(Circulation. 1995;92:773-777.)
© 1995 American Heart Association, Inc.
Articles |
Long-term (5-Year) Changes in HDL Cholesterol in Cardiac Rehabilitation Patients
Do Sex Differences Exist?
From the Section of Cardiology, Department of Internal Medicine, and Department of Health and Sports Science, The Bowman Gray School of Medicine and Wake Forest University, Winston-Salem, NC.
Correspondence or reprint requests to James G. Warner, Jr, MD, EdD, Section of Cardiology, The Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045.
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Abstract |
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Background It is unknown whether the benefits of a cardiac rehabilitation program on HDL cholesterol (HDL-C) are equally achieved in men and women. To study this, we compared changes in HDL-C and other lipids in a large group of men and women participating in a cardiac rehabilitation program for up to 5 years.
Methods and Results We compared changes in HDL-C and other fasting lipids in 553 men and 166 women participating in a cardiac rehabilitation program at baseline and then annually for up to 5 years. Patients exercised 3 days a week at 70% to 85% of their maximum heart rate predetermined by a symptom-limited treadmill test. Aerobic capacity was estimated in metabolic equivalents (METs), and percent body fat was determined by skin-fold measurements. Baseline HDL-C, LDL cholesterol (LDL-C), and total cholesterol were significantly higher in women, whereas the ratio of total cholesterol to HDL-C was lower. Although both men and women showed an increase in HDL-C after 1 year (10% and 7%, respectively), only the women's level continued to increase over 5 years (20% versus 5% for men, P=.03). The sex difference in change in HDL-C remained after adjustment for age and smoking. A nonsignificant trend toward a greater change in HDL-C in women existed after adjustment for baseline percent body fat and estimated METs. The change in the ratio of total cholesterol to HDL-C was also more favorable in women, with a 38% decrease over 5 years compared with a 14% decrease in men (P=.01). Total cholesterol decreased by 20% in women and 8% in men (P=.0001), whereas LDL-C dropped by 34% in women and 15% in men (P=.0001). There was no sex difference in change in triglycerides.
Conclusions Women with heart disease who participate in a cardiac rehabilitation program may achieve greater lipid benefits over longer periods of time than previously demonstrated in men.
Key Words: lipoproteins • cholesterol • rehabilitation
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Introduction |
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Several studies showed HDL cholesterol (HDL-C) to be inversely related to the risk of coronary artery disease.1 2 3 4 5 6 Furthermore, low levels of HDL-C are associated with a worse prognosis after myocardial infarction.7 8 Although a recent report by the National Cholesterol Education Program Expert Panel9 defined low HDL-C as <35 mg/dL, recent data suggest that women with HDL-C <50 mg/dL are at increased risk of coronary artery disease.10 Previous studies demonstrated an association between exercise and elevated HDL-C and increases in HDL-C during training in otherwise healthy individuals.11 12 13 14 A limited number of studies showed a favorable effect of exercise on HDL-C in cardiac rehabilitation patients.15 16 17 18 However, most of these studies had small numbers of subjects and short training periods and were conducted almost exclusively in men. It is unknown whether the short-term benefits of a cardiac rehabilitation program on HDL-C are equally achieved in men and women and whether the improvements can be maintained over an extended period. The purpose of this study was to compare changes in HDL-C and other lipids in a large group of men and women participating in a cardiac rehabilitation program for up to 5 years.
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Methods |
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Patients
Retrospective data were analyzed in 719 patients (553 men, 166 women) participating in the Wake Forest Cardiac Rehabilitation Program between January 1, 1988, and January 1, 1994. Although the majority of patients were referred after myocardial infarction, coronary artery bypass surgery, or percutaneous balloon angioplasty, a small number were referred with cardiomyopathies, stable angina, and multiple cardiac risk factors.
Exercise Protocol
Patients exercised 3 days a week, with each
session generally
involving 10 minutes of stretching followed by 30 to 40 minutes of
walking, jogging, or riding a stationary bicycle. Exercise intensity
was individually prescribed on the basis of baseline treadmill results
and was gradually increased to a goal of 70% to 85% of maximum heart
rate or maintained at a level below that which caused
symptomatic or silent ischemia. Each patient was
given individual dietary instruction for a low-cholesterol,
low-saturated-fat, and when appropriate weight-reducing diet. Dietary
goals were established at baseline and then monitored annually
throughout the study period. All patients were also counseled on stress
management.
