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Background: Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. Objective: To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). Methods: CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. Results: Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = –0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = –0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. Conclusion: Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Background: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. Methods: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. Results: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (–12.5 [95% CI, –14.9 to –10.2] mm Hg) compared with SEPA(–7.1 [–95% CI, 10.4 to –3.7] mm Hg) ( P =0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (–7.0 [95% CI, –8.5 to –4.0] mm Hg), with no change in SEPA (–0.3 [95% CI, –4.0 to 3.4] mm Hg) ( P =0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus –1.1 ms/mm Hg [95% CI, –2.5 to 0.3]; P 2 [95% CI, 0.2 to 0.6] versus –0.2 ln ms 2 [95% CI, –0.5 to 0.1]; P P =0.022). There were no between-group differences in pulse wave velocity ( P =0.958) or left ventricular mass ( P =0.596). Conclusions: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02342808.

BACKGROUND Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. OBJECTIVE To examine metabolic mechanisms underlying the association between obesity and neurocognition. METHODS We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used. RESULTS Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p

ObjectiveTo determine the independent and additive effects of aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet on executive functioning in adults with cognitive impairments with no dementia (CIND) and risk factors for cardiovascular disease (CVD).MethodsA 2-by-2 factorial (exercise/no exercise and DASH diet/no DASH diet) randomized clinical trial was conducted in 160 sedentary men and women (age >55 years) with CIND and CVD risk factors. Participants were randomly assigned to 6 months of AE, DASH diet nutritional counseling, a combination of both AE and DASH, or health education (HE). The primary endpoint was a prespecified composite measure of executive function; secondary outcomes included measures of language/verbal fluency, memory, and ratings on the modified Clinical Dementia Rating Scale.ResultsParticipants who engaged in AE (d = 0.32, p = 0.046) but not those who consumed the DASH diet (d = 0.30, p = 0.059) demonstrated significant improvements in the executive function domain. The largest improvements were observed for participants randomized to the combined AE and DASH diet group (d = 0.40, p = 0.012) compared to those receiving HE. Greater aerobic fitness (b = 2.3, p = 0.049), reduced CVD risk (b = 2.6, p = 0.042), and reduced sodium intake (b = 0.18, p = 0.024) were associated with improvements in executive function. There were no significant improvements in the memory or language/verbal fluency domains.ConclusionsThese preliminary findings show that AE promotes improved executive functioning in adults at risk for cognitive decline.ClinicalTrials.gov identifierNCT01573546.Classification of evidenceThis study provides Class I evidence that for adults with CIND, AE but not the DASH diet significantly improves executive functioning.

To examine the long-term association between physical activity (PA) and psychosocial functioning following completion of cardiac rehabilitation (CR) among participants in the ENHANCED study.ENHANCED was a 3-month clinical trial examining standard CR with and without stress management training (SMT). Participants completed the Leisure-Time Exercise Questionnaire (LTEQ), Beck Depression Inventory-II (BDI-II), and the Spielberger State-Trait Anxiety Inventory (STAI) at baseline, 3- and 12-months after randomization. Prospective associations between physical activity and psychosocial function, as well as treatment group differences, were examined using repeated measures mixed modeling.One hundred nineteen participants were available at 12month follow-up. During the 12-month follow-up, PA remained higher compared to baseline (P0.001), with the majority of participants reporting that they engaged in PA on a regular basis. Depressive and anxious symptoms continued to remain lower than baseline (Ps0.001) Higher levels of PA at 12-month follow-up were associated with lower depressive (P=0.032) and anxious (P=0.003) symptoms.Higher physical activity levels following CR are associated with lower depressive and anxious symptoms. Encouraging patients to sustain higher levels of PA may promote both cardiovascular and mental health.

