshop (STRAW+10),[12] study participants were divided into 3 subgroups: Premenopausal, perimenopausal and postmenopausal. The detailed scheme of participants grouping is given in Figure 1.
Participant assessment
For each enrolled participant, an initial assessment was carried out for personal history, reproductive history, medical history, and physical activity. RPG was assessed by glucometer, and office blood pressure was measured by mercury sphygmomanometer in the supine position using JNC-8 criteria. Barefoot height was measured by a stadiometer, and weight was measured by a weighing scale to derive BMI. Ten-minute rest was given before accomplishing the HRV measurement.
Heart rate variability measurements
The HRV measurement instrument and protocol are the same as those used in our previous[13,14] HRV studies. Beat-to-beat variability in SA nodal discharge was recorded by ECG and was computed and analyzed by the software Variowin HR to determine the indices of HRV. Assessment of HRV was accomplished between 9.00 am and 12.00 noon in an isolated room at the given community setting. Participants were asked to refrain from coffee, tea, and cola drinks before the procedure. A supine 5-min lead II ECG for the analysis of beat-to-beat HRV was taken after supine rest for at least 5 min, while the subject was in the supine position and breathing freely. The ECG was recorded from the precordial leads and transferred online to a microcomputer for the analysis of HRV. Only stationary time series of approximately 5-min duration, free of arrhythmia and artifacts, were used.
Heart rate variability parameters
HRV was studied in detail concerning frequency domain, time domain, and Pointcaré plot parameters as we published previously[13,14] and are mentioned here.
Time-domain analysis of HRV parameters encompassed RR interval, standard deviation of all RR intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), standard deviation of successive differences (SDSD) and pNN50, which is the percentage of consecutive RR intervals that differ by >50 ms.
Frequency-domain analysis of HRV included the power of high-frequency (HF), (0.15–0.40 Hz); low-frequency (LF), (0.04–0.15 Hz); and very low-frequency, (below 0.04 Hz) power ranges. LF and HF were presented also in normalized units and as a ratio.
Poincare plot analysis consisted of SD1 and SD2, which are standard deviation of RR interval along major and minor axis, respectively. Scatter index is expressed as ratio of SD1 to SD2 reflecting the non-linear HRV.
Statistical analysis
We entered data in Excel and sorted it into groups and subgroups. Quantitative data was expressed as mean and SD, while categorical data was expressed as frequency or number. We used GraphPad InStat 3 software (demo version free software of GraphPad Software, Inc. California, USA) for statistical analysis. A parametric or non-parametric distribution was checked before selecting the test. Two groups were compared by the Mann–Whitney U-test or t-test for quantitative data, and 3 groups with quantitative data were compared by the ANOVA test. The Chi-square test was used to compare the distribution of categorical data. For each test, P < 0.05 was taken as statistical significance.
Results
Baseline data of premenopausal, perimenopausal, and postmenopausal study groups revealed significant differences in age group and BMI. Among confounders, Systolic BP was higher in the premenopausal and perimenopausal groups than postmenopausal. There was no statistically significant difference in HRV parameters among the 3 subgroups for frequency and time domain parameters, with no specific pattern of increasing or decreasing trend. Among geometric measures, SD2 differed significantly among groups while other parameters did not [Table 1].
Table 1.