Data Collection
Testing was performed at baseline, 3 months,
6 months, and 1
year and then annually. Plasma lipids, estimated metabolic
equivalents (METs), percent body fat, and body weight were assessed at
each testing session. All patients fasted for at least 12 hours before
blood samples were obtained. Lipid levels were measured in a Centers
for Disease Control standardized lipid laboratory (National Health
Laboratories, Winston-Salem, NC). LDL cholesterol (LDL-C)
was calculated with the Friedewald equation on the basis of measured
values of total cholesterol, HDL-C, and
triglycerides.19 In patients with a recent
myocardial infarction, baseline lipids were measured a minimum of 4
weeks after the event. All patients also underwent a symptom-limited
treadmill test with standard protocols. Blood pressure and 12-lead ECG
were monitored during each test. Exercise functional capacity was
estimated in METs on the basis of total exercise workload. Percent body
fat was estimated with the sum of three skin-fold
measurements.20
To determine whether there were differences between men and women for exercise compliance, use of ß-blockers, and use of lipid-lowering agents, a random sample of 20% of the cohort was examined by retrospective chart review. Exercise compliance was reported as the percentage of exercise sessions attended during months 3, 6, 12, 24, 36, 48, and 60, depending on the length of program participation. Women taking estrogen were also identified from this sample.
Statistical Methods
Baseline characteristics of the women and
men were compared by
use of nonpaired t tests and 
2
analysis. The change in each lipid parameter over 5
years for men and women were compared by use of a test for linear time
trends in a repeated-measures ANCOVA. All repeated-measures models were
adjusted for each individual participant in the cohort to prevent bias
caused by unequal follow-up. From a random subgroup, exercise
compliance was evaluated by use of a nonpaired t test; the
use of ß-blockers and lipid-lowering agents was compared by use of
2 analysis.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Baseline Characteristics
Table 1
shows the
baseline characteristics for men
and women. Age, visits per subject, follow-up length, and smoking
status were similar in both groups. Women had a higher percent body fat
and lower estimated METs at baseline compared with men. HDL-C, LDL-C,
and total cholesterol were significantly higher in women,
while the ratio of total cholesterol to HDL-C was lower.
Triglyceride levels were similar in both groups despite
baseline differences in HDL-C.
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Rehabilitation Effects
Our primary objective in this study
was to determine whether a sex
difference existed with regard to changes in HDL-C after participation
in a cardiac rehabilitation program. Both men and women showed an
increase in HDL-C after 1 year (10% and 7%, respectively). However,
men demonstrated little or no increase in HDL-C relative to baseline
after 1 year, while HDL-C in women continued to increase over 5 years
(P=.03; Fig 1). The percent increase in HDL-C
after 5 years relative to baseline was 20% for women compared with 5%
for men. The ratio of total cholesterol to HDL-C revealed a
similar trend in the opposite direction, so that after 5 years there
was a 38% decrease for women and a 14% decrease for men
(P=.01; Fig 2).
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Table 2
gives the remainder of the lipid
parameters. There were sex differences over time for both
LDL-C (P=.0001) and total cholesterol
(P=.0001). Over 5 years, LDL-C decreased by 34% in women
and 15% in men, while total cholesterol declined by 20%
in women and 8% in men. There was no sex difference in
triglycerides over the training period.
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Table 3
illustrates the effect of sex on change in HDL-C
after adjustment for other baseline determinants of HDL-C. A
statistically significant sex difference remained after separate
adjustments for age and smoking. A nonsignificant trend toward a
greater change in HDL-C in women was evident after adjustment for
baseline percent body fat and METs. When all variables were
included in the statistical model, no sex difference with respect to
change in HDL-C was found. The relation between change in HDL-C and
change in these other variables during participation in the
rehabilitation program will be the subject of a separate report.
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To examine the possibility that increased HDL-C in women was related to better exercise compliance, we analyzed data on a 20% random sample of the entire cohort. From the sample, attendance data were available for 56 men and 18 women. There was no difference in mean percent compliance between the two groups (70% for men versus 68% for women). Data on the use of ß-blockers and lipid-lowering agents were more consistently available from this sample (111 men, 33 women). There was no difference between the groups for use of ß-blockers (48% of men versus 36% of women) or lipid-lowering agents (17% of men versus 22% of women). Only 2 of 33 women (6%) were on estrogen replacement therapy.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The results of our study show that a sex difference exists with respect to changes in HDL-C during participation in a supervised cardiac rehabilitation program. In our patient population, men showed a 10% increase in HDL-C after 1 year, but over the next 4 years, there was no further increase. In contrast, women began with a significantly higher baseline HDL-C, but levels continued to rise from 7% at 1 year to 20% (mean, 56.1 mg/dL) at 5 years. There were also significantly greater improvements in the ratio of total cholesterol to HDL-C, LDL-C, and total cholesterol in the women compared with men.
A limited number of observational studies and clinical trials compared men and women in cardiac rehabilitation programs. In one of the few studies comparing the lipid effects of cardiac rehabilitation between men and women, Cannistra et al21 did not find statistically significant improvements in any lipid parameter in either sex despite significant increases in aerobic functional capacity in both men and women. While the exercise intensity in their study was comparable to that in this study, the program continued for only 12 weeks. Other exercise studies that demonstrated significant improvements in HDL-C in patients with cardiovascular disease had longer periods of follow-up, ranging from 3 to 12 months.16 18 22 However, these studies were conducted almost exclusively in men. The current study confirms a benefit of exercise on HDL-C in both men and women after 12 months but also extends these observations by demonstrating that women may continue to derive additional benefits over longer periods of exercise up to 5 years.
