As an ancillary report to a large National Institutes of Health (NIH)–funded trial, we examined the effects of 6 months of exercise training at 50%, 100%, and 150% of the NIH Consensus Recommendations for physical activity (i.e., 4, 8, and 12 kcal/kg of energy expenditure/wk [KKW]) versus a nonexercise control group on the metabolic syndrome (MS) in sedentary, overweight, moderately hypertensive, postmenopausal women. We examined the clinically defined National Cholesterol Education Program MS, individual components scores, and summed z-scores, expressed as a continuous variable (zMS), using chi-square and general linear models to assess the clinical and progressive nature of MS, respectively. Our results showed significant improvements in zMS for all exercise groups and MS for the 8- and 12 KKW groups only (all, p for trend = 0.02). Post hoc analyses showed that 12 KKW for zMS and 8 and 12 KKW for MS was significant versus the control group (all, p <0.05). When examining the composite scores, we observed significant trends for improvement in waist circumference (p for trend = 0.001), fasting glucose (p for trend = 0.01), and systolic blood pressure (p for trend = 0.02), which appeared to be dose dependent, given the additive nature for incorporating the within-group improvements in waist circumference (4, 8, and 12 KKW), fasting glucose (8 and 12 KKW), and systolic blood pressure (12 KKW). Our results suggest that low-to-moderate intensity cardiorespiratory exercise appears to improve components of the MS in postmenopausal women at levels at or greater than NIH recommendations and that zMS improves at half the NIH recommendations. Greater levels of energy expenditure appear to enhance this effect by incorporating a greater number of requisite MS composite scores.
The metabolic syndrome (MS) is a combination of risk factors composed of abdominal obesity, insulin resistance, hypertension, and lipid abnormalities and represents the erosion of the individual component parts associated with its diagnosis. We hypothesized that given the categorical nature of the MS, a full appreciation for improvement might not be adequately portrayed by simply measuring the MS cutpoints. We have recently published results from this hypothesis in a cross-sectional analysis from the Aerobics Center Longitudinal Study. We based this hypothesis on the observation that MS is constructed by the presence or absence of a component score composed of defined cutpoints. It is also unclear which components drive the MS or, when applicable, reduce its prevalence after exercise training. Thus, the categorical nature of the MS assessment might not fully explain the benefits of an exercise intervention, given the nature of the assessment as a failure to meet a particular component’s cutpoint, despite marked improvement, would still qualify a patient for the MS. In a recent randomized controlled trial, we demonstrated that cardiorespiratory exercise administered at 50%, 100%, and 150% of the National Institutes of Health (NIH) Consensus Panel physical activity recommendation increases maximum cardiorespiratory fitness in a dose-wise fashion. We present here an analysis of the effects of moderate intensity exercise training on the MS in sedentary, overweight or obese, postmenopausal women with elevated blood pressure considered to have an elevated risk of cardiovascular disease.
Methods
The complete design, methods, and primary outcomes of the Dose-Response to Exercise in Women Aged 45 to 75 Years (DREW) study have been previously published. In brief, the DREW study was a randomized, dose–response exercise training trial complying with the Declaration of Helsinki and comparing a nonexercise control group and 3 groups exercising at incremental doses (50%, 100%, and 150%) of the minimal NIH Consensus Development Panel’s recommendation for energy expenditure. The Cooper Institute and Pennington Biomedical Research Center’s institutional review boards initially and subsequently reviewed our protocol annually. The primary outcomes for the DREW study included maximum cardiorespiratory capacity, which was calculated as the average of 2 baseline and 2 follow-up exercise tests and the blood pressure at rest. The clinicaltrials.gov identifier is NCT00011193 .
After an initial evaluation and run-in period, we randomized 464 postmenopausal women (age 45 to 75 years) to 1 of 3 exercise training groups or a nonexercise control group for a 6-month intervention period. The exercise intensity for the present study was fixed at 50% of the measured maximum cardiorespiratory capacity. During the exercise portion of the study, there were distinct and separate intervention and assessment teams, and all assessment staff were kept unaware of the participant randomization assignment. The study participants were sedentary (exercising <20 minutes; <3 days/wk; <8,000 steps/day assessed during a 1-week period), overweight or obese (body mass index 25.0 to 43.0 kg/m 2 ), and had a systolic blood pressure of 120 to 160 mm Hg. We excluded women who had a history of stroke, myocardial infarction, or any serious medical condition that prevented participants from adhering to the protocol or exercising safely. Our present analysis was limited to 408 women with complete data for MS risk factors at baseline and follow-up.
