The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.

The independent and combined effects of exercise training and hormone replacement therapy (HRT) on body composition, fat distribution, glucose tolerance, and insulin action were studied in postmenopausal women, aged 68 +/- 5 yr, assigned to control (n = 19), exercise (n = 18), HRT (n = 15), and exercise + HRT (n = 16) groups. The exercise consisted of 2 mo of flexibility exercises followed by 9 mo of endurance exercise. HRT was conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Total and regional body composition were measured by dual-energy X-ray absorptiometry. Serum glucose and insulin responses were measured during a 2-h oral glucose tolerance test. There were significant main effects of exercise on reductions in total and regional (trunk, arms, legs) fat mass, increase in leg fat-free mass, and improvements in glucose tolerance and insulin action. There were significant main effects of HRT on the reduction of total fat mass (HRT, -3.0 +/- 4.0 kg; no HRT, -1.3 +/- 2.6 kg), with a strong trend for reductions in trunk and leg fat mass (both P = 0.07). There was also a significant improvement in insulin action in response to HRT. These results suggest that there are independent and additive effects of exercise training and HRT on the reduction in fat mass and improvement in insulin action in postmenopausal women; the effect of HRT on insulin action may be mediated, in part, through changes in central adiposity.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women. DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine. SUSBJECTS: A total of 323 healthy postmenopausal (66±5 y; mean±s.d.) women not using any hormone replacement. MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol. RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m2) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24–28 kg/m2). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size. CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.

Objective: To examine the effects of a 3-month low-intensity exercise program on physical frailty.Design: Randomized clinical trial.Setting: Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center.Participants: Eighty-four physically frail older adults (mean age, 83 +/- 4 yrs).Intervention: Three-month low-intensity supervised exercise (n = 48) versus unsupervised home-based flexibility activities (n = 36).Main Outcome Measures: Physical performance test, measures of balance, strength, flexibility, coordination, speed of reaction, peripheral sensation.Results: Significant improvement was made by the exercise group on our primary indicator of frailty, a physical performance test (PPT) (29 +/- 4 vs 31 +/- 4 out of a possible 36 points), as well as many of the risk factors previously identified as contributors to frailty; eg, reductions in flexibility, strength, gait speed, and poor balance. Although the home exercise control group showed increases in range of motion, the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT.Conclusions: Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults. They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty. Although results suggest that frailty is modifiable, it is not likely to be eliminated with exercise, and efforts should be directed toward preventing the condition.

To determine whether strength-trained individuals with physiological concentric left ventricular (LV) hypertrophy exhibit enhanced inotropic responses to catecholamines, we studied 11 bodybuilders, aged 33.0 +/- 2 (SE) yr old, and 10 sedentary healthy subjects, aged 31.3 +/- 2.4 yr old, at baseline and during infusion of incremental doses of dobutamine after atropine. The bodybuilders had larger LV mass, posterior wall and septal wall thicknesses, and wall thickness-to-radius ratio, assessed with two-dimensional echocardiography, than did the sedentary subjects. There was a significant correlation between LV mass and lean body mass irrespective of training status. Baseline LV fractional shortening was similar in the two groups. There was a greater inotropic response to dobutamine in the strength-trained individuals, as evidenced by a steeper slope of the fractional shortening-end-systolic wall stress relationship with a higher y-axis intercept and by a shallower end-systolic wall stress-end systolic diameter relationship without changes in end-diastolic diameter. The heart rate response to dobutamine was attenuated in the strength-trained athletes. There was a significant correlation (r = 0.604, P < 0.05) between the inotropic sensitivity to dobutamine and LV mass normalized for lean body mass in the bodybuilders. The data suggest that concentric LV physiological hypertrophy in the resistance-trained individuals is associated with enhanced inotropic but not chronotropic responses to catecholamines.