It is well known that patients with HDL-C <35 mg/dL have a higher risk of developing significant coronary artery disease.5 7 8 23 Because most of the data were derived from male subjects, it is unknown whether this cutoff point is equally appropriate in women. Bass et al,10 in a large study evaluating the role of HDL-C as a cardiovascular disease risk factor in women, found that women with HDL-C <50 mg/dL had nearly a threefold increase in mortality risk because of cardiovascular disease. Other studies support an increased risk of cardiovascular disease in women with HDL-C >35 mg/dL and <50 mg/dL.1 23 The women in the present study began with a baseline HDL-C <50 mg/dL; thus, they were in a higher-risk group. Significantly increasing HDL-C, as occurred in women in this study over a 5-year period, may reduce the risk of future morbidity and mortality from cardiovascular disease. This issue will need to be addressed through further research.
It is unclear why HDL-C remained essentially unchanged after 1 year in men and continued to rise over 5 years in women. The women began the study with lower estimated METs and a higher percent body fat compared with men. There may be a potential for greater benefit for women in cardiac rehabilitation programs because they begin with a lower functional capacity and a less favorable body composition. Cannistra et al21 showed that women participating in a cardiac rehabilitation exercise program for 12 weeks increased their peak METs by 30% compared with a 21% increase in men. A negative correlation between percent body fat or body weight and HDL-C was demonstrated in premenopausal11 and postmenopausal24 women and in men.25
The Framingham Study found a strong association between patients having a ratio of total cholesterol to HDL-C ratio >4.5 and coronary artery disease.26 27 Furthermore, the ratio of total cholesterol to HDL-C has been shown to be independently related to the severity of angiographically determined coronary artery disease in women.28 29 Exercise training in patients with coronary artery disease can significantly reduce the ratio of total cholesterol to HDL-C, thus potentially reducing the risk of subsequent cardiovascular events.16 17 18 22 In this study, a significant sex difference was present for the mean ratio of total cholesterol to HDL-C. Women showed improvement in the ratio over 5 years, whereas most of the improvement in the men occurred during the first year. Because it appears that women with HDL-C levels <50 mg/dL are at increased risk of cardiovascular disease, it may be that the lower baseline ratio of 5.6 in women may be as much of a risk as or a greater risk than the higher baseline value in men.
Significant sex differences also occurred for LDL-C and total cholesterol, with the change over time being more favorable in women. Baseline total cholesterol and LDL-C were significantly higher in women, which may have allowed greater improvement over time. Higher baseline levels of total cholesterol and LDL-C in women compared with men were similarly demonstrated in female participants in the Lipid Research Clinics' Follow-up Study10 and in a comparison study of men and women in a cardiac rehabilitation program.21 A sex difference in change in triglycerides was not detected. Some epidemiological studies found triglycerides to be predictive of coronary heart disease in women30 and to be inversely associated with HDL-C.31 Studies of patients with coronary heart disease who undergo exercise training demonstrated significant increases in HDL-C despite a lack of change in triglycerides.16 17
When baseline variables that are related to HDL-C, such as percent body fat and estimated METs, were adjusted for, the sex differences were slightly diminished. As indicated earlier, the significantly lower baseline percent body fat and estimated METs in women may have allowed more benefit from the cardiac rehabilitation program over time. However, a strong trend toward statistical significance remained, which suggests that these two variables accounted for only a small portion of the sex difference.
Study Limitations
Although this study examined a large number
of patients at
baseline, relatively few subjects were followed for the maximum of 5
years, thus introducing the possibility of significant survival bias.
Nonetheless, 83 subjects had at least 5 years of follow-up and a total
of 900 person-years of observation, making this one of the largest
cardiac rehabilitation observational studies to examine the effects of
exercise on HDL-C and other lipids. Furthermore, appropriate
statistical methods were used to adjust for variable length of
follow-up and to prevent a survival bias from influencing the
results.
The original data collection for this study did not include information on certain variables that could influence changes in HDL-C, such as compliance to the exercise program or use of ß-blockers, lipid-lowering agents, or hormone replacement therapy. However, data retrospectively collected on a 20% random sample of the cohort provided no evidence that these variables could have accounted for the more favorable changes in HDL-C observed in women compared with men. No data were available on alcohol consumption. Finally, we did not adjust for dietary intake at baseline. While dietary change could have altered LDL-C or total cholesterol, there is little, if any, dietary effect on HDL-C.32
Conclusions
These data suggest that women with heart disease
may derive even
greater lipid benefits over longer periods of time from cardiac
rehabilitation than was previously demonstrated in men. This has
potentially important implications for guidelines concerning the use of
exercise as a nonpharmacological intervention for secondary prevention
of heart disease in women with dyslipidemias. Future
studies are required to confirm these observations and to clarify the
mechanism through which exercise affects HDL-C and other lipids in
women and men.
Received February 1, 1995; accepted February 21, 1995.
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