ABSTRACT: Aim:  The aim of this experiment was to compare the cardiac autonomic activity and BMI in the different phases of menstrual cycle using Heart rate variability. Context Heart rate variability (HRV) in women has been related independently to endogenous sex hormones, hormone replacement therapy, menopause, menstrual cycle, body mass index (BMI), and physical conditioning .It has become a popular non invasive tool for assessing the activities of autonomic nervous system.  Objectives: The aim of this experiment was to compare the cardiac autonomic activity and BMI in the different phases of menstrual cycle using Heart rate variability Design: Prospective comparative study during one menstrual cycle. Study setting A total of 54 female students  were  selected. The selected students were divided into two Group I (BMI < 20) and Group II (BMI >20) the ECG recording   were taken  during  the   3 phases of menstrual  cycle. The analog ECG signal were conveyed through an A/D converter to PC and were analyzed .The frequency domain analysis was done in which the LF,HF  and LF/HF components were studied. Results: In   group II (BMI>20)) there was a significant increase in the LF/HF ratio in the luteal phase of menstrual cycle when compared to other phases of the menstrual cycle. In group I (BMI < 20) there was no statistically significant difference in LF/HF ratio in the three phases . Conclusion: Woman  between  16-25  years  having  less  BMI  had  more  parasympathetic  activity  than those  with  greater  BMI.  In women   with greater BMI cardiac autonomic activity   had a predominant sympathetic profile. 

 INTRODUCTION:

           The heart is an organ under the influence of the autonomic nervous system for the maintenance of homeostasis, and, in this respect, one of its main characteristics is the constant modification of its rate on beat-to beat basis1. Also, it should be emphasized that heart rate is a variable that can be measured in a noninvasive manner with minimal error using simple and low-cost equipment. Today, with the aid of digital computers, it has become possible to study beat-to-beat heart rate variability (HRV) obtained from the R-R intervals in the electrocardiogram (ECG) recordings2, 3, 4. This method has proved to be of great clinical usefulness to evaluate the balance of sympathetic and parasympathetic regulation in several pathological conditions5,6,7,8,9,10. HRV has proved to be a more sensitive tool for the detection of autonomic balance than mean heart rate11            

          Power spectral analysis of heart rate variability (HRV) has been used as a sensitive index of autonomic nervous activities12,13,14,15. In humans, power spectral analysis of R-R interval variability has revealed that there are two major spectral components: the high frequency (HF) component at the respiratory frequency and the low frequency (LF) component at .03 to .15 Hz. The HF component corresponds to the respiratory sinus arrhythmia and is modulated solely by the parasympathetic nervous system14,16,17  ,whereas the LF component corresponds to blood pressure oscillations occurring around .1 Hz, (i.e., the Mayer waves) and is jointly modulated by the sympathetic and parasympathetic nervous systems 18,19. In addition, the LF/HF ratio is also a useful parameter that reflects the balance of autonomic nervous activities 20, 21.

        Heart rate variability (HRV) in women has been related independently to endogenous sex hormones, hormone replacement therapy, menopause, menstrual cycle, body mass index (BMI), and physical conditioning22. Physiological   effects of menstrual cycle on the autonomic function have been extensively examined23. Several studies have found variation of symphatho-vagal activities during the menstrual cycle but the results are inconsistent24, 25. Few studies have evaluated neurocardiac parameters during the various phases of menstrual cycle26; this would be useful and highly relevant for cardiovascular evaluation of women at higher risk to develop heart disease, thus permitting early intervention.

