© 1995 American Heart Association, Inc.
Articles |
Hemostatic, Metabolic, and Androgenic Risk Factors for Coronary Heart Disease in Physically Active and Less Active Postmenopausal Women
From the Departments of Kinesiology (E.T.S., K.P.D., D.R.S.) and Medicine (Cardiology) (D.R.S.), University of Colorado, Boulder.
Correspondence to Edith T. Stevenson, PhD, University of Colorado, Department of Kinesiology, Campus Box 354, Boulder, CO 80309.
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Abstract |
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Abstract Physically active postmenopausal women have a lower incidence of coronary heart disease (CHD) than their more sedentary peers, but little information is available concerning the responsible mechanisms. The primary aim of this study was to test the hypothesis that physically active postmenopausal women demonstrate more favorable levels of hemostatic, metabolic, and androgenic CHD risk factors than less active control subjects. If so, a secondary aim was to determine which of the characteristics associated with a physically active lifestyle, ie, low body fat, a high-carbohydrate/low-fat diet, high maximal aerobic capacity (aerobic fitness), and high levels of physical activity, are most closely related to this lower risk profile. To address these aims, we compared CHD risk factors in physically very active women (n=14; age, 55±2 years) with those in healthy, nonobese sedentary control subjects (n=17; age, 56±1 years). Maximal aerobic capacity (fitness) was 83% higher (P<.001) in the physically active women. Concentrations of plasminogen activator inhibitor type 1 activity and tissue plasminogen activator antigen were lower (more favorable) (P<.005) in the physically active women versus control subjects, whereas plasma fibrinogen levels did not differ. The physically active women had lower (P<.01) fasting plasma insulin and glucose concentrations as well as smaller responses to an oral glucose challenge. Both total-body and abdominal fat levels were lower (P<.001) and lipid and lipoprotein profiles were generally more favorable (P<.05) in the physically active women. Plasma sex hormone–binding globulin concentrations were higher (P<.01) in the physically active women, indicating a lower androgenicity-related CHD risk. In addition, the physically active women consumed a diet that was higher (P<.002) in carbohydrates and lower (P<.02) in fat and protein. Stepwise multiple regressions indicated that although a portion of the observed variability in these CHD risk factors can be explained by physical activity levels per se, the associated differences in total body and abdominal fat, dietary composition, and aerobic fitness also contribute in a significant but selective manner. Thirty percent to 40% of each group were on hormone replacement therapy, but its effects appeared to be minimal. These results demonstrate that physically active postmenopausal women exhibit favorable levels of hemostatic, metabolic, and androgenic CHD risk factors, which could contribute to their lower incidence of CHD.
Key Words: aging • coronary heart disease • exercise • risk factors
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Introduction |
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Cardiovascular diseases (CVD), especially coronary heart disease (CHD) and cerebrovascular disease, are the leading causes of death, as well as morbidity and disability, in middle-aged and older American women.1 2 Recent estimates indicate that 1 in 9 women 45 to 64 years old has some form of CVD; after age 65 this ratio increases to 1 in 3 women.1 The health care costs associated with CVD in postmenopausal women alone have been estimated to exceed $11 billion per year.2 With the number of women
45 years old increasing annually, the societal
impact of CVD in this population will be even greater in the
future. Epidemiological data indicate that physically active postmenopausal women are at a lower risk of developing CVD in general and CHD in particular than their more sedentary peers.3 The mechanisms responsible for the lower CHD risk in physically active middle-aged and older women, however, have not been determined. Lower levels of total body fat and more favorable plasma lipid and lipoprotein profiles have been reported in physically active versus inactive postmenopausal women.4 5 6 7 8 However, little or no information is available on other CHD risk factors. Hemostatic factors, such as high levels of plasma fibrinogen, plasminogen activator inhibitor type 1 (PAI-1) activity, and tissue-type plasminogen activator (TPA) antigen, are associated with thrombosis,9 whereas other metabolic factors, such as elevated fasting plasma levels of glucose and insulin, glucose intolerance,10 11 high levels of abdominal fat, and high androgenicity (as reflected by low levels of sex hormone–binding globulin [SHBG]),12 13 are associated primarily with atherosclerosis. Importantly, there are no data on all of these CHD risk factors in a single population of physically active and inactive postmenopausal women. This is critical in light of recent findings indicating that unfavorable levels of these factors tend to occur together and, as such, result in a substantially higher risk of CHD than when they occur individually.14 15 16
If physically active postmenopausal women demonstrate more favorable levels of some or all of these CHD risk factors, an important question concerning the role of physical activity levels per se remains unanswered. High levels of physical activity are associated with low levels of total body and abdominal fat, high aerobic fitness, and often a high-carbohydrate/low-fat diet. Each of these factors may affect risk factors independently of physical activity levels.
