Keywords
polycystic ovary syndrome - cardiac autonomic modulation - hyperandrogenism - spectral
analysis - symbolic analysis
Descritores
síndrome dos ovários policísticos - modulação autonômica cardíaca - hiperandrogenismo
- análise espectral - análise simbólica
Introduction
Polycystic ovary syndrome (PCOS) is a disease of endocrine origin that affects ∼ 5
to 16% of women of childbearing age.[1] In 2003, the Rotterdam consensus proposed that PCOS could be diagnosed after excluding
other causes of menstrual irregularity, the presence of ovary cysts, and hyperandrogenism,[2] and their healthcare providers must be aware of the possible risks and complications
of PCOS including those related to the cardiovascular system, and endocrine, metabolic,
and body composition parameters.[2]
[3]
[4]
[5]
[6]
The cause and effect relationship between increased insulin resistance (IR) and excess
testosterone is evident in PCOS. This has been associated with increased visceral
fat and metabolic syndrome,[4]
[5]
[6]
[7] which predisposes to the development of metabolic chronic diseases[2]
[6]
[7] and of cardiovascular disorders that directly impair the physiology of normal heart
function and are often accompanied by impairments in cardiac autonomic control.[8]
[9]
[10] It has been demonstrated that there is a cardiovascular autonomic imbalance in women
with PCOS, with increased autonomic sympathetic cardiac modulation and reduced parasympathetic
modulation, which increases the risk of cardiovascular disease.[3]
[10]
[11]
Noninvasive, reproducible, and low-cost tests have been used to evaluate autonomic
function, specifically, heart rate variability (HRV),[12]
[13]
[14]
[15] which can be analyzed in both a linear and in a nonlinear manner. On the other hand,
the tilt test, which involves autonomic provocations by means of postural changes
from supine to orthostatic positions (standing, 90°; passively or actively), allows
a better evaluation of the autonomic modulation.[16]
[17]
To our knowledge, there are no data available on HRV after a second of two consecutive
tilt tests, nor on whether symbolic analyses would express results similar to those
of spectral analyses. An adaptation of HRV to the second consecutive test in the PCOS
group could represent an auxiliary form of training that controls the modulation of
the cardiac autonomic cardiovascular system. Thus, the present study aimed to analyze
the behavior of cardiac autonomic modulation via spectral and symbolic analyses of
HRV in women with PCOS subjected to two consecutive tilt tests.
Methods
Participants and Methods
In the present case-control study, women with PCOS and controls with regular menstrual
cycles were included. The study sample comprised 64 women, 32 with PCOS and 32 controls
(without PCOS), aged between 18 and 37 years old, with body mass indexes (BMIs) between18
and 39.9 kg/m2 who did not engage in regular supervised physical activity. Women with PCOS were
selected from outpatient clinics of the Human Reproduction Sector of the Department
of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo,
Ribeirão Preto, state of São Paulo, Brazil, and the healthy control group (CG) participants
were recruited from the women who had routine gynecological examinations at Basic
Health Clinics. Polycystic ovary syndrome was diagnosed using the criteria established
by the Rotterdam consensus and was based on the presence of at least two of the following
conditions: oligomenorrhea or amenorrhea; clinical and/or biochemical signs of hyperandrogenism;
polycystic ovaries detected by pelvic ultrasound.[2] The inclusion criteria for CG were: without PCOS, menstrual cycles occurring at
intervals of between 22 and 35 days; duration of menses from 3 to 7 days.[18] The exclusion criteria for both groups were: other systemic diseases, smoking, pregnancy,
use of medications that might interfere with the hypothalamus–pituitary–ovarian axis,
and drugs that definitively interfered with the hypothalamic-pituitary-axis or cardiac
autonomic modulation.
The present study was conducted in accordance with the ethical standards set forth
in the Helsinki Declaration of 1975 and was approved by the Human Research Ethics
Committee of the Clinical Hospital of the School of Medicine of Ribeirão Preto, University
of São Paulo, Ribeirão Preto, state of São Paulo, Brazil (case HCRP N. 13475/2009).
Pelvic Ultrasonography
All of the women underwent transvaginal pelvic ultrasonography examinations using
a Voluson 730 Expert machine (GE Medical Systems, Zipf, Austria) to evaluate for polycystic
ovaries.[19]
Biochemical Measurements
The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
prolactin, estradiol, homocysteine, sex hormone-binding globulin (SHBG), thyroid stimulating
hormone (TSH), and fasting insulin were determined using a chemiluminescence assay
(IMMULITE 2000 Immunoassay System; Siemens, Munich, Germany). Testosterone, androstenedione,
and 17-hydroxyprogesterone (17- OHP) levels were measured using radioimmunoassay (IMMULITE
1000; Siemens, Munich, Germany), and glucose levels were assessed using the glucose
oxidase method. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL),
and triglycerides (TG) were assessed using an enzymatic method, and low-density lipoprotein
cholesterol (LDL) was calculated using the Friedewald formula: [LDL = TC - (HDL + TG/5)].[20] The free androgen index (FAI) was determined using total testosterone [(nmol/L−1)/ SHBG (nmol/L−1) × 100],[21] and IR (insulin resistance) was quantified using the homeostatic model assessment
of IR (HOMA-IR) ([fasting glycemia level (mg/dL−1) _ 0.05551] x [fasting insulin level (μIU/Ml−1)]/22.5).[22]
Anthropometry and Body Fat
Anthropometric measurements were obtained according to the recommendations of the
International Society for the Advancement of Kinanthropometry.[23]
[24]
[25]
[26]
[27]
[28] Height was recorded to the nearest 0.1 cm using a standard anthropometer, and weight
to the nearest 0.5 kg using a weight scale (Filizola, São Paulo, SP, Brazil). A nonelastic
flexible measuring tape was used to measure waist, hip, and abdominal circumferences,
with all measurements taken by a single evaluator and recorded to the nearest 0.1 cm.