In an attempt to elucidate the progression or improvements surrounding the MS, we approached our analysis by examining categorically defined MS and MS according to the z-scores (zMS) from the National Cholesterol and Education Program components described in the Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity for subjects from the United States. We calculated the presence of MS by taking each participant’s individual score at baseline and follow-up and subtracting it from the cohort’s baseline mean value. The resultant value of each was then divided by the cohort’s SD for that score, summed, and then divided by the number of the composite scores. This approach has been used previously in several other studies.
We used chi-square and generalized linear models to analyze the influences of the differing doses of exercise training on the MS and zMS. When significant trends were observed, we explored our findings further for pairwise comparisons between the exercise training groups and the control group using a Dunnett-Hsu post hoc assessment. The Dunnett-Hsu test allows specific multiple pairwise comparisons while still protecting against type I statistical errors. We covaried all our analyses with the participant’s age, baseline MS scores for each composite viable, as appropriate, and hypertension medication (28% of cohort), hyperlipidemia medication (16% of cohort), hormonal therapy (15% of cohort), thyroid medication (15% of cohort), antidepressants (18% of cohort), and glucose control medication (1% of cohort). Within-group differences between baseline and the follow-up duration are reported as the mean and 95% confidence intervals (CIs). All reported p values are 2 sided (p <0.05), and our analyses were performed using the Statistical Package for Social Sciences, version 19.0 (IBM, Somers, New York).
Results
The present report details the effects of 6 months of exercise training on the MS in 408 participants. The cohort’s demographic, anthropometric, blood pressure, and cardiorespiratory capacity data are listed in Table 1 . The hematologic and MS score characteristics are listed in Table 2 . Medication use is listed in Table 3 . Overall, the participants in the present analysis were 45 to 75 years old, weighed 58.2 to 112.8 kg, and had a body mass index of 23.2 to 40.9 kg/m 2 . Similar to our primary outcome study, we observed a significant, dose-dependent increase in maximum cardiorespiratory capacity (p for trend = 0.0001) for the 4 KKW (0.64 ml/kg/min, 95% CI 0.38 to 0.95), 8 KKW (1.28 ml/kg/min, 95% CI 0.91 to 1.65), 12 KKW (1.67 ml/kg/min, 95% CI 1.32 to 2.03) groups, with each group having statistically significant differences (p <0.001) versus the control group (−0.18 ml/kg/min, 95% CI −0.54 to 0.18). Although we did not observe a significant difference between baseline and follow-up regarding medication use, a significant percentage of our cohort presented to the study with MS (78%).