The primary aim of this study was to test the hypothesis that physically active postmenopausal women demonstrate more favorable levels of hemostatic, metabolic, and androgenic CHD risk factors than less active control subjects. If so, a secondary aim was to determine which of the characteristics associated with a physically active lifestyle, ie, low body fat, a high-carbohydrate/low-fat diet, high maximal aerobic capacity (aerobic fitness), and high levels of physical activity, are most closely related to this lower risk profile. To address these aims, we used a cross-sectional study design in which middle-aged and older (masters) female endurance athletes were compared with age-matched, healthy, nonobese control subjects, similar to the experimental approach we used previously in men.17 18
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Methods |
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Subjects
Thirty-one healthy women participated in this study: 14 highly trained runners (55±2 years old, mean±SEM; range, 49 to 67 years) and 17 age-matched, minimally active control subjects (56±1 years old; range, 50 to 64 years). The runners were selected from age-group winners in a local, national-class road race. The control subjects were recruited from respondents to newspaper advertisements. The runners had been training for 18±2 years (range, 10 to 40 years); they ran 31±3 miles/wk (range, 20 to 46 miles/wk). Most of them (12 of the 14) supplemented their running with 1 to 4 weekly cross-training sessions (swimming, bicycling, pool running, tennis). The women in the control group did not follow any program of regular physical exercise.
All subjects were free of overt coronary artery disease, as assessed by
medical history, physical examination and by resting and maximal
exercise electrocardiograms. Of the 31 subjects, 30 were
postmenopausal, as indicated by plasma follicle stimulating hormone
(FSH) levels >40 IU/L.19 One of the runners was
experiencing menopausal symptoms, but her plasma FSH levels indicated
that she was not yet postmenopausal. However, because inclusion of her
data did not affect the mean values of the dependent variables of
interest, she was included in the study. Four of the 14 active women
(
30%) and 7 of the control subjects (40%) were on oral hormone
replacement therapy consisting of conjugated estrogen (Premarin, 0.625
mg/d) in combination with medroxyprogesterone acetate (Provera, 2.5
mg/d). None of the subjects smoked or took medications that could
affect any of the dependent variables. Group data on maximal oxygen
uptake (
O2max) and
vascular volumes have been reported elsewhere.20
The nature, purpose, and risks of the study were explained to each subject before written informed consent was obtained. The experimental protocol was approved by the Human Research Committee at the University of Colorado at Boulder. Procedures followed were in accordance with institutional guidelines.
Measurements
O2max was determined
with on-line computer-assisted open-circuit spirometry during
incremental treadmill exercise, as described previously.20
All anthropometric measurements were made by a single investigator
while the subject was in a standing position. Waist circumference was
measured at the narrowest part of the torso, and hip circumference was
measured at the maximal extension of the buttocks.21 Body
fat was estimated from the sum of skin folds measured at five body
sites.22 Estimated daily energy expenditure was assessed
by the Stanford Physical Activity Questionnaire.23 Daily
dietary intake and composition were assessed from analyses of 3-day
dietary intake records (Food Processor Plus, ESHA Research).