Comparison of heart rate variability parameters in pre, peri and postmenopausal groups
| Parameters | Premenopause (n=41) | Perimenopause (n=51) | Postmenopause (n=41) | P |
|---|---|---|---|---|
| Age (years) | 42±2.15 | 44.78±3.60 | 50.80±3.38 | <0.001* |
| BMI (kg/m²) | 26.18±3.02 | 26.37±3.72 | 24.68±3.59 | 0.048* |
| SRPA | 7/34 | 8/33 | 5/36 | - |
| Menopause (in years) | - | - | 7.51±5.60 | - |
| Systolic BP (mmHg) | 120.83±10.99 | 122.31±9.96 | 116.24±12.41 | 0.031* |
| Diastolic BP (mmHg) | 74.93±7.04 | 74.94±7.42 | 71.39±7.92 | 0.44 |
| Random blood glucose (mg/dl) | 130.29±24.82 | 123.96±18.53 | 130.66±21.99 | 0.25 |
| Frequency domain HRV indices | ||||
| Heart rate (bpm) | 80.68±9.24 | 76.10±8.93 | 76.66±10.50 | 0.06 |
| VLF power (ms²/Hz) | 712.48±566.99 | 680.12±591.71 | 601.55±488.12 | 0.64 |
| LF power (ms²/Hz) | 405.15±261.60 | 536.04±419.28 | 269.36±167.82 | 0.32 |
| HF power (ms²/Hz) | 381.06±504.52 | 409.17±512.96 | 236.89±220.78 | 0.14 |
| Normal LF power | 0.58±0.18 | 0.61±0.15 | 0.57±0.18 | 0.48 |
| Normal HF power | 0.45±0.18 | 0.39±0.15 | 0.43±0.18 | 0.18 |
| Maximum LF (Hz) | 0.08±0.10 | 0.07±0.03 | 0.06±0.02 | 0.18 |
| Maximum HF (Hz) | 0.27±0.09 | 0.26±0.08 | 0.28±0.08 | 0.56 |
| LF/HF ratio | 1.79±1.56 | 2.09±1.48 | 1.98±1.80 | 0.69 |
| Time domain HRV indices | ||||
| R-R interval (ms) | 751.56±91.39 | 793.48±90.04 | 788.68±107.25 | 0.09 |
| SDNN (ms) | 31.58±11.95 | 33.73±14.49 | 28.60±11.00 | 0.15 |
| RMSSD (ms) | 26.53±17.02 | 27.41±15.51 | 23.45±15.18 | 0.48 |
| SDSD (ms) | 25.21±17.57 | 26.20±16.04 | 21.85±15.98 | 0.44 |
| NN50 count | 28.80±53.33 | 24.96±31.91 | 17.46±31.62 | 0.44 |
| pNN50 (%) | 7.73±13.36 | 7.47±9.85 | 5.05±9.36 | 0.47 |
| Geometric HRV indices | ||||
| SD1 | 16.01±9.81 | 16.89±11.46 | 14.84±10.26 | 0.65 |
| SD2 | 35.21±12.46 | 38.50±15.34 | 31.49±11.66 | 0.043* |
| Scatter index (SD1/SD2) | 0.45±0.19 | 0.42±0.13 | 0.47±0.26 | 0.53 |
| Mode (ms) | 743.32±91.00 | 789.32±90.71 | 784.11±105.17 | 0.53 |
| Triangular HRV Index | 8.36±2.98 | 7.90±2.38 | 6.97±2.36 | 0.48 |
*Indicates statistical significance. HRV=Heart rate variability, HF=High-frequency, LF=Low-frequency, BP=Blood pressure, BMI=Body mass index, VLF=Very low frequency, SRPA=Self-reported physical activity
We compared age-matched 24 premenopausal and postmenopausal participants. Most confounders were comparable except heart rate, which was significantly high in the premenopausal group. Most HRV parameters were increased in the perimenopausal than the premenopausal group, but statistical significance was evident only for LF power and mode value [Table 2].
Table 2.
Comparison of heart rate variability parameters in age matched premenopausal and early peri-menopausal groups (n=24 each)
| Parameter | Premenopause (n=24) | Early perimenopause (n=24) | P |
|---|---|---|---|
| Age (years) | 42.50±2.36 | 42.79±2.64 | 0.76 |
| BMI (kg/m²) | 25.68±2.78 | 27.14±3.70 | 0.13 |
| SRPA | 4/20 | 4/20 | - |
| Duration since menopause | - | - | - |
| Systolic BP (mmHg) | 122.67±11.03 | 122.63±10.32 | 0.98 |
| Diastolic BP (mmHg) | 76.17±7.56 | 74.88±8.49 | 0.58 |
| Random blood glucose (mg/dl) | 126.04±26.81 | 120.63±17.62 | 0.70 |
| Average R-R interval (ms) | 733.70±96.18 | 792.33±83.16 | 0.029* |
| Heart rate (bpm) | 82.50±10.12 | 76.00±8.17 | 0.018* |
| Frequency domain indices | |||
| VLF power (ms²/Hz) | 694.59±621.04 | 802.90±801.48 | 0.62 |
| LF power (ms²/Hz) | 377.49±236.58 | 663.87±520.10 | 0.035* |
| HF power (ms²/Hz) | 401.48±616.57 | 537.08±693.93 | 0.48 |
