In 2004, heart disease moved from being the third leading cause of death in Taiwan to the second, causing 36 deaths per day.1 Although the public stereotype of coronary heart disease (CHD) is that of a disease affecting primarily men,2 the American Heart Association has reported that, since 1984, the mortality rate for heart disease has been higher in women than in men.3 In 2003, women accounted for 53.1% of cardiac deaths, with 1 of every 3 women having a history of cardiovascular disease. Although the onset of symptoms of CHD is typically 10 years later in women than in men, the disease in women is typically more severe.4 The American Heart Association has reported that there is a 3-fold increase in the morbidity from CHD in postmenopausal compared with premenopausal women, suggesting a correlation between the increasing severity of the disease in this age group and declining estrogen levels.2,5 Coronary heart disease is thus a significant health issue for perimenopausal and postmenopausal women.
Heart rate variability (HRV) refers to variation in the beat-to-beat (RR) interval and is an important indicator for the regulation of the cardiovascular system by the autonomic nervous system (ANS).6,7 Heart rate variability is broken down into a number of constituent parameters, each of which corresponds to the functioning of a different portion of the ANS: the high-frequency (HF) component mainly reflects parasympathetic nervous activities; low frequency (LF) reflects chiefly sympathetic and a fraction of parasympathetic nervous activities, whereas total power (TP) represents overall ANS activity. The ratio of LF to HF power serves as an index of sympathovagal balance.8 Abnormal activity of the ANS, particularly an increase in sympathetic and decrease in parasympathetic activity, has been reported to increase mortality in cardiovascular disease.9 Accordingly, studies have indicated that not only can changes in HRV be diagnostic for the presence of cardiovascular disease, but also the degree of decrease in HRV during acute myocardial infarction (AMI) can be used to predict mortality and arrhythmic complications.10,11
Recent studies have suggested that CHD patients can show a significant decrease in HRV even in the absence of other complications.12 Bedridden CHD patients have lower HRV compared with age-matched healthy individuals. However, CHD patients who can perform regular activity have HRV that is similar to that of healthy individuals.13 Heart rate variability normally decreases in menopausal women,14 even those who engage in physical activity. However, women who perform dynamic physical activity have greater HRV than women who perform static physical activity, both before and after menopause.15
Although a number of studies have revealed that aerobic exercise is effective in improving the HRV of CHD patients,16-18 they have typically included few women.19 Thus, given the well-documented sex-based differences in HRV, whether the results of the previously mentioned studies can be applied to postmenopausal women requires further exploration. Additionally, those studies were based on institutional exercise training programs, which tend to be inconvenient or difficult for participants to attend, in contrast to a program that can be carried out at home. Regular aerobic exercise also has the benefit of improving functional capacity (FC), and a significant relationship between FC and future cardiovascular disease risk has been reported.20 Therefore, the purpose of this study was to design a home-based exercise program and to test its ability to improve both the FC and HRV of postmenopausal women with CHD.
Subjects were postmenopausal women with CHD who had been recruited from the cardiology outpatient department of a medical center in northern Taiwan. Inclusion criteria were, first, that the patient was younger than 75 years and had experienced menopause at least 1 year previously. Second, included patients needed to have been diagnosed with CHD and to meet each of the following criteria: (1) more than 70% inner-diameter stenosis of at least 1 coronary artery or more than 50% stenosis of the left coronary artery, (2) a history of AMI treatment with percutaneous transluminal coronary angioplasty or coronary artery bypass graft after AMI, (3) a left ventricular ejection fraction greater than 50%, or (4) able to walk, with no muscular or skeletal limitation.
The exclusion criteria included (1) having arrhythmia, (2) having a blood pressure greater than 160/90 mm Hg at rest, (3) being on menopause due to hystero-oophorectomy, (4) having other uncontrolled chronic diseases, and (5) if they had undergone regular moderate exercise more than twice a week within 6 months of the study enrollment period.
This study used a quasi-experimental design, in which study participants were screened and recruited by physicians in the study hospital's cardiology outpatient department. Permission was obtained from the institutional review board of the hospital. The researcher explained the purpose of the study as well as what they could expect from the procedures that were to be used. After written informed consent was obtained from the participant, the first HRV measurements, at rest and during a 6-minute walking test (6MWT), were measured.
The experimental group received guidance in how to perform the home-based exercise program and how to record relevant information for each activity, whereas the control group received no such instruction. The effect of the home-based exercise program was evaluated after 8 weeks by performing a second set of FC and HRV tests.