Objective The aim of the study was to determine the relationship of lifestyle factors and neurocognitive functioning in older adults with vascular risk factors and cognitive impairment, no dementia (CIND). Methods One hundred sixty adults (M [SD] = 65.4 [6.8] years) with CIND completed neurocognitive assessments of executive function, processing speed, and memory. Objective measures of physical activity using accelerometry, aerobic capacity determined by exercise testing, and dietary habits quantified by the Food Frequency Questionnaire and 4-Day Food Diary to assess adherence to the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets were obtained to assess direct effects with neurocognition. Potential indirect associations of high-sensitivity C-reactive protein and the Framingham Stroke Risk Profile also were examined. Results Greater aerobic capacity (β = 0.24) and daily physical activity (β = 0.15) were associated with better executive functioning/processing speed and verbal memory (βs = 0.24; 0.16). Adherence to the DASH diet was associated with better verbal memory (β = 0.17). Greater high-sensitivity C-reactive protein (βs = -0.14; -0.21) and Framingham Stroke Risk Profile (β = -0.18; -0.18) were associated with poorer executive functioning/processing speed and verbal memory. Greater stroke risk partially mediated the association of aerobic capacity with executive functioning/processing speed, and verbal memory and greater inflammation partially mediated the association of physical activity and aerobic fitness, with verbal memory. Conclusions Higher levels of physical activity, aerobic fitness, and adherence to the DASH diet are associated with better neurocognitive performance in adults with CIND. These findings suggest that the adoption of healthy lifestyle habits could reduce the risk of neurocognitive decline in vulnerable older adults. Clinical trial registration NCT01573546.

Background Moderate-to-severe kidney dysfunction is associated with atherosclerotic cardiovascular disease (ASCVD). Gradations of normal or mildly reduced kidney function may also associate with ASCVD risk. Methods We conducted a secondary analysis using baseline data from the Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE) trial. Participants were sedentary, overweight and obese adults with unmedicated pre-hypertension or Stage I hypertension and an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. The Pooled Cohorts Equations were used to estimate a 10-year risk for first ASCVD event. Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured to assess subclinical atherosclerosis and vascular endothelial function, respectively. Using linear regression, we examined the association between eGFR and ASCVD risk, IMT and FMD. Results Participants (N = 139) were predominantly women (65%), white (60%), with a mean age of 52.0 ± 9.6 years and mean eGFR of 89.1 ± 15.0 mL/min/1.73 m2. Lower eGFR of 15 mL/min/1.73 m2 was associated with higher ASCVD risk [b = −2.7% (95% confidence interval: −3.7, −1.8%), P

OBJECTIVES To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention. DESIGN A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial. SETTING Academic tertiary care medical center. PARTICIPANTS Volunteer sample of 160 older sedentary adults with CIND and at least one additional CVD risk factor enrolled in the ENLIGHTEN trial between December 2011 and March 2016. INTERVENTIONS Six months of aerobic exercise (AE), DASH diet counseling, combined AE + DASH, or health education (HE) controls. MEASUREMENTS Neurocognitive battery recommended by the Neuropsychological Working Group for Vascular Cognitive Disorders including measures of executive function, memory, and language/verbal fluency. Secondary outcomes included the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Six-Minute Walk Distance (6MWD), and CVD risk including blood pressure, body weight, and CVD medication burden. RESULTS Despite discontinuation of lifestyle changes, participants in the exercise groups retained better executive function 1 year post-intervention (P = .041) compared with non-exercise groups, with a similar, albeit weaker, pattern in the DASH groups (P = .054), without variation over time (P's > .867). Participants in the exercise groups also achieved greater sustained improvements in 6MWD compared with non-Exercise participants (P

The kidney is an important regulator of blood pressure (BP). To determine whether BP response to lifestyle modification varies across normal ranges of kidney function, the authors examined the moderating role of estimated glomerular filtration rate (eGFR) on clinic and ambulatory systolic BP (SBP) response in overweight and obese adults with unmedicated high BP. Among 144 participants of the Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE) trial, mean age was 52.0±9.6 years and median eGFR was 89.1 (53–146) mL/min/1.73m(2). After multivariable regression, the interaction between eGFR and weight loss was significant for clinic (P=.023) and ambulatory SBP (P=.041). Similarly, the interaction between eGFR and improved fitness was significant for clinic (P=.041) and ambulatory SBP (P=.044). The relationship between reduced dietary sodium and SBP was not moderated by eGFR. SBP findings were inconsistent for adherence to the Dietary Approaches to Stop Hypertension (DASH) diet. These findings suggest that the effects of lifestyle modifications on SBP may be influenced by eGFR, even when kidney function is preserved.

Background— Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results— One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone ( P =0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25–0.95; P =0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27–0.71; P Conclusions— CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00981253.

OBJECTIVE To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. METHODS Three hundred twenty-six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life and were followed up for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. RESULTS Sixty-nine individuals experienced a hospitalization or died over a mean follow-up period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (hazard ratio [HR] = 2.72 [95% confidence interval = 1.63-4.54], per stage); 6-minute walk (HR = 0.50 [0.34-0.73] per 500 ft), total steps (HR = 0.82 [0.71-0.94] per 1000 steps), high-sensitivity C-reactive protein (HR = 1.44 [1.01-2.06] per 4.5 mg/l), depression (HR = 1.12 [1.01-1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14-2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and 6-minute walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. CONCLUSIONS Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD.