| Normal LF power | 0.57±0.19 | 0.61±0.15 | 0.45 |
| Normal HF power | 0.48±0.19 | 0.39±0.15 | 0.07 |
| Maximum LF (Hz) | 0.10±0.13 | 0.69±0.29 | 0.84 |
| Maximum HF (Hz) | 0.26±0.08 | 0.28±0.09 | 0.62 |
| LF/HF ratio | 1.62±1.18 | 2.11±1.67 | 0.29 |
| Time domain indices | |||
| SDNN (ms) | 31.07±12.62 | 37.75±18.26 | 0.19 |
| RMSSD (ms) | 26.85±19.79 | 32.14±19.10 | 0.17 |
| SDSD (ms) | 25.54±20.29 | 31.13±19.54 | 0.16 |
| NN50 count | 29.04±64.22 | 34.50±37.92 | 0.30 |
| pNN50 (%) | 7.55±15.44 | 10.49±11.80 | 0.24 |
| Geometric measures | |||
| SD1 | 16.50±11.50 | 19.87±14.97 | 0.28 |
| SD2 | 34.02±12.54 | 42.34±18.83 | 0.11 |
| Scatter index (SD1/SD2) | 0.48±0.23 | 0.46±0.16 | 0.95 |
| Mode (ms) | 728.63±99.94 | 787.36±81.73 | 0.031* |
| Triangular HRV index | 8.38±3.19 | 8.18±2.66 | 0.89 |
*Indicates statistical significance. HRV=Heart rate variability, HF=High-frequency, LF=Low-frequency, BP=Blood pressure, BMI=Body mass index, VLF=Very low frequency, SRPA=Self-reported physical activity
We compared 20 age-matched early perimenopausal and late perimenopausal participants, who were comparable for confounding parameters. The early perimenopausal group reveals higher HRV parameters than the latter group, of which only the scatter index was statistically significant [Table 3].
Table 3.
Comparison of heart rate variability parameters in age-matched early and late peri-menopausal groups (n=20 each)
| Parameter | Early perimenopause (n=20) | Late perimenopause (n=20) | P |
|---|---|---|---|
| Age (years) | 45.25±2.86 | 45.65±2.89 | 0.60 |
| BMI (kg/m²) | 27.38±2.91 | 25.76±3.22 | 0.10 |
| SRPA | 4/16 | 3/17 | - |
| Systolic BP (mmHg) | 123.25±9.92 | 122.30±9.29 | 0.76 |
| Diastolic BP (mmHg) | 74.20±8.56 | 75.60±5.84 | 0.55 |
| Random blood glucose (mg/dl) | 120.35±18.84 | 128.40±20.48 | 0.20 |
| Average R-R interval (ms) | 802.27±80.44 | 775.37±103.12 | 0.36 |
| Heart rate (bpm) | 75.05±7.72 | 78.15±10.33 | 0.29 |
| Frequency domain indices | |||
| VLF power (ms²/Hz) | 783.80±817.50 | 562.51±300.07 | 0.34 |
| LF power (ms²/Hz) | 570.63±473.63 | 398.75±335.01 | 0.40 |
| HF power (ms²/Hz) | 519.76±715.90 | 285.60±217.35 | 0.51 |
| Normal LF power | 0.59±0.15 | 0.62±0.16 | 0.48 |
| Normal HF power | 0.41±0.15 | 0.38±0.16 | 0.45 |
| Maximum LF (Hz) | 0.08±0.03 | 0.07±0.02 | 0.47 |
| Maximum HF (Hz) | 0.28±0.08 | 0.23±0.07 | 0.07 |
| LF/HF ratio | 1.82±1.24 | 2.17±1.37 | 0.40 |
| Time domain indices | |||
| SDNN (ms) | 36.66±18.21 | 28.62±8.17 | 0.18 |
| RMSSD (ms) | 32.47±20.40 | 21.10±8.46 | 0.06 |
| SDSD (ms) | 31.44±20.86 | 19.58±9.22 | 0.06 |
| NN50 count | 33.55±37.83 | 11.40±14.78 | 0.11 |
| pNN50 (%) | 10.32±11.82 | 3.20±4.10 | 0.09 |
| Geometric measures | |||
| SD1 | 20.43±16.25 | 13.16±5.44 | 0.12 |
| SD2 | 40.70±18.14 | 34.00±10.61 | 0.28 |
| Scatter index (SD1/SD2) | 0.47±0.16 | 0.38±0.10 | 0.046* |
| Mode (ms) | 798.06±78.94 | 771.66±104.75 | 0.37 |
| Triangular HRV index | 7.96±2.53 | 7.21±1.67 | 0.28 |
*Indicates statistical significance. HRV=Heart rate variability, HF=High-frequency, LF=Low-frequency, BP=Blood pressure, BMI=Body mass index, VLF=Very low frequency, SRPA=Self-reported physical activity
Thirteen age-matched late perimenopausal and early postmenopausal participants were compared, who had comparable confounders except increased systolic BP in late perimenopausal. Both groups did not have a significant difference in HRV parameters and exhibited no general pattern of high and low HRV [Table 4].