All measurements of blood-derived risk factors were performed in the clinical laboratory affiliated with the Clinical Research Center at the University of Colorado Health Sciences Center. Subjects reported to the Center between 7:30 and 9 AM after a 12-hour overnight fast and a 24-hour period with no strenuous physical activity. Upon arrival, each subject rested in a supine position while a catheter was inserted into an antecubital vein. After 20 minutes of supine rest in a quiet, semidarkened room (the typical procedure for basal measurements of these variables), 12 mL of blood was drawn for subsequent analysis of plasma levels of norepinephrine, fibrinogen, PAI-1 activity, TPA antigen, and FSH. Plasma norepinephrine concentrations were determined because of the postulated role of elevated sympathetic nervous system activity in syndromes associated with multiple risk factors.14 24 Plasma levels of PAI-1 activity were measured because it is known to inhibit fibrinolysis.9 Plasma concentrations of TPA antigen have been shown to be a risk factor for myocardial infarction and are associated with mortality in patients with CHD.25 26 Both of these factors are known to increase with age.27 Measurements of plasma TPA activity could not be obtained from the clinical laboratory. After 10 minutes in an upright sitting position (typically used for these measurements), 27 mL of blood was drawn to be analyzed for plasma lipids (total cholesterol [TC], HDL cholesterol [HDL-C], HDL3-C, and triglyceride [TG] levels), plasma SHBG concentrations, and fasting levels of plasma glucose and insulin. SHBG was determined to assess the level of androgenicity, which has been linked to syndromes associated with multiple risk factors14 24 28 ; low levels of SHBG reflect high androgenicity and vice versa.28 Because of the influence of estrogen on plasma SHBG levels, it was assessed only in those women who were not on hormone replacement. Immediately afterward, an oral glucose tolerance test was administered, as described in detail previously.17 Subjects ingested a standard glucose drink that contained 40 g glucose/m2 body surface area. Venous blood samples (5 mL each) were obtained 30, 60, 90, 120, and 180 minutes after glucose ingestion. Total areas under the concentration-time curves for plasma glucose and insulin were calculated by the trapezoid rule, in which only positive areas above fasting baseline levels were included, as described previously.17
Analyses
Conventional enzymatic methods were used to determine plasma TC
and TG.29 30 Plasma HDL-C and HDL3-C levels
were determined by the dextran precipitation technique31 ;
plasma HDL2-C was calculated as the arithmetic
difference between plasma HDL-C and HDL3-C. Plasma
LDL-C levels were computed by the Friedewald equation32
as TC-HDL-TG/5. Plasma glucose levels were determined
enzymatically33 and plasma insulin concentrations by
radioimmunoassay with polyethylene gel.34 The Clauss
method for clottable fibrinogen was used to determine plasma fibrinogen
levels.27 Plasma PAI-1 activity27 and TPA
antigen35 were determined by commercially available enzyme
immunoassay kits (Instrumentation Laboratories). A competitive
radioimmunoassay kit (Techland Sex Hormone Binding Globulin Kit, Wien
Labs Inc) was used to measure plasma levels of SHBG.36
Plasma norepinephrine levels were determined with a radioenzymatic
assay.37 A chemiluminescence immunometric assay kit was
used to measure plasma FSH levels (Nichols Institute
Diagnostics).38
Data Analysis
Differences in the dependent variables between the physically
active women and control subjects were assessed by a multivariate
analysis of variance (ANOVA). If a significant overall F (Wilks'
lambda) was found, a one-way ANOVA was then used to locate group
differences in each dependent variable. The significance level was set
at P<.05. Simple linear regression analysis was used to
assess relations between body fat and its distribution, diet,
O2max, physical
activity levels, hormone replacement, and the other dependent variables
of the study. In addition, stepwise multiple regressions were used to
assess the relative contributions of the physical activity–associated
characteristics to each of the CHD risk factors.
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Results |
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Physical Characteristics
The physically active women and control subjects were similar in age, height, casual blood pressure at rest, and estimated fat-free mass, but body weight, body mass index, and resting heart rate were lower (P<.001) in the active women (Table 1
). In addition, estimated daily energy expenditure and
O2max, both relative
to body weight, were higher (P<.001) in the active
women.
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Hemostatic Factors
Plasma fibrinogen levels were similar in the two groups
(P=.41) (Table 2). However, plasma
concentrations of PAI-1 activity and TPA antigen were 67% and 44%
lower (P<.005), respectively, in the physically active
women relative to the control subjects.
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Plasma Glucose and Insulin
Fasting plasma glucose (4.5±0.1 versus 5.2±0.1 mmol/L) and
insulin (39±1 versus 49±4 pmol/L) levels were lower
(P<.01) in the active women relative to the control
subjects (Figs 1 and 2). The increases in
plasma glucose and insulin concentrations were smaller in the active
women (P<.001) at each measurement point in response to the
oral glucose challenge, and both the attainment of peak concentrations
and the return to or below fasting levels were more rapid. Moreover,
the areas under both the glucose and insulin concentration-time curves
were smaller (P<.001) for the active women.