Background Impaired functional capacity and emotional distress are associated with lower quality of life (QoL) and worse clinical outcomes in post lung transplant patients. Strategies to increase physical activity and reduce distress are needed. Methods The Investigational Study of Psychological Interventions in Recipients of Lung Transplant-III study is a single site, parallel group randomized clinical trial in which 150 lung transplant recipients will be randomly assigned to 3 months of telephone-delivered coping skills training combined with aerobic exercise (CSTEX) or to a Standard of Care plus Education control group. The primary endpoints are a global measure of distress and distance walked on the 6-Minute Walk Test. Secondary outcomes include measures of transplant-specific QoL, frailty, health behaviors, and chronic lung allograft dysfunction-free survival. Results Participants will be evaluated at baseline, at the conclusion of 3 months of weekly treatment, at 1-year follow-up, and followed annually thereafter for clinical events for up to 4 years (median = 2 y). We also will determine whether functional capacity, distress, and health behaviors (eg, physical activity, medication adherence, and volume of air forcefully exhaled in 1 second (FEV1), mediate the effects of the CSTEX intervention on clinical outcomes. Conclusions Should the CSTEX intervention result in better outcomes compared with the standard of care plus post-transplant education, the remotely delivered CSTEX intervention can be made available to all lung transplant recipients as a way of enhancing their QoL and improving clinical outcomes.

Objectives The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease. Background Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined. Methods One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50–200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function. Results After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean −7.5; 95% confidence interval: −9.8 to −5.0) and sertraline (mean −6.1; 95% confidence interval: −8.4 to −3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean −4.5; 95% confidence interval: −7.6 to −1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093). Conclusions Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068 )

Background Performance status (PS) scoring systems are tools of immense clinical importance in the management of patients with malignant disease but these tools are subjective and do not provide an objective evaluation of physical functioning. We conducted a pilot study to explore the feasibility and clinical utility of functional capacity testing to assess physical functioning in recurrent primary malignant glioma patients. Patients and methods Using a cross-sectional design, consecutive patients with recurrent glioma performed a six minute walk (6MW) test to assess functional capacity. Performance status was assessed using Karnofsky Performance Status (KPS) scoring system. QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale. Self-reported exercise behavior was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ). Results A total of 171 patients were recruited and tested. Seventy percent were diagnosed with glioblastoma multiforme (WHO grade IV) and 85% were undergoing therapy. Median KPS was 90% (range, 70–100%). Median 6MW distance was 400 m (range, 102–630 m), equivalent to 56 ± 13% (range, 14–87%) of that predicted for age and sex. KPS, self-reported exercise, and QOL increased across 6MW distance quartiles (P

BACKGROUND. A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted. METHODS. Using a single-group design, 20 patients with stage I-IIIB NSCLC performed 3 aerobic cycle ergometry sessions per week at 60% to 100% of peak workload for 14 weeks. Peak oxygen consumption (VO2peak) was assessed using an incremental exercise test. QOL and fatigue were assessed using the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale. RESULTS. Nineteen patients completed the study. Intention-to-treat analysis indicated that VO2peak increased 1.1 mL/kg 21 /min 21 (95% confidence interval [CI], 20.3-2.5; P 5 .109) and peak workload increased 9 W (95% CI, 3-14; P 5 .003), whereas FACT-L increased 10 points (95% CI, 21-22; P 5 .071) and fatigue decreased 7 points (95% CI; 2 1t o217; P 5 .029) from baseline to postintervention. Per protocol analyses indicated greater improvements in cardiopulmonary and QOL endpoints among patients not receiving adjuvant chemotherapy. CONCLUSIONS. This pilot study provided proof of principle that supervised aerobic training is safe and feasible for postsurgical NSCLC patients. Aerobic exercise training is also associated with significant improvements in QOL and select cardiopulmonary endpoints, particularly among patients not receiving chemotherapy. Larger randomized trials are warranted. Cancer 2008;113:3430–9. � 2008 American Cancer Society.