Table 4.
Comparison of heart rate variability parameters in age matched late peri-menopausal and early post-menopausal groups (n=13 each)
| Parameter | Late perimenopause (n=13) | Early postmenopause (n=13) | P |
|---|---|---|---|
| Age (years) | 47.38±1.90 | 48.08±1.60 | 0.33 |
| BMI (kg/m²) | 25.84±3.54 | 26.08±2.45 | 0.84 |
| SRPA | 4/20 | 4/20 | - |
| Systolic BP (mmHg) | 123.08±8.41 | 111.69±12.74 | 0.013* |
| Diastolic BP (mmHg) | 74.69±5.71 | 69.69±7.16 | 0.06 |
| Random blood glucose (mg/dl) | 125.38±22.92 | 129.92±21.64 | 0.61 |
| Avg. R-R interval (ms) | 789.37±107.10 | 761.36±130.43 | 0.56 |
| Heart rate (bpm) | 76.85±10.60 | 79.46±13.00 | 0.58 |
| Frequency domain indices | |||
| VLF power (ms²/Hz) | 513.78±275.72 | 565.04±274.86 | 0.64 |
| LF power (ms²/Hz) | 335.16±206.96 | 320.78±183.13 | 0.85 |
| HF power (ms²/Hz) | 280.17±265.19 | 268.64±283.32 | 0.92 |
| Normal LF power | 0.63±0.20 | 0.61±0.15 | 0.83 |
| Normal HF power | 0.38±0.20 | 0.39±0.15 | 0.81 |
| Maximum LF (Hz) | 0.07±0.03 | 0.06±0.02 | 0.34 |
| Maximum HF (Hz) | 0.23±0.08 | 0.25±0.09 | 0.92 |
| LF/HF ratio | 2.42±1.63 | 2.17±2.11 | 0.55 |
| Time domain indices | |||
| SDNN (ms) | 27.70±9.03 | 28.77±11.07 | 0.79 |
| RMSSD (ms) | 20.94±9.93 | 22.39±14.49 | 0.92 |
| SDSD (ms) | 19.30±10.87 | 20.64±15.41 | 0.80 |
| NN50 count | 12.08±16.98 | 20.46±32.75 | 0.84 |
| pNN50 (%) | 3.44±4.65 | 6.33±10.73 | 0.92 |
| Geometric measures | |||
| SD1 | 13.20±6.33 | 13.58±8.42 | >0.99 |
| SD2 | 32.62±11.22 | 32.11±11.69 | 0.91 |
| Scatter index (SD1/SD2) | 0.39±0.12 | 0.41±0.13 | 0.73 |
| Mode (ms) | 786.29±110.09 | 761.94±124.01 | 0.60 |
| Triangular HRV index | 6.95±1.91 | 7.10±2.50 | 0.87 |
*Indicates statistical significance. HRV=Heart rate variability, HF=High-frequency, LF=Low-frequency, BP=Blood pressure, BMI=Body mass index, VLF=Very low frequency, SRPA=Self-reported physical activity
Comparison of age-matched early and late postmenopausal (17 each) was done, except duration of menopause. Most study parameters were comparable. There was neither a significant nor a specific pattern of difference between the 2 groups [Table 5].
Table 5.