BACKGROUND:It is not known whether exercise training can induce a reduction of blood pressure (BP) and a regression of left ventricular hypertrophy (LVH) in older hypertensive subjects. This study was designed to determine whether endurance exercise training, by lowering BP, can induce regression of LVH and left ventricular (LV) concentric remodeling in older hypertensive adults.METHODS:We studied 11 older adults with mild to moderate hypertension (BP 152.0 +/- 2.5/91.3 +/- 1.5 mm Hg, mean +/- SE), 65.5 +/- 1.2 years old, who exercised for 6.8 +/- 3.8 months. Seven sedentary hypertensive (BP 153 +/- 3/89 +/- 2 mm Hg) subjects, 68.5 +/- 1 years old, served as controls. LV size and geometry and function were assessed with the use of two-dimensional echocardiography.RESULTS:Exercise training increased aerobic power by 16% (p < .001), and it decreased systolic (p < .05) and diastolic (p < .05) BP, LV wall thickness (from 12.8 +/- 0.4 mm to 11.3 +/- 0.3 mm; p < .05), and the wall thickness-to-radius (h/r) ratio (from 0.48 +/- 0.02 to 0.41 +/- 0.01; p < .05). There were no significant changes in the controls. The changes in LV mass index (deltaLVMI) were different between the two groups. LV mass index decreased in the exercise group (deltaLVMI - 14.3 +/- 3.3 g) but not in the controls (deltaLVMI 1.4 +/- 4.1 g; p = .009). A multiple stepwise regression analysis showed that among clinical and physiological variables including changes in resting systolic BP, aerobic power, body mass index, and systolic BP during submaximal and maximal exercise, only the reduction in resting systolic BP correlated significantly with a regression of concentric remodeling (delta h/r ratio r = .80; p = .003). The other variables did not add to the ability of the model to predict changes in the h/r ratio.CONCLUSIONS:The data suggest that exercise training can reduce BP and induce partial regression of LVH and LV concentric remodeling in older adults with mild or moderate hypertension.

We studied the effects of age and gender on cardiovascular responses to beta-adrenergic stimulation with the use of two-dimensional echocardiography in 16 young (aged 20-31) and 20 older (aged 60-75) healthy individuals. Following administration of atropine, each subject was given an infusion of isoproterenol at incremental doses from 0.010 to 0.030 microgram kg-1 min-1. The slopes of the fractional shortening-end-systolic wall stress (FS-sigma es) relationships were steeper in the young men (-0.87 +/- 0.28, n = 8) compared to the older men (-0.41 +/- 0.13, n = 10), and in the young women (-0.55 +/- 0.14, n = 8) compared to the older women (-0.38 +/- 0.13, n = 10). Furthermore, the magnitude of the age-associated differences in these slopes was larger in the men (old vs young) than in the women (old vs young) which, in the absence of changes in preload, suggests a greater decline in the contractile response to isoproterenol with advancing age in men compared to women. Furthermore, the men exhibited a greater attenuation of chronotropic response to isoproterenol than did the women. These observations suggest that gender plays a significant role in the age-associated decline in inotropic and chronotropic responses to beta-adrenergic stimulation, with men exhibiting a greater decline with aging than women.

BACKGROUND:The age-associated impairment in left ventricular (LV) systolic function appears to be mostly detectable during exercise or sympathetic stimulation. We hypothesized that the decline in cardiac function could be unmasked by an acute increase in afterload induced by phenylephrine. We further sought to examine whether the deterioration in cardiac function is influenced by gender.METHODS:We studied 17 young (20-31 years old) and 21 older healthy subjects (60-75 years old) who were given infusions of incremental doses of phenylephrine following cardiac muscarinic receptor blockade with atropine. Left ventricular systolic function was assessed with 2-D echocardiography.RESULTS:The young subjects exhibited a paradoxical increase in heart rate in response to alpha-adrenergic stimulation, but the older subjects did not (p < .01). The increase in systolic blood pressure in response to phenylephrine was influenced by age and gender (i.e., greater in the younger men and older women), whereas the increase in diastolic blood pressure was greater in the younger than the older subjects of both sexes. The changes in LV end-diastolic diameter with phenylephrine were unaffected by age or gender. The slope of the systolic shortening-end systolic wall stress relationship was significantly steeper in the older subjects, suggesting a decline in the contractile response to an acute increase in afterload with aging.CONCLUSIONS:This study's findings suggest that age can significantly influence the cardiovascular responses to alpha-adrenergic stimulation and that phenylephrine, by acutely increasing afterload, is effective in unmasking the age-associated deterioration in left ventricular systolic function. Further, it appears that the increase in systolic blood pressure in response to an alpha-adrenergic challenge is significantly influenced not only by age but also by gender.