Waist circumference (WC) was measured at the mid-point between the lower ribs and
the iliac crest. Hip circumference was measured around the greatest circumference
of the gluteal region, while abdominal circumference was measured just under the umbilicus
(umbilical waist circumference). The following anthropometric indices were calculated:
BMI (kg/m2), calculated by dividing body weight by the square of the height, and the waist-to-hip
ratio (WHR), calculated by dividing WC (cm) by hip circumference (cm). The body fat
percentage (%) was assessed using a QDR Discovery Series dual energy- X-ray absorptiometry
(DXA) device (Hologic, Marlborough; MA, USA) and the 5 Discovery Wi model software
(S/N 84826) version 13.0 provided by the manufacturer (Waltham, MA).
Heart Rate Variability Analysis
Spectral and symbolic analyses of HRV were conducted to evaluate cardiac autonomic
modulation, using a custom-made computer software (CardioSeries version 2.4; http://sites.google.com/site/cardioseries). The volunteers were asked not to consume alcohol and caffeine or participate in
exercise and to maintain a regular diet over the 48 hours before the examination.
Recordings for the spectral and symbolic analysis of HRV were performed using ECG
signals (AD Instruments, Sydney, Australia) between 8:00 and 11:00 hours over a 60-minute
period according to the following protocol: 20 minutes in the supine position on a
special motorized tilt table (orthostatic table), and 10 minutes of recording with
initial adaptation of the phase followed by 10 minutes of recording in the supine
position. Subsequently, the table motor was switched on and the volunteers were moved
passively from the supine position to the orthostatic position (90°) for 10 minutes,
returning to the supine position for another 10 minutes. Finally, the volunteers were
moved passively a second time, from the supine position to the orthostatic position
(90°) for 10 minutes, and returning once more to the supine position, where they remained
for another 10 minutes.
For the spectral analysis, the R-R interval (RRi) values obtained were resampled (3 Hz)
using cubic spline interpolation to adjust the time interval between heartbeats. These
were divided into segments of 512 values each with 50% overlap (Welch protocol). Each
RRi stationary segment was subjected to fast Fourier transform, after applying a Hanning
window function. The oscillatory components were classified as either low frequency
(LF: 0.04–0.15 Hz) or high frequency (HF: 0.15–0.5 Hz). The mean values of the power
spectral densities of RRi in both bands (LF and HF) are expressed in absolute units
(ms2). The relative power (%), also known as normalized units (n.u.) in each frequency
band, as well as the LF/HF ratio powers, were calculated by subtracting the very low
frequency (VLF < 0.04 Hz) values. The normalization tended to minimize the effect
of changes in total power on the LF and HF component values.[12]
[24] For this reason, in addition, an individualized analysis of the LF/HF ratio was
used to verify the predominance of sympathetic and parasympathetic autonomic modulation
in women with metabolic syndrome of both groups, in all the five moments, in order
to minimize the effects of confouders.
For the symbolic analysis, the methodology used was described previously,[13] where the lowest iRR of the highest RRi was subtracted and the resulting delta was
divided by six, generating six levels with identical intervals (0 to 5). Subsequently,
the distribution of the iRR series was performed according to its duration of time.
Each symbolic sequence consisted of the sequential values of three iRRs (a symbolic
crack) that were transformed into symbols (0, 1, 2, 3, 4, and 5), according to the
level that fit each value of iRR. For the final analysis, the following cracking patterns
were used: 1) 0V: unchanged patterns, with three equal symbols, for example (2,2,2)
or (5,5,5); 2) 1V: patterns with one variation, that is, patterns with two equal consecutive
symbols and the remaining ones were different symbols, for example (3,2,2) and (3,3,2);
3) 2LV: patterns with two variations, with the three symbols forming an ascending
or descending ramp, for example, (5,4,2) or (1,2,4); and 4) 2ULV: patterns with two
variations in reverse, where the three symbols formed a peak or a trough, such as
(3,5,3) or (4,1,2). At the end, the 2LV and 2ULV values were summed and presented
as 2V. Previous studies have shown that 0% represents sympathetic cardiac autonomic
modulation, 2V% represents parasympathetic modulation, and 1V represents simultaneity
of the two modulations.[13]
[15]
Statistical Analysis
The Shapiro-Wilk test was used to analyze the distribution of quantitative data, with
95% significance in each of the analyzed variables. For comparison of the anthropometric,
biochemical, and HRV variables between groups (intergroup), the t-test was used to analyze the parametric data, and the Mann-Whitney U test was used
for nonparametric data. For comparisons between the bench press, tilt 1, bench press
2, tilt 2, and bench press 3 (intragroup), a one-way analysis of variance (ANOVA)
was used. Data are presented as means ± standard errors of the means (SEMs). The differences
were considered significant when p < 0.05. SigmaStat 11.0 software (Systat Software Inc., San Jose, CA, USA) was used
for the statistical analysis.
