Lyndon J. Joseph

Effects of exercise rehabilitation on endothelial reactivity in older patients with peripheral arterial disease

Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Endothelial function, which is a measure of vascular health, is impaired in patients with PAD. We examined the effects of 6 months of aerobic exercise rehabilitation on brachial artery endothelial function, assessed using high-frequency ultrasonography, and calf blood flow in 19 older PAD patients (age 69 +/- 1 years, mean +/- SEM) with intermittent claudication (ankle to brachial artery index of 0.73 +/- 0.04). After exercise, the time to onset of claudication pain increased by 94%, from 271 +/- 49 to 525 +/- 80 seconds (p <0.01), and the time to maximal claudication pain increased by 43%, from 623 +/- 77 to 889 +/- 75 seconds (p <0.05). Exercise rehabilitation increased the flow-mediated brachial arterial diameter by 61%, from 0.18 +/- 0.03 to 0.29 +/- 0.04 mm (p <0.005), as well as the relative change in brachial arterial diameter from the resting state by 60%, from 4.81 +/- 0.82% to 7.97 +/- 1.03% (p <0.005). Maximal calf blood flow (14.2 +/- 1.0 vs 19.2 +/- 2.0 ml/100 ml/min; p = 0.04), and postocclusive reactive hyperemic blood flow (9.8 +/- 0.8 vs 11.3 +/- 0.7 ml/100 ml/min; p = 0.1) increased 35% and 15%, respectively. In conclusion, exercise rehabilitation improved ambulatory function, endothelial-dependent dilation, and calf blood flow in older PAD patients with intermittent claudication.

Reduced Skeletal Muscle Capillarization and Glucose Intolerance

Objective: Reduced capillarization in hemiparetic skeletal muscle of chronic stroke patients can limit insulin, glucose, and oxygen supply to muscle, thereby contributing to impaired glucose metabolism and cardiovascular deconditioning. We hypothesized that compared to sedentary controls, stroke subjects have reduced skeletal muscle capillarization that is associated with glucose intolerance and reduced peak oxygen consumption (Vo2peak). Methods: Twelve chronic stroke subjects (ages, 62.1±2.8 years), and matched sedentary controls with impaired (n=12) or normal (n=12) glucose tolerance underwent oral glucose tolerance tests, exercise tests, and vastus lateralis biopsies. Results: Stroke subjects had lower capillarization in hemiparetic muscle than in nonparetic muscle and normal glucose tolerant controls (∼22 and ∼28%, respectively; P<0.05) and had similar bilateral capillarization, compared to controls with impaired glucose tolerance. Capillary density in hemiparetic muscle inversely correlated with 120‐minute glucose (r=−0.70, P<0.01) and glucose area under the curve (r=−0.78, P<0.01). Vo2peak was ∼40% lower in stroke subjects, compared to controls (P<0.001), but did not correlate with capillarization (P=n.s.). Conclusions: Hemiparetic muscle capillarization is reduced after stroke, and reduced capillarization is associated with glucose intolerance in stroke and control subjects. Interventions to increase skeletal muscle capillarization may prove beneficial for improving glucose metabolism in chronic stroke patients.

Weight Loss and Low-Intensity Exercise for the Treatment of Metabolic Syndrome in Obese Postmenopausal Women

BACKGROUND The prevalence of the metabolic syndrome (MetSyn) approaches 50% in postmenopausal women. This study examines the efficacy of lifestyle modification for the treatment of MetSyn and its associated risk for cardiovascular disease and diabetes in this population. METHODS This prospective controlled study examines the effects of a 6-month weight loss and low-intensity exercise program (WL+LEX) on body composition (dual-energy X-ray absorptiometry and abdominal computed tomography scans), fasting glucose and lipid levels, cytokines, and blood pressure in postmenopausal women with and without MetSyn. RESULTS WL+LEX reduced body weight (MetSyn: -5% vs non-MetSyn: -7%) and fat mass (-11% vs -15%) and increased VO(2max) (+2% vs +3%) in both MetSyn (N = 35) and non-MetSyn (N = 41) groups. Constituents of MetSyn decreased comparably in both groups. Fifteen (45%) MetSyn participants responded (R) by converting to non-MetSyn, 18 remained MetSyn (NR), and 2 had missing data. Reduction in fat mass (-15% vs -8%, p = .02) was greater in R than NR, but there were no between-group differences in changes in VO(2max), cytokines, or other variables. The decrease in the number of MetSyn criteria was greater in R than in NR (-27 vs -13, p < .0001) due to decreases in blood pressure (p < .01), glucose (p = .02), and with a trend for triglyceride (p = .07). Reductions in fat mass best predicted resolution of MetSyn (p = .04). CONCLUSIONS Women who lose more fat are more likely to lower blood pressure, glucose, and triglyceride levels to resolve MetSyn. Thus, a WL+LEX program effectively treats postmenopausal women with MetSyn.