Home-Based Exercise Training Program
The 8-week, home-based exercise program comprised 3 sessions per week, with each session consisting of a 5-minute warm-up of slow walking, a brisk-walking exercise segment, and finally a 5-minute cooldown of slow walking. During the brisk-walking segment, participants were required to reach between 13 and 15 on the Borg Scale. When this goal could be reached on 3 consecutive thrice-weekly sessions, without symptoms such as chest tightness, dizziness, or palpitation, the duration of the brisk-walking segment was increased. Once patients were able to comfortably walk briskly for 30 minutes, they continued at this level for the remainder of the 8-week period.
We designed a brochure to educate participants on the benefits and risks of the home-based exercise program, the use of the Rating of Perceived Exertion scale, and how to maintain a daily log of exercise time. The brochure also explained how to carry out the pre-exercise self-evaluation, as well as how to manage a range of potential adverse symptoms that might arise during exercise. An emergency phone number was included for patients encountering adverse symptoms for the first time. Patients received a follow-up phone call immediately after beginning the program, when they were asked whether they had any difficulty carrying out or recording their activity. One week later, a second follow-up phone call was made. If problems regarding the home-based exercise program could not be solved over the telephone, a researcher met with the participant immediately and provided direction.
During the home-based exercise program, follow-up phone calls were made at least once a week, both to gather information and to encourage the participant to continue with the exercise. During the fourth week, a researcher met with the participants to discuss the implementation process and review their records.
Measurement of HRV
The BIOPAC system (model MP 150 WSW, BIOPAC System, Inc, Goleta, CA) was used for electrocardiogram (ECG) recording, with the ECG measurement converted to a digital signal using ACK100W (BIOPAC System, Inc, Goleta, CA) software for the analysis of HRV. The HRV analysis software was used in the autonomic nervous function spectrum analysis mode (power spectral analysis) to detect the R wave. After the R waves were reviewed, premature contractions of atria and ventricles were excluded, and the length of the PR interval was calculated to obtain frequency parameters. Frequency-domain analyses of HRV were carried out according to the recommendations by the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.8 Power spectral density was computed by fast-Fourier transformation and was integrated by 0.04 to 0.15 Hz, 0.20 to 0.30 Hz, and 0.00 to 0.50 Hz, respectively, to obtain the LF (ms2), HF (ms2), TP (ms2), and LF/HF ratio. The powers of these frequency components were expressed as the natural logarithm of the absolute value, and the power of the LF and HF also was expressed as a normalized unit (LF nu and HF nu), which was calculated by dividing the power by the TP minus power below 0.03 Hz.
Heart rate variability in this study was measured at rest, as participants lay down for 10 minutes in quiet environment, and only the ECG data from the final 5 minutes were used for analysis. Clear explanations were given to participants before data collection in a quiet treatment room to allow them to become comfortable with equipment and activities taking place. To prevent the HRV measurement from being affected by extraneous factors, all data were collected in the morning, whereas participants' respiratory rate was controlled between 12 and 20 times per minute, room temperature was kept between 22°C and 25°C, and humidity was kept between 40% and 50%. Electrocardiographic data were collected immediately after the ECG monitoring equipment was applied and before the home-based exercise began. When the test was completed, collected data were transferred to the computer for HRV analysis.
Six-Minute Walking Test
As a measurement of the aerobic power and cardiovascular endurance of the subjects, the FC was tested using a 6MWT, designed according to the guidelines proposed by Guyatt et al,21 which has been demonstrated to provide valid and reliable data regarding an individual's physical FC.22 In this test, the participant was asked to walk as far and as quickly as he/she could on a 100-ft flat surface. Participants were allowed to slow down or to take a short break during the test. They were requested not to talk during the test and were reminded of this again 1 minute before the test ended. When the test was completed, the longest distance traversed over the 6-minute period was recorded.
SPSS version 15.0 software (SPSS Inc, Chicago, IL) was used for data analysis. The significance level α was defined as .05. Statistical methods included the χ2 test and t test for the analysis of similarity between 2 groups, the paired t test for before-and-after comparisons within each group, the independent t test for between-group comparison, and 2-way analysis of variance (ANOVA) for determination of the effectiveness of home-based exercise program on the improvement of FC and HRV of postmenopausal women with CHD.
Each of the 40 participants was given the choice to join either the experimental or control group. In the experimental group (n = 21), 5 participants were unable to complete the test because of knee pain or family issues or because they moved. In the control group (n = 19), 3 participants did not complete the test because of physical discomfort or because they traveled abroad. Thus, there was a final total of 32 participants in the study, 16 in each of the experimental and control groups, with an attrition rate of 20%. The demographic characteristics of the 8 missing subjects were not significantly different from those who remained in the study.