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Body Composition and SHBG
Sum of skin folds and estimated percent body fat were 59% and
49% lower (P<.001), respectively, in the physically active
women relative to the control subjects (Table 3). In
addition, the active women had smaller (P<.001) waist
circumferences, although there was no difference in waist-to-hip ratios
between the two groups. Plasma SHBG levels were 83% higher
(P<.01) in the active women.
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Plasma Lipids
There were no significant intergroup differences in plasma TC,
although the physically active women tended to have lower
(P=.13) levels (Table 4). Plasma total HDL-C
tended to be higher (P=.09) and LDL-C levels lower
(P=.10) in the active women versus control subjects. The
active women had 150% higher (P<.002) levels of plasma
HDL2-C and lower (P<.004) levels of
plasma TG. The atherogenic indexes TC/HDL-C and
TC/HDL2-C were lower and HDL-C/LDL-C higher for the
active women (all P<.05).
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Dietary Intake
Total estimated daily caloric intake was similar for the two
groups (1926±101 versus 1856±115 kcal, physically active women versus
control subjects), but dietary composition differed. The percentages of
protein and fat in the diets of the active women were significantly
lower (P=.02) than those for the control subjects (13±1%
versus 16±1% for protein; 23±2% versus 30±2% for fat), whereas
carbohydrate intake was significantly higher (P=.002) for
the active women (63±2% versus 54±1%). Dietary sodium intake was
marginally lower (P=.07) for the active women relative to
the control subjects (2165±163 versus 2660±192 mg/d), whereas sodium
excretion and urinary sodium concentrations did not differ. In
addition, alcohol and caffeine consumption was similar for the two
groups.
Plasma Norepinephrine Level
Supine levels of plasma norepinephrine were similar in the two
groups at rest (2.07±0.15 nmol/L for the physically active women
versus 2.28±0.17 nmol/L for the control subjects;
P=.39).
Influence of Hormone Replacement Therapy
To determine whether hormone replacement confounded the
interpretation of differences between the physically active women and
control subjects, the two subject groups were reanalyzed with the data
from the 11 hormone replacement users (4 active women and 7 control
subjects) excluded. The group differences discussed above were
unchanged when only the non–hormone replacement data were examined. To
test for a possible interaction between training status and hormone
replacement, a multivariate ANOVA was performed on the dependent
variables of the study; no significant interactions were found. To
further examine the influence of hormone replacement independent of
training status, the dependent variables were compared for the group of
hormone replacement users (n=11; 4 active women and 7 control subjects)
versus the group of nonusers (n=20; 10 active women and 10 control
subjects). The only significant difference between the two groups was a
lower level of TPA antigen in the users of hormone replacement
(3.0±0.4 versus 5.0±0.6 ng/mL, P<.02). In addition,
levels of fasting plasma insulin (3.9±0.4 versus 4.7±0.3 pmol/L,
P=.06) and PAI-1 activity (3.7±1.1 versus 7.8±1.6
arbitrary units/mL, P=.08) were marginally lower with
hormone replacement therapy.
Influence of Body Composition, Dietary Intake, Aerobic Fitness, and
Level of Physical Activity on CHD Risk Factors
Differences between CHD risk factors in physically active women
versus control subjects indicate that physical activity per se or some
other closely related characteristics (body composition, dietary
composition, and aerobic fitness) are associated with the favorable
risk factor levels observed in the active women (Table 5). Univariate correlations showed significant, although
primarily modest (R2 ranging from 12% to 49%),
relations between body composition (body mass index, estimated percent
body fat, and waist circumference), dietary composition (percentages of
fat, carbohydrate, and protein in the diet),
O2max, and the
hemostatic, metabolic, and androgenic CHD risk factors. The only
significant correlates of the level of physical activity were fasting
plasma glucose concentrations and the areas under the insulin and
glucose curves in response to an oral glucose tolerance test
(R2 ranging from 28% to 45%).
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The results of the stepwise regression analyses indicated that
abdominal fat (as estimated by waist circumference) and dietary
composition were key correlates of levels of hemostatic factors (plasma
PAI-1 activity and TPA antigen), plasma lipids and lipoproteins (HDL-C,
TG, LDL-C, and the atherogenic index, TC/HDL-C), and the area under the
insulin curve in response to an oral glucose tolerance test. Total body
fat (as measured by estimated percent body fat and body mass index) was
a primary determinant of levels of plasma SHBG and area under the
insulin curve. Percent dietary fat was the strongest predictor of
fasting plasma insulin concentrations.