Results
The comparison between PCOS and CG groups with respect to anthropometric data, body
fat percentiles, and biochemical parameters are shown in [Table 1]. The PCOS group had higher values of fasting insulin (p = 0.014), testosterone (p = 0.036), and HOMA-IR (p = 0.012) and FAI (p = 0.010) scores comparable to the CG. No differences were observed in the other parameters.
Table 1
Comparison of anthropometry, body fat and biochemical parameters among women in the
control group (CG) without Polycystic Ovary Syndrome and women with Polycystic Ovary
Syndrome (PCOS)
|
Comparison
|
CG (n = 32)
|
PCOS (n = 32)
|
|
Anthropometry parameters
|
|
Age, years
|
29.4 (0.90)
|
27.0 (0.93)
|
|
Weight, Kg
|
69 (2.57)
|
75 (3.04)
|
|
Height, m
|
1.61 (0.01)
|
1.62 (0.01)
|
|
BMI
|
26.8 (1.02)
|
28.8 (1.15)
|
|
WC, cm
|
78 (2.00)
|
89 (2.45)
|
|
HC, cm
|
105 (1.91)
|
108 (1.94)
|
|
WHR
|
0.74 (0.01)
|
0.76 (0.01)
|
|
Body Fat, %
|
38.8 (1.23)
|
40.5 (0.92)
|
|
Biochemical parameters
|
|
Total Cholesterol, mg/dL
|
195 (8.99)
|
198 (6.36)
|
|
Triglycerides, mg/dL
|
95 (6.86)
|
128 (12.87)
|
|
LDL, mg/dL
|
123 (7.36)
|
119 (5.29)
|
|
HDL, mg/dL
|
52 (2.10)
|
54 (2.04)
|
|
Fasting Insulin, mg/dL
|
5.88 (0.95)
|
9.34 (1.16)[*]
|
|
Fasting Glycemia, mg/dL
|
97 (3.22)
|
100 (3.45)
|
|
Homa-IR
|
1.42 (0.26)
|
2.36 (0.33)[*]
|
|
Homocysteine, µmol/L
|
7.37 (0.25)
|
7.86 (0.40)
|
|
TSH, uIU/mL
|
2.01 (0.98)
|
2.48 (1.27)
|
|
PRL, ng/ml
|
13.9 (6.58)
|
16.1 (16.1)
|
|
17-OHP, ng/dL
|
105 (63)
|
113 (62)
|
|
FSH, uIU/mL
|
4.26 (0.43)
|
4.72 (0.50)
|
|
LH, uUI/mL
|
5.58 (1.19)
|
6.96 (1.21)
|
|
Testosterone, ng/dL
|
66 (4.67)
|
86 (6.68)[*]
|
|
Androstenedione, ng/dL
|
102 (5.98)
|
112 (8.72)
|
|
SHBG, nmol/L
|
65 (6.52)
|
56 (7.64)
|
|
FAI
|
4.65 (0.54)
|
7.90 (0.91)[*]
|
Abbreviations: %, percentage; µmol/L / L - micromole / liter; 17-OHP - 17-hydroxyprogesterone; BMI, body mass index; CG, control group; cm, centimeters;
FAI, free androgen index; FSH, follicle stimulating hormone; HC, hip circumference;
HDL, High Density Lipoproteins; HOMA-IR, homeostatic model assessment; LDL, Low Density
Lipoproteins; LH, luteinizing hormone; mg/dL, milligrams / decilitre; ng / dL, nanogram
/ deciliter; ng / ml, nanograms per milliliters; nmol / L, nanomol / Liter; PCOS,
polycystic ovary syndrome; PRL, prolactin; SHBG, sex hormone binding globulin; TSH,
thyroid stimulating hormone; uIU / mL, international microunits / milliter; WC, waist
circumference; WHR, hip waist ratio.
The data are presented in mean and standard deviation.
*
p < 0.05.
[Table 2] shows the comparison between the PCOS and CG groups with respect to the HRV data
evaluated at the supine 1, supine 2, and supine 3 moments. No differences were identified
at supine moment 1. At supine 2, the PCOS group had higher values for LF (n.u.) (p = 0.030) and the LF/HF ratio (p = 0.030), and a lower value for HF (n.u.) (p = 0.30). This superiority in the PCOS group persisted at supine 3 for all three variables:
LF (n.u.) (p = 0.020) and LF/HF ratio, (p = 0.020) and a lower value for HF (n.u.) (p = 0.20). In addition, there was superiority of the PCOS group in the LF value (ms)
(p = 0.002).
