A Detailed Analysis of Cardiac Rehabilitation on 180-Day All-Cause Hospital Readmission and Mortality.

PURPOSE: Cardiac rehabilitation (CR) is endorsed for coronary artery disease (CAD), but studies report inconsistent findings regarding efficacy. The objective of this study was to determine whether confounding factors, potentially contributing to these heterogeneous findings, impact the effect of CR on all-cause readmission and mortality. METHODS: Patients (n = 2641) with CAD, CR eligible, and physically able were identified. Electronic medical records were inspected individually for each patient to extract demographic, clinical characteristic, readmission, and mortality information. Patients (n = 214) attended ≥1 CR session (CR group). Survival was considered free from: all-cause readmission; or composite outcome of all-cause readmission or death. Cox proportional hazards models, adjusting for demographics, comorbidities, and discharge criteria, were used to determine HR with 95% CI and to compare 180-d survival rates between the CR and no-CR groups. RESULTS: During 180 d of follow-up, 12.1% and 18.7% of the CR and non-CR patients were readmitted to the hospital. There was one death (0.5%) in the CR group, while 98 deaths (4.0%) occurred in the non-CR group. After adjustment for age, sex, race, depression, anxiety, dyslipidemia, hypertension, obesity, smoking, type 2 diabetes, and discharge criteria, the final model revealed a significant 42.7% reduction in readmission or mortality risk for patients who attended CR (HR = 0.57: 95% CI, 0.33-0.98; P = .043). CONCLUSIONS: Regardless of demographic characteristics, comorbidities, and cardiovascular discharge criteria, the risk of 180-d all-cause readmission or death was markedly decreased in patients who attended CR compared with those who did not.

Aerobic Versus Resistance Training Effects on Ventricular-Arterial Coupling and Vascular Function in the STRRIDE-AT/RT Trial.

Background: The goal was studying the differential effects of aerobic training (AT) vs. resistance training (RT) on cardiac and peripheral arterial capacity on cardiopulmonary (CP) and peripheral vascular (PV) function in sedentary and obese adults. Methods: In a prospective randomized controlled trial, we studied the effects of 6 months of AT vs. RT in 21 subjects. Testing included cardiac and vascular ultrasoundography and serial CP for ventricular-arterial coupling (Ees/Ea), strain-based variables, brachial artery flow-mediated dilation (BAFMD), and peak VO2 (pVO2; mL/kg/min) and peak O2-pulse (O2p; mL/beat). Results: Within the AT group (n = 11), there were significant increases in rVO2 of 4.2 mL/kg/min (SD 0.93) (p = 0.001); O2p of 1.9 mL/beat (SD 1.3) (p = 0.008) and the brachial artery post-hyperemia peak diameter 0.18 mm (SD 0.08) (p = 0.05). Within the RT group (n = 10) there was a significant increase in left ventricular end diastolic volume 7.0 mL (SD 9.8; p = 0.05) and percent flow-mediated dilation (1.8%) (SD 0.47) (p = 0.004). Comparing the AT and RT groups, post exercise, rVO2 2.97, (SD 1.22), (p = 0.03), O2p 0.01 (SD 1.3), (p = 0.01), peak hyperemic blood flow volume (1.77 mL) (SD 140.69) (p = 0.009), were higher in AT, but LVEDP 115 mL (SD 7.0) (p = 0.05) and Ees/Ea 0.68 mmHg/ml (SD 0.60) p = 0.03 were higher in RT. Discussion: The differential effects of AT and RT in this hypothesis generating study have important implications for exercise modality and clinical endpoints.

Cardiopulmonary Exercise Testing in the Coronavirus Disease - 2019 Era: Safety and Protocol Considerations.

ABSTRACT: Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.