Background Resistant hypertension (RH) is a growing health burden in this country affecting as many as 1 in 5 adults being treated for hypertension. Resistant hypertension is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure (BP) in this high-risk population are a national priority. Methods TRIUMPH is a single-site, prospective, randomized clinical trial to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie Dietary Approaches to Stop Hypertension eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (n = 150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic BP; secondary end points include ambulatory BP and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, BP, and CVD risk factors also will be measured at 1-year follow-up. Conclusions The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on BP and CVD biomarkers in patients with RH after 4 months of treatment and will determine whether lifestyle changes can be maintained for a year.

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown.To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group.Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality.Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002).Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life (QoL). Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic QoL and on the combined medical end point of COPD-related hospitalizations and all-cause mortality.We conducted a dual-site, randomized clinical trial with assessments at baseline and after 16 weeks of treatment. The study population comprised 326 outpatients with COPD aged 38 to 81 years, randomized to coping skills training (CST) or to COPD education (COPD-ED). Patients completed a battery of QoL instruments, pulmonary function tests, and functional measures and were followed up for up to 4.4 years to assess medical outcomes.The CST group exhibited greater improvements in psychological QoL compared with controls (p = .001), including less depression (Cohen d = 0.22 [95% confidence interval, or CI = 0.08-0.36]) and anxiety (d = 0.17 [95% CI = 0.02-0.33]), and better overall mental health (d = 0.17 [95% CI = 0.03-0.32]), emotional role functioning (d = 0.29 [95% CI = 0.10-0.48]), vitality (d = 0.27 [95% CI = 0.11, 0.42]), and social functioning (d = 0.21 [95% CI = 0.03-0.38]). A significant baseline psychological QoL by treatment group interaction revealed that CST with lower QoL at baseline achieved even greater improvements in psychological QoL compared with COPD-ED. CST participants also exhibited greater improvements in somatic QoL (p = .042), including greater improvements in pulmonary QoL (d = 0.13 [95% CI = 0.01-0.24]), less fatigue (d = 0.34 [95% CI = 0.18-0.50]), and less shortness of breath (d = 0.11 [95% CI = -0.01 to 0.23]) and greater improvement in distance walked on the Six-Minute Walk test (d = 0.09 [95% CI = 0.01-0.16]). However, there was no significant difference in risk of time to COPD-related hospitalization or all-cause mortality between CST (34 events) and COPD-ED (32 events; p = 0.430).A telehealth CST intervention produced clinically meaningful improvements in QoL and functional capacity, but no overall improvement in risk of COPD-related hospitalization and all-cause mortality.clinicaltrials.gov Identifier: NCT00736268.

Objectives: To examine the association of anxiety and depression with pulmonary-specific symptoms of Chronic Obstructive Pulmonary Disease (COPD), and to determine the extent to which disease severity and functional capacity modify this association. Method: Patients ( N = 162) enrolled in the INSPIRE-II study, an ongoing randomized, clinical trial of COPD patients and their caregivers who received either telephone-based coping skills training or education and symptom monitoring. Patients completed a psychosocial test battery including: Brief Fatigue Inventory, St. George's Respiratory Questionnaire, UCSD Shortness of Breath Questionnaire, State-Trait Anxiety Inventory, and Beck Depression Inventory. Measures of disease severity and functional capacity (i.e., FEV1 and six-minute walk test) were also obtained. Results: After covariate adjustment, higher anxiety and depression levels were associated with greater fatigue levels ( ps < .001, ΔR2 = 0.16 and 0.29, respectively), shortness of breath ( ps < .001, ΔR2 = 0.12 and 0.10), and frequency of COPD symptoms ( ps < .001, ΔR2 = 0.11 and 0.13). In addition, functional capacity was a moderator of anxiety and pulmonary-specific COPD symptoms. The association between anxiety and shortness of breath ( p = 0.009) and frequency of COPD symptoms ( p = 0.02) was greater among patients with lower functional capacity. Conclusions: Anxiety and depression were associated with higher levels of fatigue, shortness of breath, and frequency of COPD symptoms. It is important for clinicians to be aware of the presence of anxiety and depression in COPD patients, which appears to correlate with pulmonary-specific COPD symptoms, especially in patients with lower functional capacity. Prospective design studies are needed to elucidate the causal relationships between anxiety and depression and pulmonary-specific symptoms in COPD patients.

The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease.Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined.One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function.After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: -9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% confidence interval: -7.6 to -1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093).Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068).

Purpose. To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. Methods. Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO2peak) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy–Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. Results. Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO2peak and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). Conclusions. Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.