Table 2
Comparison of cardiac autonomic modulation through spectral and symbolic analysis
in the supine 1, supine 2 and supine 3 periods among control women (CG) without Polycystic
Ovary Syndrome and women with Polycystic Ovary Syndrome (PCOS)
|
Supine 1
|
Supine 2
|
Supine 3
|
|
CG
|
PCOS
|
CG
|
PCOS
|
CG
|
PCOS
|
|
Spectral Analysis
|
|
|
|
|
|
RMSSD, ms
|
55 (6.3)
|
54 (5.2)
|
72 (7.1)
|
69 (6.7)
|
70 (6.2)
|
75(7.5)
|
|
iRR, ms
|
896 (20)
|
901 (15)
|
967 (21)
|
972 (16)
|
978 (23)
|
978(17)
|
|
LF, ms2
|
728 (145)
|
883 (113)
|
910 (152)
|
1220 (162)
|
1053 (189)
|
1582 (193)B
|
|
HF, ms2
|
1520 (433)
|
1378 (250)
|
2385 (570)
|
2073 (404)
|
2046 (384)
|
2367 (478)
|
|
LF, n.u.
|
38 (2.5)
|
44 (2.7)
|
35 (2.8)
|
43 (3.0)A
|
37 (2.4)
|
47 (3.2)B
|
|
HF, n.u.
|
62 (2,5)
|
56 (2.7)
|
65 (2.8)
|
57 (3.0)A
|
63 (2.4)
|
53 (3.2)B
|
|
LF/HF ratio
|
0.70 (0.08)
|
0.95 (0.12)
|
0.69 (0.13)
|
1.02 (0.19)A
|
0.69 (0.09)
|
1.34 (0.31)B
|
|
Variance, ms2
|
2942 (633)
|
3279 (405)
|
4181 (750)
|
4428 (626)
|
4139 (629)
|
5643 (753)
|
|
Symbolic Analysis
|
|
|
|
|
|
|
0 V, %
|
9.7 (1.3)
|
11 (1.39)
|
7.8 (1.0)
|
10 (2.41)
|
8.7 (1.2)
|
12 (1.69)
|
|
1 V, %
|
40 (1.2)
|
44 (0.9)
|
37 (1.1)
|
39 (1.1)
|
38 (1.1)
|
39 (1.0)
|
|
2 LV, %
|
20 (1.1)
|
17 (1.0)
|
20 (1.4)
|
17 (1.1)
|
18 (1.2)
|
17 (1.0)
|
|
2 UV, %
|
36 (2.3)
|
27 (1.6)
|
36 (2.2)
|
33 (1.9)
|
30 (2.3)
|
32 (2.0)
|
|
2 V Total, %
|
50 (2.2)
|
45 (2.0)
|
54 (2.0)
|
51 (2.2)
|
54 (2.0)
|
49 (2.4)
|
|
0V/2V ratio
|
0.26 (0.06)
|
0.35 (0.08)
|
0.18 (0.05)
|
0.28 (0.07)
|
0.21 (0.05)
|
0.34 (0.06)
|
Abbreviations: %, percentage; CG, control group; HF, High Frequency; LF, Low Frequency;
ms, milliseconds; n.u., normalized units; PCOS, polycystic ovary syndrome.
The data are presented in mean and standard error.
Supine 2 - CG vs PCOS (A p < 0.05); Supine 3 - CG vs PCOS (B p < 0.05).
[Table 3] shows the comparisons between the PCOS and CG groups with respect to the HRV data
evaluated at tilt 1 and tilt 2 moments. At tilt 1, the PCOS group had higher values
of LF (ms) (p = 0.025), LF (n.u.) (p = 0.009), and LF/HF ratio (p = 0.009), and variance (ms) (p = 0.026) and lower HF (n.u.) (p = 0.009). No differences were observed between groups at tilt 2.
Table 3
Comparison of cardiac autonomic modulation through spectral and symbolic analysis
in the supine 1, supine 2 and supine 3 periods among control women (CG) without Polycystic
Ovary Syndrome and women with Polycystic Ovary Syndrome (PCOS)
|
Tilt 1
|
Tilt 2
|
|
CG
|
PCOS
|
CG
|
PCOS
|
|
Spectral Analysis
|
|
RMSSD, ms
|
24 (3.0)
|
21 (1.6)
|
25 (3.6)
|
21 (1.7)
|
|
iRR, ms
|
720 (17)
|
711 (12)
|
712 (17)
|
708 (13)
|
|
LF, ms2
|
595 (115)
|
759 (82)A
|
860 (130)
|
863 (140)
|
|
HF, ms2
|
367 (107)
|
251 (42)
|
422 (150)
|
237 (43)
|
|
LF, n.u.