1935 The independent and combined effects of exercise training and hormone replacement therapy (HRT) on glucose (GLU) tolerance and insulin (INS) action were studied in postmenopausal women, aged 68±5 yr, assigned to control (Con; n=18), exercise (Ex; n=18), HRT (n=16), and Ex+HRT (n=16) groups. The exercise consisted of 2 mo of flexibility training followed by 9 mo of endurance exercise. Body composition was estimated by DXA. Serum GLU and INS responses were measured during a 2 hr OGTT. Changes (±SD) were: (Table)TableThese data suggest that HRT improves INS action and potentiates the enhancement in INS action that occurs in response to exercise training, possibly due to an augmentation of fat loss.

1943 The effects of aging on the cardiovascular system have been well characterized in men. However, data on the effects of aging on the oxygen transport capacity of the cardiovascular system are lacking in women. Therefore, the present study was designed to characterize the effects of age on maximal O2 uptake (VO2max), cardiac output (Q max) and the arterio-venous O2 content difference (a-v O2 diff) in women 60 to 90 yrs of age. Fifty two elderly women (eld) 83 ± 4.4 (mean ± SD) yrs of age and 42 women 64 ± 4 yrs (YO) of age participated in this study. VO2 max was measured during treadmill exercise. Q max was assessed during treadmill exercise with the use of the acetylene rebreathing procedure. VO2 max was 35% lower in the elderly women (0.89 ± 0.20 L/min vs 1.36 0.0.20 L/min; p<0.01) compared to the YO group of women. The lower VO2 max was mediated predominately by a decrease in Qmax, 8.6 ± 1.90 L/min in the elderly group vs 11.4 ± 1.65 L/min in the YO group (p<0.01). A 20% decline in peak heart rate 127 ± 18 bpm in the eld group vs 159 ± 13 in the YO group (p<0.01) accounted for most of the decline in Q group. The a-v O2 diff decreased 12% in the elderly group compared to YO group (12.0 ± 1.7 mL O2/100 mL of blood vs 10.6 ± 2.2 mL O2/100 mL of blood; p<0.05). The results suggest that the decline in VO2 max in women between the ages of 60-90 is due predominately to a decrease in Q max and to a lesser extent in the a-v O2 diff. Supported by NIH grants AG-13629, AG-12235 and AG-05562

BACKGROUND The purpose of this study was to determine the relationship between peak aerobic power (VO2peak) and performance on a modified Physical Performance Test (modified PPT) in older women. METHODS One hundred one women aged 75 years and older seeking enrollment in randomized, controlled trials of exercise and/or hormone replacement therapy were recruited from the community-at-large and from congregate living sites. Measures obtained included VO2peak, a modified PPT, and self-reports about performance of activities of daily living. RESULTS Simple regression analysis demonstrated that VO2peak was associated with total PPT score (r =.53, p <.001), gait speed (r =.44, p <.001), time to arise from a chair five times (r =.43, p = <.001), and time to climb one flight of stairs (r =.36, p =.007). Multiple regression analysis revealed that the relationships between VO2peak and total modified PPT score, gait speed, chair rise time, and time to climb one flight of stairs were independent of age. CONCLUSIONS Peak aerobic power is a significant independent predictor of performance on a standardized test of physical function in older women and is an important component of physical frailty in this population.