Comparison of heart rate variability parameters in age matched early and late post-menopausal groups (n=17 each)
| Parameter | Early postmenopause (n=17) | Late postmenopause (n=17) | P |
|---|---|---|---|
| Age (years) | 50.76±2.84 | 51.00±3.67 | 0.59 |
| BMI (kg/m²) | 25.69±3.39 | 23.31±4.06 | 0.07 |
| SRPA | 3/13 | 2/14 | - |
| Duration since menopause | 3.55±1.53 | 11.03±4.71 | <0.001* |
| Systolic BP (mmHg) | 116.53±10.91 | 118.00±13.05 | 0.72 |
| Diastolic BP (mmHg) | 72.53±6.59 | 70.76±9.22 | 0.53 |
| Random blood glucose (mg/dl) | 130.53±21.28 | 133.12±21.73 | 0.73 |
| Average R-R interval (ms) | 754.20±105.04 | 796.71±95.96 | 0.23 |
| Heart Rate (bpm) | 79.82±10.76 | 75.76±9.44 | 0.25 |
| Frequency domain indices | |||
| VLF power (ms²/Hz) | 467.35±296.19 | 728.62±674.54 | 0.43 |
| LF power (ms²/Hz) | 277.11±171.04 | 250.72±172.65 | 0.66 |
| HF power (ms²/Hz) | 277.42±247.61 | 198.22±157.91 | 0.45 |
| Normal LF power | 0.55±0.20 | 0.58±0.19 | 0.66 |
| Normal HF power | 0.45±0.20 | 0.42±0.19 | 0.66 |
| Maximum LF (Hz) | 0.06±0.02 | 0.06±0.01 | 0.73 |
| Maximum HF (Hz) | 0.26±0.08 | 0.30±0.08 | 0.19 |
| LF/HF ratio | 1.80±1.93 | 2.06±1.80 | 0.95 |
| Time domain indices | |||
| SDNN (ms) | 26.88±7.82 | 29.54±14.04 | 0.50 |
| RMSSD (ms) | 23.02±11.12 | 24.18±19.13 | 0.76 |
| SDSD (ms) | 21.49±11.98 | 22.48±20.02 | 0.78 |
| NN50 count | 18.88±30.30 | 16.06±33.27 | 0.76 |
| pNN50 (%) | 5.18±8.27 | 4.63±9.82 | 0.84 |
| Geometric measures | |||
| SD1 | 14.50±6.76 | 15.69±13.55 | 0.84 |
| SD2 | 29.46±8.85 | 32.08±14.73 | 0.53 |
| Scatter index (SD1/SD2) | 0.49±0.17 | 0.50±0.36 | 0.39 |
| Mode (ms) | 752.80±102.74 | 788.76±92.58 | 0.29 |
| Triangular HRV index | 6.85±2.26 | 7.08±2.85 | 0.80 |
*Indicates statistical significance. HRV=Heart rate variability, HF=High-frequency, LF=Low-frequency, BP=Blood pressure, BMI=Body mass index, VLF=Very low frequency, SRPA=Self-reported physical activity
Discussion
Women of midlife have cardiovascular risk, which adds to age-induced cardiovascular risk.[15] Cardiac autonomic neuropathy, as evidenced by reduced HRV, is one such cardiovascular risk in women with midlife health.[11] Few studies have reported female disadvantage compared to male in middle age life span,[10,11,16] and few others[3,4,5,6,7,8,9] have underscored the association of menopause with reduced HRV profile. However, the age difference between groups with and without menopause remains the biggest confounder in such menopause HRV association studies.[16] According to STRAW+10 criteria,[12] there are 5 subgroups of reproductive health, namely: Premenopausal, early perimenopausal, late perimenopausal, early postmenopausal and late postmenopausal. But such age matching and sub-grouping is not reported in our population. In the current study, we compared 5 min HRV in these 5 subgroups after age-matching and proper screening for other co-morbidities.
HRV parameters showed no uniform trend of reducing HRV from premenopause to postmenopause, with the intermediate perimenopause group. Such a lack of association is in contrast to most other studies.[3,4,5,6,7,8,9] Probable causes for this negative result can be: (1) Age which was between 40 and 55 years,[11] (2) Exclusion of participants with current diabetes and hypertension that affects HRV in middle to old age population adversely[14] which are included in many studies, (3) Age gap between 3 groups is narrower or matched than studies done elsewhere[3,4,5,6,7,8,9] in which premenopausal group differs by at least a decade than postmenopausal group, (4) Sampling of participants from community from multiple sources rather than single hospital based studies, (5) mean BMI of three groups were 26.18, 26.37, and 24.68, respectively with lesser prevalence of obesity that affects HRV adversely in this age group,[17] (6) Lesser but equal prevalence of physical activity among three subgroups that otherwise confounds HRV,[18] (7) Comparable RPG excluding confounding effect of diabetes,[14] (8) Not much significantly different Heart rate between 3 groups, mean being 80.68, 76.10, and 76.66 respectively as heart rate per se is the main factor affecting HRV,[10] (9) Inclusion of all 3 types of HRV parameters, many of which are missing in other studies. Even if pre-, peri-, and postmenopausal groups exhibited no significant HRV disparities, their mean ages were significantly different, being 42, 44.78, and 50.80, respectively. To further study HRV, they were further divided into the aforementioned 5 subgroups and compared in pairs with nearest neighbourship after meticulous age-matching.