| Variable | All | Exercise Treatment Group | |||
|---|---|---|---|---|---|
| Control | 4 KKW | 8 KKW | 12 KKW | ||
| Age (yrs) | 57.23 ± 6.4 | 57.12 ± 5.8 | 57.94 ± 6.6 | 56.91 ± 6.6 | 56.57 ± 6.5 |
| Height (cm) | |||||
| Baseline | 162.89 ± 5.7 | 162.87 ± 6.2 | 162.77 ± 5.8 | 162.40 ± 5.3 | 163.53 ± 5.5 |
| Follow-up | 162.98 ± 5.7 | 162.99 ± 6.2 | 162.81 ± 5.8 | 162.56 ± 5.3 | 163.59 ± 5.5 |
| Weight (kg) | |||||
| Baseline | 84.28 ± 11.9 | 85.52 ± 12.5 | 83.73 ± 11.4 | 85.03 ± 12.4 | 83.23 ± 11.4 |
| Follow-up | 82.83 ± 11.9 | 84.12 ± 12.5 | 82.42 ± 11.4 | 83.14 ± 12.4 | 81.91 ± 11.6 |
| BMI (kg/m 2 ) | |||||
| Baseline | 31.72 ± 3.8 | 32.18 ± 4.0 | 31.57 ± 3.7 | 32.19 ± 4.0 | 31.07 ± 3.6 |
| Follow-up | 31.15 ± 3.8 | 31.65 ± 4.0 | 31.06 ± 3.7 | 31.42 ± 4.1 | 30.54 ± 3.6 |
| Waist circumference (cm) ∗ | |||||
| Baseline | 100.85 ± 11.6 | 102.28 ± 11.9 | 100.27 ± 11.2 | 101.87 ± 11.4 | 99.42 ± 12.0 |
| Follow-up | 98.76 ± 11.4 | 102.42 ± 12.3 | 97.48 ± 10.0 | 99.10 ± 12.0 | 96.84 ± 11.2 |
| Hip circumference (cm) | |||||
| Baseline | 114.88 ± 9.0 | 116.02 ± 9.5 | 114.43 ± 8.5 | 115.25 ± 9.2 | 114.12 ± 9.2 |
| Follow-up | 112.82 ± 9.6 | 114.29 ± 9.5 | 112.49 ± 9.1 | 113.18 ± 10.8 | 111.57 ± 9.4 |
| Systolic blood pressure (mm Hg) ∗ | |||||
| Baseline | 139.55 ± 13.1 | 141.68 ± 12.4 | 138.65 ± 13.3 | 139.90 ± 13.8 | 138.53 ± 12.8 |
| Follow-up | 138.06 ± 13.5 | 138.78 ± 11.7 | 139.78 ± 13.5 | 137.38 ± 13.9 | 135.38 ± 14.3 |
| Diastolic blood pressure (mm Hg) ∗ | |||||
| Baseline | 80.69 ± 8.4 | 80.64 ± 7.9 | 80.43 ± 8.7 | 80.81 ± 8.3 | 81.03 ± 8.7 |
| Follow-up | 80.82 ± 8.2 | 80.18 ± 7.6 | 81.40 ± 8.0 | 80.58 ± 9.4 | 80.78 ± 8.2 |
| Relative VO 2max (ml/kg/min) | |||||
| Baseline | 15.50 ± 2.9 | 15.64 ± 2.9 | 15.43 ± 3.0 | 14.98 ± 2.4 | 15.93 ± 3.0 |
| Follow-up | 16.33 ± 3.0 | 15.43 ± 2.9 | 16.08 ± 3.1 | 16.38 ± 2.6 | 17.54 ± 3.0 |
| Absolute VO 2max (L/min) | |||||
| Baseline | 1.30 ± 0.3 | 1.33 ± 0.3 | 1.28 ± 0.3 | 1.27 ± 0.2 | 1.31 ± 0.2 |
| Follow-up | 1.34 ± 0.3 | 1.29 ± 0.3 | 1.31 ± 0.2 | 1.35 ± 0.3 | 1.43 ± 0.3 |
| Maximum heart rate (beats/min) | |||||
| Baseline | 151.56 ± 16.4 | 151.69 ± 15.7 | 150.50 ± 17.3 | 151.59 ± 15.7 | 153.01 ± 16.6 |
| Follow-up | 150.53 ± 16.4 | 147.88 ± 16.5 | 149.74 ± 16.0 | 152.23 ± 16.0 | 152.72 ± 17.0 |
∗ Component of NCEP Adult Treatment Panel III metabolic syndrome.
| All | Exercise Treatment Group | ||||
|---|---|---|---|---|---|
| Control | 4 KKW | 8 KKW | 12 KKW | ||
| Blood parameters † | |||||
| Cholesterol (mg/dl) | |||||
| Baseline | 201.54 ± 29.9 | 201.33 ± 29.7 | 200.60 ± 31.6 | 202.11 ± 29.0 | 202.66 ± 28.6 |
| Follow-up | 203.03 ± 31.7 | 205.19 ± 35.4 | 202.18 ± 31.8 | 201.94 ± 27.9 | 203.23 ± 31.4 |
| HDL (mg/dl) ∗ | |||||
| Baseline | 57.47 ± 14.4 | 57.02 ± 14.2 | 57.67 ± 14.3 | 57.28 ± 15.7 | 57.78 ± 13.5 |
| Follow-up | 57.01 ± 13.3 | 56.78 ± 12.2 | 57.42 ± 13.3 | 57.35 ± 15.1 | 56.32 ± 12.8 |
| LDL (mg/dl) | |||||