|
66 (2.7)
|
76 (2.2)A
|
73 (2.5)
|
78 (2.3)
|
|
HF, n.u.
|
34 (2.7)
|
24 (2.2)A
|
27 (2.5)
|
22 (2.3)
|
|
LF/HF ratio
|
2.54 (0.30)
|
4.88 (0.73)A
|
3.98 (0.49)
|
5.44 (0.69)
|
|
Variance, ms2
|
1579 (246)
|
1896 (172)A
|
2217 (367)
|
2206 (231)
|
|
Symbolic Analysis
|
|
0 V, %
|
29 (2.4)
|
34 (2.10)
|
33 (2.3)
|
38 (2.05)
|
|
1 V, %
|
45 (0.9)
|
46 (0.8)
|
45 (0.8)
|
44 (0.6)
|
|
2 LV, %
|
13 (1.0)
|
10 (0.9)
|
11 (0.9)
|
9.2 (0.9)
|
|
2 UV, %
|
9.9 (1.3)
|
9.6 (0.9)
|
12 (1.4)
|
8.6 (0.9)
|
|
2 V Total, %
|
25 (2.2)
|
20 (1.6)
|
21 (2.0)
|
18 (1.6)
|
|
0V/2V ratio
|
2.39 (0.68)
|
2.74 (0.52)
|
2.70 (0.50)
|
3.13 (0.46)
|
Abbreviations: %, percentage; CG, control group; HF, High Frequency; LF, Low Frequency;
ms, milliseconds; n.u. normalized units; PCOS, polycystic ovary syndrome.
Tilt 1 - CG vs PCOS (A p < 0.05).
The data are presented in mean and standard error.
[Table 4] shows the HRV comparisons (intergroup) between supine 1, tilt 1, supine 2, tilt
2, and supine 3 moments in the CG group. The tilt 1 and tilt 2 moment presented higher
values of LF (n.u.), LF/HF, 0V (%), and 0V/2V, and lower values in the square root
of the square mean of the differences between adjacent normal RR intervals (RMSSD)
and iRR HF (ms), HF (n.u.), variance, 2 LV, 2UV, 2 total V when compared with supine
1, supine 2, and supine 3 moments. When comparing the supine moments 1, 2, and 3 with
each other, bench press 3 presented higher values those of than supine 1 in RMSSD,
iRR, HF (ms) and variance, and lower values than those of 1V and 2 UV, in addition
to a lower value for 2UV in comparison to supine moment 2. Supine moment 2 was superior
compared with supine 1 in RMSSD, iRR, HF (ms), variance, and values < 1V. Regarding
the comparison between tilt 1 and tilt 2, tilt 2 showed higher values for LF (n.u.),
the LF/HF ratio, 0V, 2UV, and the 0V/2V ratio, and lower values for HF (n.u.).
Table 4
Cardiac autonomic modulation through spectral and symbolic analysis in the supine
1, tilt 1, supine 2, tilt 2 and supine 3 periods among control women (CG) without
Polycystic Ovary Syndrome
|
CG (n = 32)
|
|
Supine 1
|
Tilt 1
|
Supine 2
|
Tilt 2
|
Supine 3
|
|
Spectral Analysis
|
|
RMSSD, ms
|
55 (6.3)
|
24 (3.0)J
|
72 (7.1)HI
|
25 (3.6)EG
|
70 (6.2)ACD
|
|
iRR, ms
|
896 (20)
|
720 (17)J
|
967 (21)HI
|
712 (17)EG
|
978 (23)ACD
|
|
LF, ms2
|
728 (145)
|
595 (115)
|
910 (152)
|
860 (130)
|
1053 (189)
|
|
HF, ms2
|
1520 (433)
|
367 (107)J
|
2385 (570)HI
|
422 (150)EG
|
2046 (384)ACD
|
|
LF, n.u.
|
38 (2.5)
|
66 (2.7)J
|
35 (2.8)H
|
73 (2.5)EFG
|
37 (2.4)AC
|
|
HF, n.u.
|
62 (2.5)
|
34 (2.7)J
|
65 (2.8)H
|
27 (2.5)EFG
|
63 (2.4)AC
|
|
LF/HF ratio
|
0.70 (0.08)
|
2.54 (0.30)J
|
0.69 (0.13)H
|
3.98 (0.49)EFG
|
0.69 (0.09)AC
|
|
Variance, ms2
|
2942 (633)
|
1579 (246)J
|
4181 (750)HI
|
2217 (367)EF
|
4139 (629)ACD
|
|
Symbolic Analysis
|
|
0 V, %
|
9.7 (1.3)
|
29 (2.4)J
|
7.8 (1.0)H
|
33 (2.3)EFG
|
8.7 (1.2)AC
|
|
1 V, %
|
40 (1.2)
|
45 (0.9)J
|
37 (1.1)HI
|
45 (0.8)EG
|
38 (1.1)ACD
|
|
2 LV, %
|
20 (1.1)
|
13 (1.0)J
|
20 (1.4)H
|
11 (0.9)EG
|
18 (1.2)AC
|
|
2 UV, %
|
36 (2.3)
|
9.9 (1.3)J
|
36 (2.2)H
|
12 (1.4)EFG
|
30 (2.3)ABCD
|
|
2 V Total, %
|
50 (2.2)
|
25 (2.2)J
|
54 (2.0)H
|
21 (2.0)EFG
|
54 (2.0)AC
|
|
0V/2V ratio
|
0.26 (0.06)
|
2.39 (0.68)J
|
0.18 (0.05)H
|
2.70 (0.50)EFG
|
0.21 (0.05)AC
|
Abbreviations: %, percentage; CG, control group; HF, High Frequency; LF, Low Frequency;
ms, milliseconds; n.u., normalized units.