Skeletal muscle capillary density is related to anaerobic threshold and claudication in peripheral artery disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. Exercise intolerance may result from reduced skeletal muscle capillary density and impaired muscle oxygen delivery. This cross-sectional study tested the hypothesis that capillary density is related to claudication times and anaerobic threshold (AT) in patients with PAD. A total of 37 patients with PAD and 29 control subjects performed cardiopulmonary exercise testing on a treadmill for AT and gastrocnemius muscle biopsies. Skeletal muscle capillary density was measured using immunofluorescence staining. PAD had decreased capillary density (278 ± 87 vs 331 ± 86 endothelial cells/mm2, p = 0.05), peak VO2 (15.7 ± 3.9 vs 24.3 ± 5.2 mL/kg/min, p ⩽ 0.001), and VO2 at AT (11.5 ± 2.6 vs 16.1 ± 2.8 mL/kg/min, p ⩽ 0.001) compared to control subjects. In patients with PAD, but not control subjects, capillary density was related to VO2 at AT (r = 0.343; p = 0.038), time to AT (r = 0.381; p = 0.020), and time after AT to test termination (r = 0.610; p ⩽ 0.001). Capillary density was also related to time to claudication (r = 0.332; p = 0.038) and time after claudication to test termination (r = 0.584; p ⩽ 0.001). In conclusion, relationships between capillary density, AT, and claudication symptoms indicate that, in PAD, exercise limitations are likely partially dependent on limited skeletal muscle capillary density and oxidative metabolism.

Effects of a 12-Week mHealth Program on FunctionalCapacity and Physical Activity in Patients With PeripheralArtery Disease.

Supervised exercise is beneficial for peripheral artery disease (PAD) patients limited by intermittent claudication (IC). However, supervised exercise for PAD remains widely underutilized. Mobile health (mHealth) provides an intermediate solution between supervised and independent home-based exercise. The purpose of this study was to determine the effects on functional capacity and physical activity patterns of a 12-week mHealth program in PAD patients with IC. Twenty patients were randomized into usual care or a 12-week mHealth intervention consisting of patient education, smartphones, and physical activity trackers. Patient education was disseminated through smartphone and a daily exercise prescription was given based on steps per day. Primary outcomes were 12-week changes in peak VO2 and claudication onset time; and changes in physical activity measured by steps per/day and minutes of exercise per/week. mHealth patients significantly increased peak VO2 from 15.2 ± 4.3 to 18.0 ± 4.8 ml/kg/min (20.3 ± 26.4%; p ≤0.05), while usual care did not change from 14.3 ± 5.4 to 14.5 ± 5.7 ml/kg/min (1.0 ± 6.9%; NS). Comparison of these changes resulted in a significant difference between groups (p ≤0.05) for peak VO2. Claudication onset time significantly increased in mHealth (320 ± 226 to 525 ± 252 seconds; ≤ 0.05), while usual care demonstrated a worsening (252 ± 256 to 231 ± 196 seconds; NS). The comparison of these group changes resulted in a significant difference (p ≤0.05). Neither steps per day or minutes of activity reached significant differences between groups. In conclusion, a 12-week mHealth program in PAD patients with IC can improve peak VO2 and claudication onset time; and mHealth interventions represent a promising alternative therapy for those patients who cannot participate in supervised exercise.

Effects of a 12-week mHealth program on peak VO2 and physical activity patterns after completing cardiac rehabilitation: A randomized controlled trial.