        BMI has traditionally been used to identify individuals who are most likely to be overweight or obese. It is calculated by dividing the weight (kg) by height (meters) squared. Generally high value indicates excessive body fat and consistently relates to increased health risks and mortality27. There is a well recognized relationship between autonomic nervous system function and body habits28. A decrease in parasympathetic nervous system mediated HRV in obesity may in part explain the mortality and morbidity that are associated with the obese state29.  Gonadal  steroids  play  a  major  role  in  the   distribution  of  body  fat. At  the  onset  of  puberty  women  increase  their  body  fat  relative  to  their  muscle  mass. The  distribution  of  body  fat  is  important  clinically  in determination  of  obesity, visceral  central  adiposity  is  associated  with  a  greater  risk  of  metabolic  &  cardiovascular  disorders including  insulin  resistance, type2  diabetes,  hypertension &  coronary  heart  disease30.Obesity can be determined by BMI30. 

         It is questionable that whether in general population low HRV is a consequence of a disease or an indicator of an underlying mechanism for future disease. Several studies suggest that, there are definite changes in the HRV in the different phases of the menstrual cycle31 but studies are lagging correlating the cardiac autonomic activity, menstrual cycle and BMI in young females in different phases of menstrual cycle.  The present study aims to describe the HRV and assesses its association with BMI, and menstrual cycle in healthy young women in time domain and frequency domain method in different phases of menstrual cycle

Materials and Methods: A total of 54 female  students  studying  their  MBBS  Course  in  Kasturba Medical College  Bejai,   Mangalore were  selected .  The selected  students  were  in  the  age  group  18-25 years who were  having regular ,28-day   menstrual cycles  for at least   6 months prior   to this   study.   After detailed enquiry of the medical history of the subjects, those with history of smoking, alcoholism, medical illness were excluded. Subjects on oral contraceptive pill, hormonal replacement therapy, drugs that alter the cardiovascular functions were also excluded from the study. Informed written consent was obtained from all participants, and the experiment protocol was approved by Ethics committee of the college.

Experimental protocol: The selected students were divided into two group based on their BMI values, Group I (n=25; n denotes the number of individuals in each group) consisted of BMI<20 and Group II (n=29) consisted of individuals having BMI>20.

The ECG recording were  taken  during  the  following  3 phases

Menstrual  phase (M) – 1st   to  5th  day  of  bleeding ,

Follicular    phase (F) – 6th   day   to 14th   day of   menstrual   cycle.

Luteal  phase (L) – 15th  day  to  28th  day  or the  next  menstrual  bleeding.

 Heart rate Variability was recorded using Digital data Acquisition system, HRV soft 1.1

VERSION, AIIMS, NEW DELHI. A high quality ECG recording was taken under standardized condition to minimize artifacts. The ECG signal was first analogally recorded & then digitally converted and analyzed in the frequency domain.

          The experiments were carried out in the morning in fasting state. Subjects refrained from caffeinated beverages for at least 12 hours prior to the experiments and had completed their evening meal by 9 P.M. they were also instructed to avoid strenuous physical activity from the previous evening. The recordings of ECG of all subjects were done by the same person of our team in order to avoid any inter–observer error. To quantify heart rate, the analog  ECG signal was obtained using lead II to obtain a QRS complex of sufficient amplitude and stable base line. ECG signals were conveyed through an A/D converter to PC and were analyzed offline after visual checking of abnormal ECG. Heart rate variation during normal breathing for a period of 5 minutes was recorded, with subject supine, awake and resting. In the present study ,in the frequency domain analysis the two main frequency components that is the low frequency (LF) components (0.04 to 0.15Hz) and the high frequency (HF) components (0.15 to 0.4 Hz) was measured.  We have also evaluated and analyzed the ratio LF/HF32,33,34,35.