Most participants were married (n = 28, 87.5%), unemployed (n = 28, 87.5%), and aged between 55 and 74 years (65.44 [SD, 5.62] years) and had received education for 4.59 (SD, 3.96) years. Their average age at menopause was 50.41 (SD, 3.40) years, and their mean body mass index was 26.64 (SD, 4.05) kg/m2. Eighteen participants (56.25%) had a history of diabetes, 5 were taking hormone medications (15.63%), 10 were taking β-blockers (31.25%), and 4 were taking an angiotensin-converting enzyme inhibitor (12.50%). There were no significant differences in the demographic characteristics of the 2 groups (Table 1).
All subjects in the experimental group completed at least 18 of 24 potential exercise sessions in 8 weeks, yielding an average compliance rate of 89.37%. As shown in Table 2, the mean endurance of both groups increased significantly after completing the home-based exercise program (P < .05), but the experimental group had a significantly greater increase than did the control group (41.86 vs 9.18 m, P < .05; Table 3). Two-way ANOVA indicated no interaction effect between group and testing time (F = 0.992, P = .323). However, a group main effect (F = 6.954, P = .011) was identified based on the similar walking distance of the experimental and control groups in the first week compared with an observable difference in the eighth week (427.03 vs 367.42 m).
When HRV parameters were reassessed after completion of the 8-week exercise program, TP, HF (ms2), LF (ms2), and HF (nu) were all found to be significantly increased in the experimental group (P < .05). The control group showed no significant change in these parameters (Table 2). As shown in Table 3, when the 2 groups were compared, a significant difference was observed in the degree improvement of TP, HF, and LF (165.25 vs −107.24 ms2, 91.0 vs 3.07 ms2, and 48.13 vs −17.67 ms2 for the experimental and control groups, respectively). Analysis by 2-way ANOVA showed both a group-and-time interaction effect on TP (F = 4.719, P = .034). Whereas the group main effect had shown no significant difference in the first week (F = .290, P = .594), TP values of the experimental group were significantly greater than control values on the eighth week (F = 7.245, P = .012) (Figure 1).
Analysis of HF data (ms2) showed both a group-and-time interaction effect (F = 5.724, P = .020) and a group main effect (F = 7.656, P = .010). Although there was no significant difference between the 2 groups on the first week, HF values for the experimental group were significantly greater than control values on the eighth week (F = 7.656, P = .010). The experimental group showed a significant difference in HF between the first and eighth weeks (ms2; F = 7.343, P = .011), whereas this comparison showed no significant difference for the control group (Figure 2).
As seen with TP and HF, LF (ms2) showed both a group-and-time interaction effect (F = 4.630, P = .036) and a group main effect. Although no significant difference in LF was observed between the 2 groups in the first week (F = 5.707, P = .024), the mean LF of the experimental group was significantly greater than control values on the eighth week. The time main effect was seen based on the observation that the LF of the experimental group on the eighth week was significantly greater than that on the first week (F = 4.834, P = .036), whereas no corresponding difference was seen in the control group.
Neither HF (nu), LF (nu), nor the LF/HF ratio showed either a group or time interaction effect (Figure 3).
The main finding of this study was that an 8-week home-based exercise program improved FC and HRV in postmenopausal women with CHD. The average age of participants was 50.4 (SD, 3.4) years. This was similar to a Taiwanese study in which the average age of Taiwanese menopausal women was 48.4 (SD, 3.8) years.23 Most participants were unemployed (n = 28, 87.5%). This may have been because the study design required subjects to exercise at home 3 times per week, which may have been difficult for working individuals to schedule. The average body mass index of the participants was 26.64 (SD, 4.05) kg/m2, a value much higher than the average of 24.6 to 24.8 kg/m2 for 65-year-old Taiwanese women in the general population. This may have been because most participants in this study had a low degree of physical activity and did not regularly exercise and that their CHD may have further limited the type of physical activity they could perform.
One of the goals of the study was to explore the effect of home-based exercise on the improvement of FC in postmenopausal women with CHD. We found that the average distance completed by all participants in the study in the 6MWT was 371.70 (SD, 66.17) m, a distance considerably less than that reported by Li,24 390.52 (SD, 95.44) m, for participants of average age 54.32 (SD, 11.13) years. The difference between the 2 studies might be attributable to the higher average age of the participants in our study, as FC has been reported normally to peak at age 25 years and thereafter to decline 1% per year.25 Enright and colleagues26 also tested the 6-minute walking distance of healthy women of average age of 68 years and found an average distance of 367 m, a figure similar to our results. Although our participants were younger, on average, than those of Enright et al,26 they were also postmenopausal with CHD, which could conceivably have an impact on their FC.