BACKGROUND: Site-based cardiac rehabilitation (CR) provides supervised exercise, education and motivation for patients. Graduates of CR have improved exercise tolerance. However, when participation in CR ceases, adherence to regular physical activity often declines, consequently leading to worsening risk factors and clinical events. Therefore, the purpose of this pilot study was to evaluate if a mHealth program could sustain the fitness and physical activity levels gained during CR. METHODS AND RESULTS: A 12-week mHealth program was implemented using physical activity trackers and health coaching. Twenty-five patients were randomized into mHealth or usual care after completing CR. The combination of a 4.7±13.8% increase in the mHealth and a 8.5±11.5% decrease in the usual care group resulted in a difference between groups (P≤.05) for absolute peak VO2. Usual care decreased the amount of moderate-low physical activity minutes per week (117±78 vs 50±53; P<.05) as well as moderate-high (111±87 vs 65±64; P<.05). mHealth increased moderate-high physical activity (138±113 vs 159±156; NS). The divergent changes between mHealth and usual care in moderate-high physical activity minutes/week resulted in a difference between groups (21±103 vs - 46±36; P<.05). CONCLUSIONS: A 12-week mHealth program of physical activity trackers and health coaching following CR graduation can sustain the gains in peak VO2 and physical activity achieved by site-based CR.

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training.

AIMS: To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET). METHODS: In subjects with T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by reductive chemiluminescence. All testing was repeated following 3 months of SET. RESULTS: Prior to training both groups demonstrated endothelial dysfunction, which was correlated with a net decrease in plasma nitrite following a SL-GXT (p ≤ 0.05). Following SET, the PAD-only group demonstrated an improvement in endothelial function (p ≤ 0.05) and COT (p ≤ 0.05), which was related to a net increase in plasma nitrite following the SL-GXT (both p ≤ 0.05). The T2D+PAD group had none of these increases. CONCLUSIONS: T2D in the presence of PAD attenuated improvements in endothelial function, net plasma nitrite, and COT following SET. This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET.

Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training.

The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF165b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF165b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF165b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF165b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF165b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF165b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.

Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients.

OBJECTIVE: Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. The mechanism(s) by which exercise training improves functional capacity is not understood. This study tested the hypothesis that in PAD patients who undergo supervised exercise training, increases in capillary density (CD) in calf muscle take place before improvements in peak oxygen uptake (VO(2)). METHODS AND RESULTS: Thirty-five PAD patients were randomly assigned to 12 weeks of directly supervised or home-based exercise training. Peak VO(2) testing and gastrocnemius muscle biopsies were performed at baseline and after training. CD (endothelial cells/mm(2)) was measured using immunofluorescence staining. After 3 weeks of directly supervised training, patients had an increase in CD (216±66 versus 284±77, P<0.01) but no increase in peak VO(2). However, after 12 weeks, peak VO(2) increased (15.3±2.8 versus 16.8±3.8, P<0.01), whereas in muscle, CD remained increased over baseline, but there were no changes in markers of oxidative capacity. Within subjects, CD was related to peak VO(2) before and after directly supervised training. CONCLUSION: Changes in CD in ischemic muscle with training may modulate the response to training, and those changes precede the increase in VO(2).

Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease.

The aim of this study was to determine if skeletal muscle capillary density is lower in patients with peripheral artery disease (PAD) and if capillary density relates to functional limitations. PAD patients with intermittent claudication (IC) have a decreased exercise tolerance due to exercise-induced muscle ischemia. Despite the apparent role diminished arterial flow has in this population, the degree of walking pain and functional limitation is not entirely explained by altered hemodynamics of the affected limbs. We hypothesized that skeletal muscle capillary density is lower in PAD and is related to the functional impairment observed in this population. Sixty-four patients with PAD and 56 controls underwent cardiopulmonary exercise testing and a gastrocnemius muscle biopsy. A subset of these patients (48 PAD and 47 controls) underwent peak hyperemic flow testing via plethysmography. Capillary density in PAD patients was lower compared with controls (P < 0.001). After adjustment for several baseline demographic imbalances the model relating capillary density to peak oxygen consumption (Vo(2)) remained significant (P < 0.001). In PAD subjects, capillary density correlated with peak Vo(2), peak walking time (PWT), and claudication onset time (COT). Peak hyperemic blood flow related to peak Vo(2) in both PAD and control subjects. PAD is associated with lower capillary density, and capillary density is related to the functional impairment as defined by a reduced peak Vo(2), PWT, and COT. These findings suggest that alterations in microcirculation may contribute to functional impairment capacity in PAD.