BACKGROUND: The study was undertaken to evaluate cardiorespiratory fitness, skeletal muscle function, and body composition of patients with newly diagnosed and untreated, postsurgical primary malignant glioma. METHODS: By using a cross-sectional design, patients with clinically stable (10 ± 7 days postsurgery) high-grade glioma (HGG; n = 25) or low-grade glioma (LGG; n = 10) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess cardiorespiratory fitness (peak oxygen consumption, VO2peak). Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain scale. RESULTS: CPET was a feasible and safe procedure to assess VO2peak, with no serious adverse events. VO2peak indexed to total body weight and lean body mass (LBM) for both groups was 13.0 mL · weight · min−1 and 19 mL · LBM · min−1, the equivalent to 59% and 38% below age- and sex-predicted normative values, respectively. Skeletal muscle strength and mid-thigh CSA were lower in HGG relative to LGG patients (83 vs 125 Nm, P = .025; 94 vs 119 cm2, P = .171, respectively). Skeletal muscle isokinetic strength, CSA, and body composition outcomes predicted VO2peak (r = −0.59 to 0.68, P < .05). CONCLUSIONS: Postsurgical glioma patients have markedly reduced cardiorespiratory fitness, isokinetic strength, and CSA. Prospective studies are now required to determine whether such abnormalities influence treatment toxicity and clinical outcome as well as to test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. Cancer 2010. © 2009 American Cancer Society.

Small LDL and HDL particle size are characteristic of a proatherogenic lipoprotein profile. Aerobic exercise increases these particle sizes. Although visceral adipose tissue (VAT) has been strongly linked with dyslipidemia, the importance of intermuscular adipose tissue (IMAT) to dyslipidemia and exercise responses is less well understood. We measured exercise-associated changes in thigh IMAT and VAT and examined their relationships with changes in LDL and HDL particle size. Sedentary, dyslipidemic, overweight subjects ( n = 73) completed 8–9 mo of aerobic training. Linear regression models were used to compare the power of IMAT change and VAT change to predict lipoprotein size changes. In men alone ( n = 40), IMAT change correlated inversely with both HDL size change ( r = −0.42, P = 0.007) and LDL size change ( r = −0.52, P < 0.001). That is, reduction of IMAT was associated with a shift toward larger, less atherogenic lipoprotein particles. No significant correlations were observed in women. After adding VAT change to the model, IMAT change was the only significant predictor of either HDL size change ( P = 0.034 for IMAT vs. 0.162 for VAT) or LDL size change ( P = 0.004 for IMAT vs. 0.189 for VAT) in men. In conclusion, in overweight dyslipidemic men, exercise-associated change in thigh IMAT was inversely correlated with both HDL and LDL size change and was more predictive of these lipoprotein changes than was change in VAT. Reducing IMAT through aerobic exercise may be functionally related to some improvements in atherogenic dyslipidemia in men.

e13002 Background: The neuropsychological impact of malignant glioma is well documented; the physiological and functional effects are not known. We conducted a pilot study to quantitatively assess cardiorespiratiory fitness, skeletal muscle function, and body composition of patients with primary malignant glioma. Methods: Using a cross-sectional design, patients with clinically stable postsurgical (10 ± 7 days post surgery) high-grade glioma (HGG; n=25) and low-grade glioma (LGG) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess peak exercise capacity (VO2peak) and other parameters of cardiovascular function. Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale (FACT-BR). Results: CPET was a feasible and safe procedure for malignant glioma patients with no serious adverse events. Peak VO2 indexed to total body weight and lean body mass for both groups was 13.0 mL.min-1 and 19 mL.min-1; the equivalent to 59% and 38% below age and sex-predicted normative values, respectively. Skeletal muscle isokinetic strength was significantly lower in HGG relative to LGG patients (83 vs. 125 Nm, p=.025) and predicted peak VO2 (r = 0.44, p2peak (r = -0.40; p=.052) were associated with fatigue. Conclusions: CPET is a safe and feasible tool to evaluate physical functioning in select patients with malignant glioma. Postsurgical glioma patients have markedly reduced exercise capacity, isokinetic strength and CSA. Muscle strength is an important contributor to poor VO2peak in this population. Prospective studies are now required to determine whether such abnormalities influence prognosis as well as test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. No significant financial relationships to disclose.

7577 Background: The effects of standard NSCLC adjuvant therapy (i.e., pulmonary resection, adjuvant chemotherapy) together with deconditioning secondary to treatment has a profound negative impact...