The data are presented in mean and standard error.
Supine 3 vs Tilt 2 (A p < 0.05); Supine 3 vs Supine 2 (B p < 0.05); Supine 3 vs Tilt 1 (C p < 0.05); Supine 3 vs Supine 1 (D p < 0.05); Tilt 2 vs Supine 2 (E p < 0.05); Tilt 2 vs Tilt 1 (F p < 0.05); Tilt 2 vs Supine 1 (G p < 0.05); Supine 2 vs Tilt 1 (H p < 0.05); Supine 2 vs Supine 1 (I p < 0.05); Tilt 1 x Supine 1 (J p < 0.05).
[Table 5] shows the HRV comparisons between supine 1, tilt 1, supine 2, tilt 2 and supine
3 moments in the PCOS group. The tilt 1 and tilt 2 moments presented higher values
for LF (n.u.), LF/HF, 0V, and 0V/2V, and lower values for RMSSD, iRR, HF (ms), HF
(n.u.), variance, 2 LV, 2UV, 2 total V when compared with the supine 1, supine 2,
and supine 3 moments. Only LF (ms) and 1V tilt 2 presented inferior and superior values,
respectively, in relation to supine moment 2. When comparing supine moments 1, 2,
and 3 with each other, supine 3 values were higher than those of supine 1 for RMSSD,
iRR, LF (ms), variance (ms), 0V, 2UV, and 2V total and lower values than 1V, in addition
to higher values for LF (ms) and variance (ms) in relation to supine moment 2. Supine
moment 2 presented superiority in relation to supine 1 in the RMSSD, iRR, LF (ms),
HF (ms), variance (ms), 2UV and 2V total and values lower than those of 0V and 1V.
Regarding the comparison between tilt 1 and tilt 2, tilt 2 showed higher values for
variance, 0V, and the 0V/2V ratio, and lower values than those of 2LV, 2UV, and 2UV
total.
Table 5
Cardiac autonomic modulation through the spectral and symbolic analysis in the supine
1, tilt 1, supine 2, tilt 2 and supine periods among women with Polycystic Ovary Syndrome
(PCOS)
|
PCOS (n = 32)
|
|
Supine 1
|
Tilt 1
|
Supine 2
|
Tilt 2
|
Supine 3
|
|
Spectral Analysis
|
|
RMSSD, ms
|
54 (5.2)
|
21 (1.6)J
|
69 (6.7)HI
|
21 (1.7)EG
|
75 (7.5)ACD
|
|
iRR, ms
|
901 (15)
|
711 (12)J
|
972 (16)HI
|
708 (13)EG
|
978 (17)ACD
|
|
LF, ms2
|
883 (113)
|
759 (82)
|
1220 (162)HI
|
863 (140)E
|
1582 (193)ABCD
|
|
HF, ms2
|
1378 (250)
|
251 (42)J
|
2073 (404)HI
|
237 (43)EG
|
2367 (478)ACD
|
|
LF, n.u.
|
44 (2.7)
|
76 (2.2)J
|
43 (3.0)H
|
78 (2.3)EG
|
47 (3.2)AC
|
|
HF, n.u.
|
56 (2.7)
|
24 (2.2)J
|
57 (3.0)H
|
22 (2.3)EG
|
53 (3.2)AC
|
|
LF/HF ratio
|
0.95 (0.12)
|
4.88 (0.73)J
|
1.02 (0.19)H
|
5.44 (0.69)EG
|
1.34 (0.31)AC
|
|
Variance, ms2
|
3279 (405)
|
1896 (172)J
|
4428 (626)HI
|
2206 (231)EFG
|
5643 (753)ABCD
|
|
Symbolic Analysis
|
|
0 V, %
|
11 (1.39)
|
34 (2.10)J
|
10 (2.41)HI
|
38 (2.05)EFG
|
12 (1.69)ACD
|
|
1 V, %
|
44 (0.9)
|
46 (0.8)
|
39 (1.1)HI
|
44 (0.6)E
|
39 (1.0)ACD
|
|
2 LV, %
|
17 (1.0)
|
10 (0.9)J
|
17 (1.1)H
|
9.2 (0.9)EFG
|
17 (1.0)AC
|
|
2 UV, %
|
27 (1.6)
|
9.6 (0.9)J
|
33 (1.9)HI
|
8.6 (0.9)EFG
|
32 (2.0)ACD
|
|
2 V Total, %
|
45 (2.0)
|
20 (1.6)J
|
51 (2.2)HI
|
18 (1.6)EFG
|
49 (2.4)ACD
|
|
0V/2V ratio
|
0.35 (0.08)
|
2.74 (0.52)J
|
0.28 (0.07)H
|
3.13 (0.46)EFG
|
0.34(0.06)AC
|
Abbreviations: %, percentage; HF, High Frequency; LF, Low Frequency; ms, milliseconds;
n.u., normalized units; PCOS, polycystic ovary syndrome.