Plasma nitrite flux predicts exercise performance in peripheral arterial disease after 3months of exercise training.

Plasma nitrite is a major oxidation product of nitric oxide. It has also recently been suggested to perform an endocrine-like function as a nitric oxide donor in hypoxic tissues, allowing vasodilation. Exercise performance is limited in peripheral arterial disease because of an inadequate blood supply to working tissues. We hypothesized that exercise training in peripheral arterial disease subjects will improve "plasma nitrite flux" and endothelial function, to accompany increased exercise performance. Peripheral arterial disease subjects were tested at baseline and after 3 months supervised or home exercise training. Venous blood (arm) was drawn at rest and 10 min after a maximal graded treadmill test. Samples were added to heparin and centrifuged and plasma was snap-frozen for analysis by reductive chemiluminescence. Brachial artery endothelial function was measured in response to a hyperemic stimulus (flow-mediated dilation). At 3 months the peripheral arterial disease-supervised exercise group showed increases in claudication onset pain time (+138 s, p< or =0.05), peak walking time (+260 s, p< or =0.01), VO(2peak) (1.3 ml/kg/min, p< or =0.05), brachial artery flow-mediated dilation (+2%, p< or =0.05), and plasma nitrite flux (+33% p< or =0.05). There were no changes in the peripheral arterial disease-home exercise group. The change in plasma nitrite flux predicted the change in claudication onset pain (r(2)=0.59, p< or =0.01). These findings suggest that changes in plasma nitrite are related to endothelial function and predict exercise performance in peripheral arterial disease.

Plasma nitrite response and arterial reactivity differentiate vascular health and performance.

NO is crucial for endothelial function and vascular health. Plasma nitrite (NO(2)(-)) is the main oxidation product of NO and has been shown to reflect changes in eNOS activity. We hypothesized that plasma NO(2)(-) response to physical exercise stress along with physiological endothelial function would be reduced with increasing severity of vascular disease. Subject groups were: (a) risk factors but no vascular disease (RF); (b) Type 2 diabetes with no vascular disease (DM); (c) diagnosed peripheral arterial disease (PAD); and (d) DM+PAD. Venous blood was drawn at rest and 10min following maximal exercise. Plasma samples were analyzed by reductive chemiluminescence. Brachial diameters were imaged prior to, during and following 5min of forearm occlusion (BAFMD). There were no differences in resting plasma NO(2)(-) or BA diameters between groups. The PAD groups had lower age adjusted BAFMD responses (p0.05). Within group analysis revealed an increase in NO(2)(-) in the RF group (+39.3%), no change in the DM (-15.51%), and a decrease in the PAD (-44.20%) and PAD+DM (-39.95%). This was maintained after adjusting for age and VO(2peak) (p0.05). DeltaNO(2)(-) and BAFMD were the strongest independent predictors of VO(2peak) in multivariate linear regression. These findings suggest DeltaNO(2)(-) discriminates severity of cardiovascular disease risk, is related to endothelial function and predicts exercise capacity.

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.

The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.

A sex-specific relationship between capillary density and anaerobic threshold.

Although both capillary density and peak oxygen consumption (Vo(2)) improve with exercise training, it is difficult to find a relationship between these two measures. It has been suggested that peak Vo(2) may be more related to central hemodynamics than to the oxidative potential of skeletal muscle, which may account for this observation. We hypothesized that change in a measure of submaximal performance, anaerobic threshold, might be related to change in skeletal muscle capillary density, a marker of oxidative potential in muscle, with training. Due to baseline differences among these variables, we also hypothesized that relationships might be sex specific. A group of 21 subjects completed an inactive control period, whereas 28 subjects (17 men and 11 women) participated in a 6-mo high-intensity exercise program. All subjects were sedentary, overweight, and dyslipidemic. Potential relationships were assessed between change in capillary density with both change in Vo(2) at peak and at anaerobic threshold with exercise training. All variables and relationships were assessed for sex-specific effects. Change in peak Vo(2) was not related to change in capillary density after exercise training in either sex. Men had a positive correlation between change in Vo(2) at anaerobic threshold and change in capillary density with exercise training (r = 0.635; P < 0.01), whereas women had an inverse relationship (r = -0.636; P < 0.05) between the change in these variables. These findings suggest that, although enhanced capillary density is associated with training-induced improvements in submaximal performance in men, this relationship is different in women.

Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise.

Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time PCR from skeletal muscle biopsies collected before and approximately 24 h after the final bout of 6 mo of EE. Six months of EE led to increases in muscle lipoprotein lipase, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, carnitine palmitoyltransferase-1 beta, diacylglycerol acyltransferase-1, and acid ceramidase mRNA in women, but not men. In contrast, in men, EE led to reductions in the mRNA content of the lipogenic factors sterol regulatory element binding protein-1c and serine palmitoyl transferase. These data suggest that EE-mediated alterations in the abundance of the lipid metabolism genes studied here are fundamentally different between overweight and obese middle-aged women and men. Future studies should determine whether these adaptations in mRNA levels translate into changes in protein function.

Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease.

OBJECTIVES: Our purpose was to determine whether factors that regulate angiogenesis are altered in peripheral arterial disease (PAD) and whether these factors are associated with the severity of PAD. BACKGROUND: Alterations in angiogenic growth factors occur in cardiovascular disease (CVD), but whether these factors are altered in PAD or correlate with disease severity is unknown. METHODS: Plasma was collected from patients with PAD (n = 46) and healthy control subjects (n = 23). Peripheral arterial disease patients included those with intermittent claudication (IC) (n = 23) and critical limb ischemia (CLI) (n = 23). Plasma angiopoietin-2 (Ang2), soluble Tie2 (sTie2), vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR-1), and placenta growth factor (PlGF) were measured by enzyme-linked immunoadsorbent assay. In vitro, endothelial cells (ECs) were treated with recombinant VEGF to investigate effects on sTie2 production. RESULTS: Plasma concentrations of sTie2 (p < 0.01), Ang2 (p < 0.001), and VEGF (p < 0.01), but not PlGF or sVEGFR-1, were significantly greater in PAD patients compared with control subjects. Plasma Ang2 was significantly increased in both IC and CLI compared with control subjects (p < 0.0001), but there was no difference between IC and CLI. Plasma VEGF and sTie2 were similar in control subjects and IC but were significantly increased in CLI (p < 0.001 vs. control or IC). Increased sTie2 and VEGF were independent of CVD risk factors or the ankle-brachial index, and VEGF treatment of ECs in vitro significantly increased sTie2 shedding. CONCLUSIONS: Levels of VEGF and sTie2 are significantly increased in CLI, and sTie2 production is induced by VEGF. These proteins may provide novel biomarkers for CLI, and sTie2 may be both a marker and a cause of CLI.

Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults.

Exercise training (ET) and hormone replacement therapy (HRT) are both recognized influences on insulin action, but the influence of HRT on responses to ET has not been examined. To determine if HRT use provided additive benefits for the response of insulin action to ET, we evaluated the impact of HRT use on changes in insulin during the course of a randomized, controlled, aerobic ET intervention. Subjects at baseline were sedentary, dyslipidemic, and overweight. These individuals were randomized to 6 months of one of 3 aerobic ET interventions or continued physical inactivity. In 206 subjects, an insulin sensitivity index (S(I)) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and postintervention fitness, regional adiposity, general adiposity, skeletal muscle biochemistry and histology, and serum lipoproteins were measured as other putative mediators influencing insulin action. Two-way analyses of variance were used to determine if sex or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in S(I) differed by sex or HRT use(.) Women who used HRT (HRT+) demonstrated significantly greater improvements in S(I) with ET than women not using HRT (HRT-). In those HRT+ women, plasma triglyceride change best correlated with change in S(I). For HRT- women, capillary density change and, for men, subcutaneous adiposity change best correlated with change in S(I). In summary, in an ET intervention, HRT use appears to be associated with more robust responses in insulin action. Furthermore, relationships between ET-induced changes in insulin action and potential mediators of change in insulin action are different for men, and for women on or off HRT. These findings have implications for the relative utility of ET for improving insulin action in middle-aged men and women, particularly in the setting of differences in HRT use.