After 8 weeks of home-based exercise, participants in the experimental group had increased their 6-minute walking distance more than did those in the control group (10.9% vs 2.5%). This supported the hypothesis that exercise training could effectively improve the FC of postmenopausal women with CHD. Although Kirwan et al27 also demonstrated that walking exercise training of 5 days per week for 26 weeks improved FC in postmenopausal patients with CHD, their study methodology differed from ours in using maximal instead of submaximal oxygen consumption to measure the subject's FC. However, a previous study reported that V˙O2peak during the 6MWT did not differ from the values obtained during a symptom-limited exercise test.28 Belardinelli et al29 reported that moderate exercise training 3 times weekly for 8 weeks improved peak oxygen consumption (V˙O2peak) by 18% in patients with chronic heart failure. Fiorina et al30 examined the improvement of FC after a cardiac rehabilitation program by applying the 6MWT in 348 patients who had undergone cardiac surgery. The results showed that after 15 (SD, 3) days of an in-hospital rehabilitation program, the walking distance of these patients increased significantly, from 281 to 411 m.
Monmeneu et al31 reported that the FC of heart disease patients declined in parallel with decreasing HRV. Pardo and colleagues18 further reported that when the FC of participants increased to a level of 1.5 MET (metabolic equivalent), their HRV (TP and HF) increased significantly. In contrast, we found no significant correlation among the different indicators of HRV and the 6MWT. One explanation for this difference is that most of the previous studies used V˙O2max as an indicator of FC test, whereas we used the distance covered during the 6MWT. Although a high correlation coefficient between FC and the 6-minute walking distance had been reported,32 in our study the speed of fast walking was determined by the participants. Therefore, the actual measurements might have been affected by the participants' subjective attitude and motivation on the day. Thus, FC could not be measured as precisely as when tested on a treadmill or bicycle, and this may have masked some significant correlations during the test period.
In our subjects, the HRV indexes TP, HF (ms2), LF (ms2), and LF/HF (nu) were lower than those of both healthy individuals of average age 56.81 (SD, 11) years33 and of postmenopausal women.34 Therefore, postmenopausal women with CHD appeared to exhibit poorer regulation of the ANS than do either healthy or postmenopausal women. Wennerblom and colleagues12 reported that CHD patients have a lower HRV due to an increase in sympathetic nervous activity and a decrease in parasympathetic activity. They further reported that such a disorder of ANS regulation was able to evoke ventricle fibrillation, which was sometimes fatal.
Another focus of this study was the effect of a home-based exercise program on HRV in postmenopausal women with CHD. Results indicated that the TP, HF (ms2), and LF (ms2) parameters of HRV improved significantly, whereas LF (nu) and the LF/HF ratio did not. This finding suggests that exercise training has a beneficial effect on parasympathetic nervous activity in this patient population. A similarly dramatic improvement in TP and HF (ms2) was reported for healthy individuals who underwent a program of intense endurance exercise (85% HRmax), 25 minutes per day for 6 weeks.35 Other studies reported that, in young men subjected to aerobic exercise 8 times a week for 2 weeks, there was a direct effect on improving the parasympathetic regulation of the cardiac system.36 Further studies have indicated that an increase in parasympathetic nervous activity can be attributed to the adaptation of the peripheral and central nervous systems during an aerobic exercise training regimen lasting 6 months.37
Our results also indicated that the LF (ms2) of the experimental group had increased dramatically after 8 weeks of a home-based exercise program. Although LF (ms2) is known to be affected by the activity of both the sympathetic and parasympathetic nervous systems, we failed to see a significant change in LF (nu) (an indicator of sympathetic activity), and thus, we believe that the increase in LF (ms2) was directly related to an increase in parasympathetic activity. Our failure to see an effect on sympathetic activity is in contrast to previous reports indicating that, for CHD patients, 6 months of endurance training was effective in decreasing sympathetic nervous system activity.38 This difference might be explained by the relatively comparatively short length of our 8-week exercise program.
Finally, we found that, using a home-based exercise program, the SD of the RR interval of HRV had improved for 26.1%. This finding was consistent with previous reports that the SD of the RR interval of men with CHD increased 26% after taking 30 minutes of biking exercise for a total of 24 times in 2 weeks.39
The first limitation of this study lay in the requirement that participants have sufficient space and time for the home-based exercise program, which likely excluded some potential subjects. In addition, patients were allowed to choose whether they wanted to join the experimental or control group, which could have skewed the results. In addition, the home-based exercise program was implemented for only 8 weeks. Although we saw an improvement in HRV parameters related to parasympathetic activity, had the program been extended we might have seen an effect on sympathetic regulation of the cardiac system. We suggest further longitudinal studies be conducted to resolve this issue.
Summary and Implications
The results of this study support the hypothesis that a home-based exercise program is effective in improving FC and HRV in postmenopausal women with CHD, with the advantages that it can be continued for as long as the patient wishes, can be carried out on the patient's own time, and does not require travel.
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Keywords:Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved
coronary artery disease; functional capacity; heart rate variability; home-based exercise program; postmenopausal women