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men

Objective: Recent studies indicate that abdominal fat accumulation, in particular intra-abdominal fat, is related to impaired endothelial function in young healthy volunteers. The aim of this study was to examine whether the distribution of body fat depots is related to impaired endothelial function in older men.Methods: Cross-sectional sample of 38 older (68±1 y) sedentary (VO2max=2.4±0.1 l/min) men. Flow-mediated endothelial dependent vasodilation (EDD) was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Abdominal subcutaneous and visceral fat depots were assessed by computed tomography scan (CT-scan) at the L4–L5 region in the supine position. Percentage body fat was assessed via dual-energy X-ray absorptiometry (DEXA).Results: Flow-mediated percentage change in brachial artery was 7.6±0.7%, suggesting an impaired flow-mediated EDD. Using simple linear regression analysis, there were no statistically significant relationship observed between flow-mediated EDD and the indices of total and abdominal adiposity (percentage body fat=29.3±0.9%, r=−0.11; total abdominal fat area=465±23 cm2, r=−0.1; intra-abdominal fat area=200±14 cm2, r=−0.14; subcutaneous fat area=265±13 cm2, r=−0.05; BMI=29.3±0.9 kg/m2, r=−0.07; and waist to hip ratio=0.98±0.01, r=−0.20).Conclusion: These findings suggest that in older sedentary men there is no clear correlation between adiposity and body fat distribution and impairment of flow-mediated endothelium dependent vasodilation.

Plasma Adiponectin Levels are Associated with Insulin Sensitivity in Stroke Survivors

OBJECTIVE Adiponectin is an anti-inflammatory and insulin-sensitizing adipokine produced by adipose tissue. The purpose of this study was to determine the relationships between adiponectin and glucose metabolism in stroke survivors and to compare adiponectin levels between patients with stroke and nonstroke control subjects similar in age, sex, and body mass index. METHODS In all, 52 stroke survivors (35 men, 17 women) and 33 nonstroke control subjects (22 men, 11 women) had plasma adiponectin levels measured by RIA, an oral glucose tolerance test, and a peak oxygen consumption-graded treadmill test. Insulin resistance (IR) and insulin sensitivity were assessed using the homeostasis model assessment for IR (HOMA-IR) and insulin sensitivity index (ISI(M)). RESULTS Adiponectin levels were positively associated with age (r = 0.32, P < .05) and negatively associated with glucose homeostasis (fasting glucose: r = -0.42; insulin: r = -0.36; Glucose at (120 min): r = -0.39; HOMA-IR: r = -0.45; and ISI(M): r = 0.44, all P < .01) in stroke survivors. Adiponectin levels were significantly different among normal glucose-tolerant, impaired glucose-tolerant, and diabetic patients with stroke (11.1 +/- 0.99 v 9.56 +/- 0.99 v 5.75 +/- 1.55 ng/mL, P < .05). Adiponectin levels were 62% higher in patients with stroke than control subjects (9.29 +/- 0.62 v 5.80 +/- 0.40 ng/mL, P < .001) despite greater fasting insulin levels (81%) and 120-minute insulin (70%) in stroke survivors than control subjects (P < .05). HOMA-IR was 78% higher and ISI(M) was 81% lower in stroke survivors than control subjects (P < .05). CONCLUSIONS Plasma adiponectin levels are associated with age and insulin sensitivity but not adiposity in stroke survivors. The paradoxical finding that the more IR stroke survivors had higher adiponectin levels than more insulin-sensitive control subjects suggests that perhaps anti-inflammatory cytokines increase to counter an inflamed and IR state in stroke survivors.