Chronic heart failure and exercise intolerance: the hemodynamic paradox.

Heart failure represents a major source of morbidity and mortality in industrialized nations. As the leading hospital discharge diagnosis in the United States in patients over the age of 65, it is also associated with substantial economic costs. While the acute symptoms of volume overload frequently precipitate inpatient admission, it is the symptoms of chronic heart failure, including fatigue, exercise intolerance and exertional dyspnea, that impact quality of life. Over the last two decades, research into the enzymatic, histologic and neurohumoral alterations seen with heart failure have revealed that hemodynamic derangements do not necessarily correlate with symptoms. This "hemodynamic paradox" is explained by alterations in the skeletal musculature that occur in response to hemodynamic derangements. Importantly, gender specific effects appear to modify both disease pathophysiology and response to therapy. The following review will discuss our current understanding of the systemic effects of heart failure before examining how exercise training and cardiac resynchronization therapy may impact disease course.

Implications of chronic heart failure on peripheral vasculature and skeletal muscle before and after exercise training.

The pathophysiology of chronic heart failure (CHF) is typically conceptualized in terms of cardiac dysfunction. However, alterations in peripheral blood flow and intrinsic skeletal muscle properties are also now recognized as mechanisms for exercise intolerance that can be modified by therapeutic exercise. This overview focuses on blood delivery, oxygen extraction and utilization that result from heart failure. Related features of inflammation, changes in skeletal muscle signaling pathways, and vulnerability to skeletal muscle atrophy are discussed. Specific focus is given to the ways in which perfusion and skeletal muscle properties affect exercise intolerance and how peripheral improvements following exercise training increase aerobic capacity. We also identify gaps in the literature that may constitute priorities for further investigation.

Exercise training amount and intensity effects on metabolic syndrome (from Studies of a Targeted Risk Reduction Intervention through Defined Exercise).

Although exercise improves individual risk factors for metabolic syndrome (MS), there is little research on the effect of exercise on MS as a whole. The objective of this study was to determine how much exercise is recommended to decrease the prevalence of MS. Of 334 subjects randomly assigned, 227 finished and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III-defined MS risk factors and were included in this analysis. Subjects were randomly assigned to a 6-month control or 1 of 3 eight-month exercise training groups of (1) low amount/moderate intensity (equivalent to walking approximately 19 km/week), (2) low amount/vigorous intensity (equivalent to jogging approximately 19 km/week), or (3) high amount/vigorous intensity (equivalent to jogging approximately 32 km/week). The low-amount/moderate-intensity exercise prescription improved MS relative to inactive controls (p <0.05). However, the same amount of exercise at vigorous intensity was not significantly better than inactive controls, suggesting that lower-intensity exercise may be more effective in improving MS. The high-amount/vigorous-intensity group improved MS relative to controls (p <0.0001), the low-amount/vigorous-intensity group (p = 0.001), and the moderate-intensity group (p = 0.07), suggesting an exercise-dose effect. In conclusion, a modest amount of moderate-intensity exercise in the absence of dietary changes significantly improved MS and thus supported the recommendation that adults get 30 minutes of moderate-intensity exercise every day. A higher amount of vigorous exercise had greater and more widespread benefits. Finally, there was an indication that moderate-intensity may be better than vigorous-intensity exercise for improving MS.