| Baseline | 118.19 ± 26.7 | 117.92 ± 26.2 | 116.99 ± 27.6 | 118.46 ± 25.4 | 120.03 ± 27.3 |
| Follow-up | 120.74 ± 29.0 | 122.55 ± 33.3 | 120.34 ± 28.2 | 119.21 ± 26.7 | 121.00 ± 28.4 |
| VLDL (mg/dl) | |||||
| Baseline | 26.09 ± 12.6 | 27.36 ± 14.0 | 25.94 ± 11.9 | 26.36 ± 12.1 | 24.85 ± 12.8 |
| Follow-up | 25.00 ± 12.2 | 25.70 ± 11.0 | 24.42 ± 12.1 | 25.38 ± 13.1 | 24.85 ± 12.8 |
| Cholesterol/HDL ratio | |||||
| Baseline | 3.69 ± 1.0 | 3.71 ± 0.9 | 3.66 ± 1.0 | 3.74 ± 1.0 | 3.68 ± 0.9 |
| Follow-up | 3.73 ± 1.0 | 3.78 ± 1.0 | 3.68 ± 1.0 | 3.73 ± 1.0 | 3.76 ± 0.9 |
| Triglycerides (mg/dl) ∗ | |||||
| Baseline | 131.20 ± 64.9 | 136.58 ± 70.0 | 129.44 ± 59.3 | 131.89 ± 60.2 | 128.01 ± 72.3 |
| Follow-up | 129.39 ± 85.9 | 141.24 ± 132.2 | 122.19 ± 60.6 | 126.95 ± 65.7 | 131.00 ± 77.5 |
| Glucose (mg/dl) ∗ | |||||
| Baseline | 94.61 ± 9.9 | 95.20 ± 13.3 | 94.08 ± 8.7 | 94.40 ± 9.1 | 95.02 ± 8.5 |
| Follow-up | 93.89 ± 9.1 | 96.44 ± 10.2 | 93.22 ± 9.0 | 92.99 ± 8.8 | 93.25 ± 8.2 |
| Insulin (pmol/L) | |||||
| Baseline | 140.18 ± 410.9 | 121.95 ± 384.9 | 163.67 ± 443.7 | 128.42 ± 395.2 | 133.21 ± 403.0 |
| Follow-up | 143.39 ± 416.0 | 137.83 ± 409.0 | 163.48 ± 443.7 | 127.55 ± 395.4 | 132.99 ± 403.1 |
| Metabolic Syndrome | |||||
| Score | |||||
| Baseline | 3.20 ± 0.9 | 3.30 ± 1.0 | 3.19 ± 0.9 | 3.15 ± 0.9 | 3.16 ± 0.9 |
| Follow-up | 3.05 ± 0.9 | 3.24 ± 0.9 | 3.10 ± 0.9 | 2.94 ± 0.9 | 2.87 ± 1.0 |
| Prevalence | |||||
| Baseline | 319, 78% | 69, 77% | 113, 81% | 65, 77% | 72, 77.4% |
| Follow-up | 299, 73% | 72, 80% | 110, 79% | 59, 69% | 58, 62.4% |
∗ Component of National Cholesterol Education Program Adult Treatment Panel III MS.
† SI conversions: to convert total, low-density lipoprotein, and high-density lipoprotein cholesterol to mmol/L, multiply by 0.0259; triglycerides to mmol/L, multiply by 0.0113; glucose to mmol/L, multiply by 0.0555; and insulin to pmol/L multiply by 6.945.
| Medication | All (n) | Exercise Treatment Group (n) | |||
|---|---|---|---|---|---|
| Control | 4 KKW | 8 KKW | 12 KKW | ||
| Blood pressure | |||||
| Baseline | 113 (28) | 22 (24) | 37 (26) | 26 (31) | 28 (30) |
| Follow-up | 108 (28) | 20 (24) | 37 (29) | 29 (36) | 22 (25) |
| Antidepressant | |||||
| Baseline | 75 (18) | 14 (16) | 26 (19) | 16 (19) | 19 (20) |
| Follow-up | 71 (19) | 16 (19) | 24 (19) | 14 (17) | 17 (20) |
| Cholesterol | |||||
| Baseline | 64 (16) | 14 (16) | 27 (19) | 13 (15) | 10 (11) |
| Follow-up | 57 (15) | 14 (17) | 22 (17) | 13 (16) | 8 (9) |
| Glucose regulation | |||||
| Baseline | 2 (1) | 1 (1) | 0 (0) | 0 (0) | 1 (1) |
| Follow-up | 4 (1) | 1 (1) | 1 (1) | 1 (1) | 1 (1) |
| Thyroid | |||||
| Baseline | 62 (15) | 14 (16) | 17 (12) | 14 (17) | 17 (18) |
| Follow-up | 53 (14) | 12 (14) | 14 (11) | 13 (16) | 14 (16) |
| Current hormonal therapy | |||||
| Baseline | 183 (45) | 47 (52) | 58 (41) | 35 (41) | 43 (46) |
| Follow-up | 152 (37) | 38 (42) | 47 (34) | 31 (37) | 36 (39) |
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