Aging and Marathon Times in an 81-Year-Old Man Who Competed in 591 Marathons

I t has been hypothesized that the age-associated decline in maximal aerobic capacity (VO2max) is attenuated in healthy endurancetrained athletes who continue to engage in habitual exercise compared with sedentary persons.1–6 However, data are disparate because some studies find no significant difference between the absolute decline in VO2max with age in athletes and their sedentary peers,7,8 or they find even greater absolute decreases in VO2max with age in athletes than in sedentary people.9,10 Therefore, this hypothesis remains controversial. In this case report we chronicle 3 decades of marathon training, racing, and aerobic capacity testing over a 12-year period in an 81-year-old man who has run 591 marathons. This study was approved by the University of Maryland Institutional Review Board and the subject signed informed consent for participation in this study. • • • An 81-year old white man began running marathons at the age of 49. As of December 1, 2001, he had competed in 591 marathons. Over the course of his running career, he kept detailed training logs reflecting total mileage, number of races, yearly best race times, and yearly race time averages. As part of a larger study in master athletes,7,9,11 starting at age 68 years, this man also made 6 visits to our facility over a 12-year period for measurement of VO2max. Eligibility criteria for entry into the master athlete study, as previously described,7 included: (1) exercised vigorously 4 times/week, with a VO2max 2.5 SDs above the ageadjusted norm1; (2) nonobese (body mass index 26 kg · m); and (3) no history of coronary artery disease, diabetes mellitus, hyperlipidemia, or hypertension. VO2max was determined using a modified Balke protocol as previously described.9 Initially, the treadmill speed was set to produce approximately 70% of the subject’s predicted maximal heart rate. The elevation of the treadmill was increased from 0% to 4% after 2 minutes, to 6% after 4 minutes, and then increased by 2% every minute until the subject reached voluntary exhaustion, and could not continue to exercise. For the first test, ventilation was collected through a low-resistance, low-dead space, 3-way mixing valve (Otis McKerrow, Bayview Medical, Baltimore, Maryland) into a mixing chamber and a 120-L Tissot spirometer. The expired gas concentrations were measured every 30 seconds using Beckman carbon dioxide and oxygen analyzers (Beckman Industries, Fullerton, California). For the subsequent follow-up tests, the expired gas concentrations were measured every 20 seconds via indirect calorimetry using a Sensor Medics 2900 Metabolic Cart (Yorba Linda, California). All VO2max tests fulfilled the following criteria: (1) heart rate at maximal exercise 95% of the age-predicted maximal heart rate; (2) respiratory exchange ratio 1.10; and (3) VO2 reaching a plateau during the final stage of exercise (i.e., the increase in VO2 was 0.2 L · min 1 during the final increase in workload. VO2max is expressed in L · min , or in ml · kg 1 · min . During the first decade of training, there was initially a decrease in his yearly best marathon time (Figure 1). He achieved his personal best marathon time at age 51 years. His yearly best marathon race times remained fairly constant, approximately 230 minutes/ race, until age 64 years. From age 65 to 73, there was another plateau in his marathon race times. His average race time was approximately 260 minutes. There was a marked and progressive deterioration in his marathon times as he approached his ninth decade of life, due largely to the fact that he was now walking, not running during much of the marathon. The subject noted that over the 3 decades, his focus had changed from improving his marathon performance to increasing the number of marathons completed. Average weekly mileage during the first decade of training was 28 miles · week , followed by 33 miles · week 1 for the second and third decade (Figure 2). It is noteworthy that his average weekly miles of training per week peaked at 42 miles/week at age 72 years. The number of marathons completed each year increased from approximately 6/year in the first decade to 20/year in the third decade. The number of marathons run per year peaked at 38/year at age 73 (Figure 2). Between the ages of 70 and 80 years, he competed in 320 marathons. At age 81 he competed in 24 marathons. Measurements of VO2max from age 68 to age 80 are shown in Figure 3. Between ages 68 and 72 years, his VO2max was unchanged at approximately 43 ml · kg 1 · min . A marked decrease in VO2max was noted at the age 76. There was a continued decrease in From the Department of Medicine, Division of Gerontology, University of Maryland School of Medicine and Geriatrics Research Education and Clinical Center, Baltimore Veteran Affairs Medical Center, Baltimore, Maryland. This work was supported by Grant K24 AG 00930 from the National Institute on Aging; training Grant T32 AG00219 from the National Institutes of Health, Bethesda, Maryland; and a grant from the Department of Veteran Affairs Geriatric Research, Education, and Clinical Center, Washington, DC. Dr. Katzel’s address is: Baltimore VA Medical Center BT/18/GR, Baltimore, Maryland, 21201. E-mail: lkatzel@grecc.umaryland. edu. Manuscript received October 30, 2002; revised manuscript received and accepted January 13, 2003.

Body Weight, Body Composition, and Aging

One of the fastest growing segments of the population is individuals >65 years of age. This age group, which currently accounts for ∼15% of the population, is expected to grow to between 19 and 25% by 2025. Increased body fat and loss of bone mineral density (BMD) and muscle mass are defining characteristics of the aging process. These changes in body composition occur as a result of normal aging, have a detrimental effect on health status, and have substantial economic consequences on the health care system. Obesity is associated with an increased prevalence of comorbidities, including cardiovascular disease, type 2 diabetes mellitus, hypertension, dyslipidemia, and other metabolic diseases. The decline in skeletal muscle mass is associated with weakness, functional disability, frailty, and morbidity, whereas the decrease in BMD increases the risk of bone fractures and ultimately results in high rates of disability, morbidity, and mortality in the elderly. This article discusses the classification and prevalence of overweight and obesity and the changes that occur during the aging process, with emphasis on body weight, fat mass, and fat-free mass and its constituents of skeletal muscle mass, total body water, and bone. These changes in body composition are also described in context with metabolic disease states.