O2max was a key correlate of
plasma HDL2-C concentrations and fasting glucose.
The only CHD risk factor that included physical activity as a
significant independent predictor was the area under the glucose curve
in response to an oral glucose tolerance test.
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Discussion |
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The primary finding of this study is that physically very active postmenopausal women exhibit a superior hemostatic, metabolic, and androgenic risk factor profile for CHD relative to healthy, nonobese, but less active women. More specifically, to the best of our knowledge this is the first study to demonstrate more favorable plasma levels of PAI-1 activity and TPA antigen, plasma glucose regulation, and plasma SHBG concentrations in physically active women and one of few studies to show lower levels of abdominal fat in this population. A unique feature is the documentation of superior levels of a number of CHD risk factors in a single population of physically active postmenopausal women. An important secondary finding of the study is that the more favorable CHD risk factor profile observed in this population appears to be related to their body fat distribution, dietary composition, and aerobic fitness as much as or more than to their high levels of physical activity per se. Taken together, our findings provide experimental support for the hypothesis that the lower incidence of CHD in physically active middle-aged and older women may be due, in part, to this advantageous risk factor profile.
Hemostatic Factors
Blood clotting and intravascular thrombus formation are important
in the development of acute coronary thrombosis.39 Plasma
levels of fibrinogen, PAI-1 activity, and TPA antigen play a central
role in the development of thrombosis and are associated with
CHD.25 26 39 Fibrinogen has been shown to be an
independent risk factor for CHD in women,39 whereas
elevated levels of plasma PAI-1 activity and TPA antigen have been
positively associated with myocardial reinfarction and CHD
mortality.25 40 41
In our study, we found no difference in plasma fibrinogen concentration between the physically active women and control subjects; however, the levels of plasma PAI-1 activity and TPA antigen were markedly lower in the active women. A recent study on a large cohort of postmenopausal women 60 to 69 years of age reported an inverse relation between physical activity, as assessed by self-administered questionnaire, and levels of plasma fibrinogen.42 However, this relation was significant only within the subgroup of obese women; for nonobese women, plasma fibrinogen concentrations did not differ between women who exercised 4 or more times per week and those who exercised 0 or 1 time per week,42 consistent with our results. Another recent study on men reported a significant decrease in plasma fibrinogen levels in older (60 to 82 years) but not in young (24 to 30 years) healthy men after 6 months of endurance exercise training.27 However, the pretraining levels of the older men were substantially higher than those of the control subjects in our study (3.6 versus 2.9 g/L). The young men, with markedly lower baseline levels of plasma fibrinogen, exhibited no change after the 6-month exercise program (2.3 to 2.2 g/L). Hence, the nonsignificant difference in the plasma fibrinogen levels in the physically active women versus control subjects in our study may be due to the low levels in the control subjects.
To the best of our knowledge, no other studies have examined the relation between regular physical activity and plasma concentrations of PAI-1 activity and TPA antigen in postmenopausal women.43 In their study on men, Stratton et al27 reported significant reductions in plasma levels of both PAI-1 activity and TPA antigen after 6 months of endurance training in the older (60 to 82 years) but not in the young (24 to 30 years) subjects. Our results are consistent with this finding, although the differences between plasma levels of PAI-1 activity in our physically active women versus control subjects were greater than those reported by Stratton et al in older men before versus after exercise training. Taken together, our findings and those of Stratton et al indicate that physically active middle-aged and older men and women demonstrate plasma concentrations of PAI-1 activity and TPA antigen that should be associated with a lower risk of CHD.
Plasma Insulin and Glucose
Elevated fasting levels of plasma insulin and impaired glucose
tolerance have been widely recognized as major independent risk factors
for the development of CHD.10 11 14 In addition, there is
evidence that individuals with normal glucose tolerance who have the
highest plasma glucose concentrations in response to a glucose
challenge are at an elevated risk of developing CHD.44
As emphasized recently by Haskell et al,43 no data exist on the relation between physical activity and fasting levels of glucose and insulin or glucose tolerance in postmenopausal women. Previous studies have examined these issues in older men or in mixed groups of men and women in which the results were not reported separately by sex.45 46 Our study is the first to report on healthy, nonobese postmenopausal women. Our data are consistent with the findings of previous studies on men and suggest that physically active postmenopausal women also demonstrate favorable fasting levels of glucose and insulin, as well as superior glucose tolerance and insulin responsiveness to an oral glucose challenge compared with less active control subjects. Although we did not measure insulin sensitivity directly, a strong correlation between fasting levels of plasma insulin and insulin sensitivity has recently been reported in nondiabetic humans.47 This finding, considered together with the markedly lower plasma insulin responses to the oral glucose tolerance test, suggests that the active women in our study were more insulin sensitive than the control subjects.