Statistical analysis: The  statistical   analysis  was  done  using  ANOVA (Analysis  of  variance), student’s  unpaired  T  test, Mannwhitney U test, Tukey’s  Test.   P  value  was  taken  as  significant  at  5 percent  confidence  level.(p < 0.05)

 

 Table 1:Effect of variation in HRV in the three different phases of menstrual cycle  in group I (BMI <20 )individuals (n=25)

 

                                                BMI < 20
  

 

 LF  HF  LF/HF
 Menstrual

 

 38.5 ± 6.6

 

 

 

 

 

 61.4 ± 6.63

 

 

 

 

 

 0.64±0.18

 

 

 

 

 

  

Follicular

 

 39.18± 16.86

 

 

 

 

 

60.81 ± 16.86 0.76±0.54 
 Luteal

 

 

 

 

 

65.95 ± 1.77 

 

 

 

 

69.70± 2.94  0.94 ±0.04 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2:Effect of variation in HRV in the three different phases of menstrual cycle  in group II (BMI >20 )individuals (n=29)

 

                                                BMI>20
  

 

 LF  HF  LF/HF
 Menstrual

 

42.64 ± 23.05  

 

 

61.05 ± 17.59  

 

 

0.83±0.79‡ ‡ ‡  

 

  

Follicular

 

50.4 ± 17.37  

 

 

49.59 ± 17.37  1.23±0.66*** 
 Luteal

 

 

 

 

 

62.74 ± 14.27  

 

 

37.25± 14.27  2.03 ±1.03 

P< 0.0001‡ ‡ ‡   – Menstrual phase compared to Luteal phase

P< 0.0001*** – Follicular phase compared to Luteal phase

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3: – Effect of variation in BMI on HRV during Luteal phase of menstrual cycle (n=54) in Frequency domain analysis

 

 BMI<20 LF HF LF/HF Ratio
65.95 ± 1.77 

 

 

 

 

69.70± 2.94  0.94 ±0.04 
BMI >20 62.74± 14.27 

 

 

41.11 ± 15.80 2.03 ±1.03 ***

 

 

 

 

 

 

 

 

 

P< 0.0001*** – Comparison between BMI<20 and BMI >20

 

 

RESULTS:

 In the present study, the variations of   LF, HF, and LF/HF ratio in group I (table1) showed no statistically significant difference in between the three phases of menstrual cycle. Further in group II (table II) there was a significant increase in the LF/HF ratio in the luteal phase of menstrual cycle when compared to other phases of the menstrual cycle (P<0.001 for both). Analysis of HRV during the luteal phase of the menstrual cycle in between group I and group II (table 3), showed a statistically significant increase in the LF/HF ratio (P<0.001) in group II.

DISCUSSION:

            Autonomic regulation of the heart in the normal woman differs during the menstrual cycle. Cardiac autonomic functions can be influenced by multiple factors36.  The results of the present study support that BMI plays an important role in the womens cardiac autonomic modulation. Our results clearly demonstrated a significant difference in the autonomic nervous activity in the luteal phase of the menstrual cycle in young females with increased BMI. 

              Power spectral analysis of HRV has more sensitivity in assessing the slight fluctuation of autonomic activities during menstrual cycle37 .Our previous study provides findings that autonomic nervous activities fluctuate during Menstural cycle. Luteal phase of MC was associated with a significant increase in the LF component and a significant decrease in the HF component, resulting in a high LF/HF ratio. Our findings were in agreement with earlier work who observed that sympathetic nervous activities are predominant in the luteal phase as compared with follicular phase38, 39.

                  In this study BMI was a major determinant of cardiac autonomic nervous modulation. Woman between 16-25 years having less BMI had more parasympathetic activity than those with greater BMI.  In women with greater BMI cardiac autonomic activity had a predominant sympathetic profile. LF/HF ratio is the most sensitive indicator of sympathovagal balance40 In the present study increase in BMI showed a higher increase in the LF/HF ratio in the luteal phase of the menstrual cycle, this indicated presence of sympathovagal imbalance (SVI).

            In summary, this study has shown that women with increased BMI had significant changes in autonomic nerve function that included reduced parasympathetic control and elevated sympathovagal modulation. Even though these women did not come under the obese group, they are more prone to become obese. Clearly more work is needed to explore this relationship at the later age. It is well established that a lower heart rate variability is associated with increased cardiovascular morbidity. Detection of sympatho vagal inbalance at an early age based on BMI and necessary life style modification   could decrease the incidence of cardiovascular diseases.

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