There was no significant difference in HRV parameters between pairs of age-matched premenopausal and early perimenopausal groups; early and late perimenopausal; late perimenopausal and early postmenopausal; early and late postmenopausal. Sample size for each pair was reduced by age matching, but it enabled us to compare HRV after removing age confounding effect at the participant selection level rather than statistical age matching. There was neither a specific trend of incline or decline of HRV between groups nor evident significance in statistics. Such lack of difference can be due to (1) small sample size, (2) HRV itself being an entropy and nonlinear trends are seen in this age group[10] that needs to be reaffirmed by other autonomic function tests[19] that can shoe beyond heart rate changes, (3) Use of short term HRV than long term HRV, latter can further confirm or reject our result,[20] (4) Subjective nature of self-reporting of reproductive health detail, (5) Matching of age in each pair to exact which blunt effect of age between any 2 successive reproductive health groups studied in pair,[4,5,6] (6) exclusion of females with 55–60 years and elderly females that can otherwise bring more progeric effect than current study group with age 40–55 years,[11] (7) Lack of availability of hormonal level that can supersede self-reported menopausal history.[21]
There are few studies supporting this age, more than the reproductive health effect on HRV. The findings of one study suggested that age, but not endogenous estradiol, was primarily responsible for the decrease in measures of HRV and unfavorable response to an acute stressor observed in postmenopausal women than premenopausal women.[22] A study done on the nonlinearity of HRV in healthy aging exhibited that female subjects are more likely to present HRV nonlinear behaviour regardless of the age group,[10] and the same can be a cause of the lack of association of HRV with reproductive health strata. An Indian study showed higher values in time domain and frequency domain HRV parameters for assessing sympathetic functions postmenopausal women when compared to women of the reproductive age group, which was statistically significant; and alike us, they suggested that it can be due to age and hormonal influences.[4] A study done with multiple autonomic function testing revealed that after menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging, and it is even more so with hypertension,[22] which was lacking in our participants. Though HRV can be viewed as a tool to associate with vasomotor symptoms, a study reported that HRV was not associated with frequency or intensity of basal vasomotor symptoms in perimenopausal and postmenopausal women experiencing high levels of these symptoms.[23] They also suggested that autonomic function may be associated with the onset or presence of these symptoms, but not with the number or intensity.[23] We did not have hormonal levels that demarcate menopause, but a recent study noted that the association between serum estradiol levels and cardiovascular events in postmenopausal females remains unclear.[24]
The mean age of menopause is 46 years in India, which is lower than that of Caucasians.[25] This early age of menopause predisposes Indian women to chronic health disorders a decade earlier. Menopausal women are treated by family physicians for psychological health-related[26] and cardiac autonomic health[27] related problems. HRV is a simple yet validated tool that allows a spectrum of measurements that can encompass testing of cardiac autonomic balance, even at the primary care physician and family physician level.[28] Its further utility needs to be confirmed by studies to follow using this HRV gold standard screening test in more defined participants, on a large scale, and using vertical follow-up.
Small sample size, lack of hormonal level, 5 min rather than 24 h HRV, presence of confounder and cross-sectional nature of study were limitations that calls for further study to rectify the same.
Conclusion
Our study among middle-aged healthy women revealed a lack of difference in 5 min HRV parameters between premenopausal, perimenopausal, or postmenopausal women after exact age-matching. Age-matching blunts significant HRV decline from premenopausal to early/late perimenopausal to early/late postmenopausal transition, with age not more than 55 years in our midlife women. It also suggests the study of other confounders than age or menopause for consolidation. This lack of association indicates age and other confounders as a significant attribute for HRV than the reproductive health status of women, and it calls for further study for reinforcement and causality.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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