Body Composition
Body mass index, total body fat mass,48 and, more
recently, abdominal body fat accumulation12 13 49 have all
been associated with elevated risk of CHD. Of these factors, abdominal
fat accumulation is generally recognized as the strongest independent
risk factor for CHD.12 50 In our study we found
significantly lower body weight, body mass index, sum of skin folds,
estimated percent body fat, and waist circumference in the active women
compared with the control subjects (Table 3
). Waist-to-hip ratio did
not differ between the two groups.
Although previous studies on postmenopausal women have generally reported an association between high levels of physical activity and reduced body weight and total body fat,4 8 45 51 there are few data on the relation between physical activity and regional body fat distribution in this population. Waist-to-hip ratio, one of the commonly used measures of body fat distribution, has typically been shown to remain unchanged with physical activity.45 Recently, it has been shown that waist circumference is a better correlate of computed tomography–determined visceral adipose tissue level than waist-to-hip ratio and hence is a preferred index of cardiovascular risk.50 52 The lower waist circumference associated with high levels of physical activity in the present study is directionally consistent with the reduction observed after exercise training in older women by Kohrt and colleagues,45 although the magnitude of the physical activity–related difference was much greater in our cross-sectional comparison.
Androgenicity
SHBG is a circulating steroid-binding protein that binds
testosterone with high affinity and estrogen with lower affinity.
Hence, low SHBG levels are associated with a high ratio of free to
bound testosterone, suggesting elevated androgenicity. Previous
findings indicate that plasma SHBG levels are lower in postmenopausal
than in premenopausal women and that these lower levels are associated
with increased body mass index.28 The present study,
in which the physically active women exhibited significantly higher
levels of plasma SHBG than the control subjects, provides the only
available data on the association between physical activity and plasma
SHBG concentrations in women, either premenopausal or postmenopausal.
Our findings suggest that a physically active lifestyle is related to
lower androgenicity in this population. Because of its proposed link to
CHD risk as a key component of the insulin resistance
syndrome,14 24 this lower androgenicity is probably
associated with reduced coronary risk in women.
Plasma Lipids and Lipoprotein Levels
Plasma lipid and lipoprotein abnormalities have been identified as
major risk factors for the development of CHD.53 54 The
findings of our study suggest that in general, a physically active
lifestyle is associated with a more favorable lipid and lipoprotein
profile in healthy, nonobese postmenopausal women. In particular, our
physically active women demonstrated lower plasma TG and atherogenic
indexes, TC/HDL-C and TC/HDL2-C, as well as higher
plasma HDL2-C and HDL-C/LDL-C. In addition, the
active women tended to have lower levels of plasma TC and LDL-C and
higher levels of total plasma HDL-C than the control subjects. These
findings are generally consistent with those from previous studies in
postmenopausal women and, thus, confirm a reduced lipid-related CHD
risk in this population.5 6 7 8 55 56 57
Influence of Hormone Replacement Therapy on Risk Factors for
CHD
Because hormone replacement has been independently associated with
risk factors for CHD, it is possible that in our cross-sectional
comparison, some or all of the observed CHD risk factor differences
between the active women and control subjects were due to hormone
replacement rather than to the high level of chronic physical activity
per se. Our findings indicate that although hormone replacement may
have influenced the plasma levels of PAI-1 activity and TPA antigen in
this population of women, it was not a major determinant of the other
CHD risk factors. It should be emphasized, however, that the number of
women using hormone replacement in our study was small and, hence, some
relations may have gone undetected.