The data are presented in mean and standard error.
Supine 3 vs Tilt 2 (A p < 0,05); Supine 3 vs Supine 2 (B p < 0.05); Supine 3 vs Tilt 1 (C p < 0.05); Supine 3 vs Supine 1 (D p < 0.05); Tilt 2 vs Supine 2 (E p < 0.05); Tilt 2 vs Tilt 1 (F p < 0.05); Tilt 2 vs Supine 1 (G p < 0.05); Supine 2 vs Tilt 1 (H p < 0.05); Supine 2 vs Supine 1 (I p < 0.05); Tilt 1 x Supine 1 (J p < 0.05).
[Table 6] shows the LF/HF ratio of the spectral analysis comparisons during supine 1, tilt
1, supine 2, tilt 2 and supine 3 moments in the GC and PCOS group in women in both
groups with and without metabolic syndrome. There was no difference between the groups.
Tabela 6
Comparison of cardiac autonomic modulation by LF/HF ratio of spectral analysis in
the supine 1, tilt 1, supine 2, tilt 2, and supine 3 periods between control women
(CG) without Polycystic Ovary Syndrome (with and without Metabolic Syndrome) and women
with Polycystic Ovary Syndrome (PCOS) (with and without Metabolic Syndrome)
|
Position
|
CG
|
PCOS
|
Metabolic Syndrome (MS)
|
|
Without MS
n = (26)
n (%)
|
MS
n = (6)
n (%)
|
Without MS
n = (24)
n (%)
|
MS
n = (8)
n (%)
|
CG
n = (6)
n (%)
|
PCOS
n = (8)
n (%)
|
|
Supine 1
|
0.64 (0.07)
|
0.97 (0.33)
|
0.86 (0.10)
|
1.25 (0.38)
|
0.97 (0.33)
|
1.25 (0.38)
|
|
Tilt 1
|
2.64 (0.32)
|
2.10 (0.80)
|
5.51 (1.89)
|
3.00 (0.94)
|
2.10 (0.80)
|
3.00 (0.94)
|
|
Supine 2
|
0.56 (0.07)
|
1.27 (0.61)
|
0.75 (0.09)
|
1.81 (0.68)
|
1.27 (0.61)
|
1.81 (0.68)
|
|
Tilt 2
|
3.80 (0.50)
|
4.74 (1.53)
|
5.99 (0.81)
|
3.75 (1.20)
|
4.74 (1.53)
|
3.75 (1.20)
|
|
Supine 3
|
0.59 (0.06)
|
1.12 (0.61)
|
0.96 (0.13)
|
2.49 (1.14)
|
1.12 (0.61)
|
2.49 (1.14)
|
Abbreviations: CG, control group; MS, metabolic syndrome; PCOS, polycystic ovary syndrome.
The data are presented in mean and standard error.
Discussion
The present study suggests that there is a significant increase in sympathetic autonomic
cardiac modulation at different times and in different positions among women with
PCOS who underwent two consecutive tilt tests. Our spectral and symbolic analyses
of HRV were performed simultaneously in women with PCOS and were compared with those
of women with regular menstrual cycles. Similar to other studies, both groups showed
increases in sympathetic cardiac modulation after changes from the supine positions.[16]
[17] However, we noted that the responses to the position changes were different between
groups and moments.
At the time of bench press 1, there was no difference in the HRV indices between the
groups; however, in supine 2 and supine 3, the women with PCOS had greater sympathetic
autonomic cardiac modulations compared with those of the CG group. We observed that
the PCOS group had higher LF (%) and LF/HF ratio, and lower HF (%). At tilt times,
it was observed that this difference only occurred in tilt 1, and again, the PCOS
group demonstrated elevated sympathetic cardiac autonomic modulation compared with
the CG group, also due to the higher LF (%) and LF/HF ratio and lower HF (%). In fact,
this phenomenon is noteworthy, since the PCOS group, in addition to maintaining a
predominance of sympathetic cardiac autonomic modulation in relation to the CG during
tilt 1, maintained this predominance in the two returns to the supine position (supine
2 and supine 3).