Influence of Body Composition, Dietary Intake, Aerobic Fitness, and
Level of Physical Activity on Risk Factors for CHD
One of the aims of this study was to determine the
contributions of both high levels of physical activity per se and the
associated low levels of total body and abdominal fat, a
high-carbohydrate/low-fat and low-protein diet, and high aerobic
fitness to hemostatic, metabolic, and androgenic CHD risk factors. The
results of the stepwise multiple regression analyses (Table 5)
indicate that waist circumference, rather than percent total body fat
or waist-to-hip ratio, was responsible for a significant portion of the
explained variability in the plasma levels of PAI-1 activity and TPA
antigen as well as lipid and lipoproteins of the healthy, nonobese
postmenopausal women in this study. This confirms previous findings
concerning the importance of abdominal adiposity rather than levels of
total body fat to risk factors for CHD.12 50 The finding
that waist circumference was a better predictor of these risk factors
than waist-to-hip ratio is not surprising in light of recent reports on
the preference of waist circumference over waist-to-hip ratio as a
measure of abdominal adiposity.50 52 Another finding from
the stepwise regression analysis is that aerobic fitness (as
assessed from O2max)
explained a significant portion of the explained variability in plasma
levels of HDL2-C. This is consistent with the
hypothesis that HDL2-C is the HDL-C subfraction most
modulated by physical activity.58 59 A third observation
was that the estimated physical activity levels of the subjects
accounted for the largest portion of the variability in the area under
the glucose curve during the oral glucose tolerance test. This link
between physical activity and glucose tolerance may be due in part to
the acute effects of muscle contraction (exercise) on peripheral
glucose uptake.60 Finally, the finding that body mass
index was responsible for most of the explained variability in plasma
SHBG levels is consistent with previous findings28 61 as
well as with the reported link between obesity and elevated
androgenicity.62
Clinical Significance
Recently a multiple risk factor syndrome, referred to variously as
syndrome X or the metabolic or insulin-resistance
syndrome,14 15 16 has been identified as an important
antecedent to CHD in middle-aged and older adults. This syndrome refers
to a clustering of CHD risk factors that is often observed in a single
individual, including hyperlipidemia, hyperinsulinemia, glucose
intolerance and insulin resistance, whole-body and abdominal obesity,
alterations in fibrinogen and modulators of fibrinolytic activity, and
elevated androgenicity (as reflected by decreased levels of SHBG in
women). Part of the marked increase in risk of CHD with advancing age
appears to be due to an increased prevalence of this clustering of risk
factors. Postmenopausal women, in particular, experience an accelerated
development of the syndrome and its individual components. Hence, it is
clinically important to examine lifestyle characteristics that may
exert a beneficial modulatory influence on a number of these risk
factors. In the present study, we show that a physically active
lifestyle is favorably associated with most of the factors of this
syndrome in a single population of healthy, nonobese postmenopausal
women. In addition, we show that in these women, body fat and its
distribution, dietary composition, and aerobic fitness are also
important correlates of the individual components of this syndrome.
Thus, our findings suggest that the lower risk of CHD observed in
physically active middle-aged and older women may be in part the result
of their superior levels of these hemostatic, metabolic, and androgenic
risk factors.
Limitations
The primary limitation of this cross-sectional study is that
genetic makeup may influence coronary risk factors independently of
physical activity or its correlates. Thus, the physically active women
may both be active and demonstrate a superior risk factor profile
because of a genetic predisposition. Second, the control group in our
study was exceptionally healthy. Although they were not exercising
regularly, most of them were at least minimally physically active.
Moreover, the control subjects were nonobese. Obesity per se is
associated with adverse levels of these risk factors and with the
insulin resistance syndrome.14 15 Because of this, our
control subjects may not have been representative of the more
sedentary overweight postmenopausal American woman. If so, differences
between physically active versus sedentary postmenopausal American
women were probably underestimated in our study.
Conclusions
We have shown that a physically active lifestyle is associated
with a favorable hemostatic, metabolic, and androgenic risk
factor profile for CHD in healthy, nonobese postmenopausal women.
In addition to high levels of physical activity, low levels of total
body and abdominal fat, a high-carbohydrate/low-fat and low-protein
diet, and high aerobic fitness also appear to contribute to the
activity-related differences in CHD risk factors in this
population.
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Acknowledgments |
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This investigation was supported by Public Health Services research grant 5-01-RR-00051 from the Division of Research Resources, Andrus Foundation grant AARPAF-OCG0937B, and National Institutes of Health (NIH) grants HL-39966 and AG-06537. Drs Stevenson and Davy were supported by individual National Research Service Awards HL-08870 and HL-08834, respectively, from the National Heart, Lung, and Blood Institute, NIH. Dr Seals was supported in part by National Institute on Aging Research Career Development Award AG-00423.
Received November 21, 1994; accepted February 21, 1995.
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