This alteration of sympathetic autonomic cardiac modulation in women with PCOS may
be associated with higher serum concentrations of testosterone and fasting insulin,
as well as high FAI and HOMA-IR values. Although we did not perform a correlation
analysis, previous studies have reported that the increase in sympathetic cardiac
autonomic modulation in women with PCOS occurs due to endocrine-metabolic changes,
especially hyperandrogenism and insulin resistance, which are both prevalent in PCOS.[3]
[25] Through different tests of short-term HRV, the heart rate and standing blood pressure
response after deep breathing and isometric grip, Kuppusamy et al[26] found in women with PCOS an inverse relationship between insulin resistance and
the LF/HF ratio, and increased sympathetic autonomic cardiac modulation, reduced HRV,
and increased biochemical factors, including insulin and testosterone. Other researchers
have also found, similar to our results, an increase in sympathetic modulation in
women with PCOS; however, they measured HRV after a different test that was related
to mental stress.[27] More recently, in animal experimentation, the simple neonatal exposure to excess
androgens predisposed the animals studied to autonomic imbalance, due to an increase
in sympathetic tone. Excess androgen was also associated with cardiometabolic disorders.[28]
It is known that hyperandrogenism and insulin resistance are associated with increased
obesity and metabolic disorders,[2]
[6]
[7]
[28]
[29] and these changes, over time, can predispose patients to the development of cardiovascular
diseases.[16]
[26] Therefore, metabolic alterations such as obesity, diabetes, and visceral fat increase
are directly linked to autonomic imbalances, especially increases in sympathetic cardiac
autonomic modulation.[16]
[26]
[30]
[31] However, in our study, we did not observe differences in body fat distribution or
percentile between the PCOS group and the CG. In addition, although metabolic syndrome
(MS) is a confounding factor, as it may reduce HRV,[32] in our study we did not observe differences when assessing the LF/HF ratio in women
with and without MS. However, in the present study, the number of women analyzed with
MS is low compared with the others. Therefore, we suggest that further studies be
conducted to assess HRV in women with PCOS and MS.
The increase in cardiac sympathetic autonomic modulation in women with PCOS was found
in several studies,[3]
[16]
[26]
[31] which encouraged us to evaluate the response of these women to a second consecutive
tilt test, and to conduct two methods of analysis, one linear and one nonlinear. After
our analysis and comparison between the groups, only the spectral analysis showed
differences between them, with a greater sensitivity of the spectral analysis compared
with the symbolic analysis. However, when the intragroup evaluation was performed
at different moments and with changes in posture, it was observed that for both the
CG and PCOS groups, 0V and the 0V/2V ratio increased when the volunteers leaned to
maintain standing position, similar to LF (n.u.) and the LF/HF ratio, conferring to
these variables the postulation of sympathetic cardiac autonomic modulation measurements.
On the other hand, it occurred in an opposite way with the HF (n.u.), 2UV, 2LV, and
2V total, that is, they decreased as the volunteers tilted and maintained the standing
posture. This finding is consistent with the literature, since at rest there is a
predominance of parasympathetic autonomic cardiac modulation, with a reverse of this
predominance with changes to standing postures.[16]
[17]
In the intra-group analyses, we observed that cardiac sympathetic autonomic modulation
was higher in tilt 2 compared with tilt 1 in both groups, after detection of LF (%),
LF/HF ratio and HF reduction (%) in the CG group and 0V increase and 0V/2V ratio and
reduction of 2UV and 2V total in the PCOS and CG groups. However, as reported, on
returning to supine position 3, the PCOS group maintained a sympathetic predominance
compared with the CG. As previously mentioned, hyperandrogenism and insulin resistance
may have contributed to this response in the PCOS group.[16]
[25]
[26]
[31] Dutra et al[33] showed that there are important differences between the autonomic cardiac modulation
between men and women, with lower sympathetic modulation (lower LF) and higher parasympathetic
modulation (higher HF) in women compared with men. In view of this, we suggest that
women with PCOS exhibit a cardiac autonomic modulation response to the tilt test that
is more similar to that of men, with greater sympathetic heart modulation and lower
parasympathetic modulation compared with the CG women. This “masculinization” of the
cardiovascular system in women with PCOS has also been suggested by other authors.[33]
[34]
In our study, one of the objectives was to identify whether the response to a second
consecutive tilt test would promote modifications or adaptations in the cardiovascular
autonomic responses that might allow the PCOS group to show values similar to those
found in the CG. The literature shows that among people with autonomic alterations,
especially those with symptoms of vasovagal syncope, one of the forms of treatment
has been repeated tilt training, which could, in part, facilitate improved control
of autonomic cardiac modulation. In our study, despite repeating the test, we observed
that the increase in sympathetic modulation in the PCOS group persisted compared with
the control group on the bench press 3. Thus, the present study showed that repeating
the tilt test is not sufficient to alter the autonomic control among women with PCOS
similar to that observed in women without PCOS.
The present study was innovative in evaluating the effect of two tilt tests in women
with PCOS. However, it was limited because it was not randomized. Thus, we suggest
that future studies carry out the randomization process as well as investigate and
compare the effect of two tilt tests on other populations.
Conclusion
We conclude that women with PCOS had higher autonomic sympathetic cardiac modulation
even after a second tilt test, and no adaptation to this provocative test was observed.
In addition, we observed that the linear spectral analysis method was more sensitive
for identifying differences between the groups than the non-linear method of symbolic
analysis.
