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INTRODUCTION: Though the inverse relationship between physical activity (PA) and cardiovascular disease (CVD) is well established, observational studies suggest very high levels of PA may be harmful. This study sought to understand the relationship between PA, coronary artery calcium (CAC), and cardiovascular outcomes among individuals at different levels of risk. METHODS: PA and CAC were assessed in 6777 baseline participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Total PA in metabolic equivalents-minutes/week was categorized into quartiles, and CAC was categorized as ‘low-risk’ (

Background : Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life (QoL). Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in six minutes, 6MWD) and QoL (Kansas City Cardiomyopathy Questionnaire, KCCQ). Methods : We compared 75 older, obese, HFpEF patients to 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its three distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound) and LA reservoir strain. Results : HFpEF had decreased reservoir strain (16.4±4.4% vs. 18.2±3.5%, p=0.018), lower conduit strain (7.7±3.3% vs. 9.1±3.4%, p=0.028), and increased stiffness index (0.86±0.39 vs. 0.53±0.18, p Conclusion : LA stiffness is independently associated with impaired exercise tolerance and QoL and may be an important therapeutic target in obese HFpEF. Registration : NCT00959660

Background: We've shown that combined caloric restriction (CR) and aerobic exercise training (AT) improve peak exercise O 2 consumption (VO 2 peak); and quality-of-life (QOL) in older patients with obese heart failure with preserved ejection fraction (HFpEF). However, ~35% of weight lost during CR+AT was skeletal muscle (SM) mass. We examined whether addition of resistance training (RT) to CR+AT would reduce SM loss and further improve outcomes. Methods: Randomized, controlled, single-blind, 20-week trial of RT+CR+AT vs. CR+AT in 88 patients with chronic HFpEF and body mass index (BMI) ≥28 kg/m 2 . Outcomes at 20 weeks included: the primary outcome (VO2peak); MRI and dual X-ray absorptiometry; leg muscle strength and quality (leg strength ÷ leg SM area); Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: 77 participants completed the trial. RT+CR+AT and CR+AT produced non-significant differences in weight loss: mean (95% CI): -8(-9,-7) versus -9(-11,-8) (p=0.21). RT+CR+AT and CR+AT had non-significantly differences in the reduction of body fat [-6.5(-7.2,-5.8) versus -7.4(-8.1,-6.7) kg] and SM [-2.1(-2.7,-1.5) versus -2.1(-2.7,-1.4) kg] (p=0.20 and 0.23, respectively). RT+CR+AT produced significantly greater increases in leg muscle strength [4.9(0.7,9.0) versus -1.1(-5.5,3.2) Nm, p=0.05] and leg muscle quality [0.07(0.03,0.11) versus 0.02(-0.02,0.06) Nm/cm2, p=0.04]. Both RT+CR+AT and CR+AT produced significant improvements in VO 2 peak [108(958,157) versus 80(30,130) ml/min; p=0.001 and 0.002, respectively], and KCCQ score [17(12,22) versus 23(17,28); p=0.001 for both], with no significant between-group differences. Both RT+CR+AT and CR+AT significantly reduced LV mass and arterial stiffness. There were no study-related serious adverse events. Conclusions: In older obese HFpEF patients, CR+AT produces large improvements in VO 2 peak and QOL. Adding RT to CR+AT increased leg strength and muscle quality without attenuating SM loss or further increasing VO2peak or QOL. Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02636439

INTRODUCTION: The relationship between physical activity (PA), exercise capacity, and quality of life (QOL) in obese heart failure with preserved ejection fraction (HFpEF) is poorly understood. METHODS: This was an ancillary study to a clinical trial. Accelerometers were used to measure light PA (LPA), moderate to vigorous PA (MVPA), total PA, PA energy expenditure (PAEE), and steps. Peak VO(2), exercise time, and six-minute walk distance, as well as QOL measures were obtained. Pearson correlations were performed to examine relationships between PA, exercise capacity, and QOL. RESULTS: Patients (n=58) were 68.0±5.7 years old, 78% female, 59% white, and obese (BMI 39.1±6.1 kg/m(2)). Patients had low levels of objectively measured PA as well as reduced exercise capacity and poor QOL. LPA (r=0.32, p=0.014) and steps/day (r =0.30, p=0.022) were modestly correlated with peak VO(2). All PA variables were modestly correlated with exercise time (r=0.33–0.49, all p

OBJECTIVE Moderate- to vigorous-intensity physical activity (MVPA) improves cardiovascular health. Few studies have examined MVPA timing. We examined the associations of timing of bout-related MVPA with cardiorespiratory fitness and cardiovascular risk in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Baseline 7-day hip-worn accelerometry data from Look AHEAD participants (n = 2,153, 57% women) were analyzed to identify bout-related MVPA (≥3 METs/min for ≥10 min). Cardiorespiratory fitness was assessed by maximal graded exercise test. Participants were categorized into six groups on the basis of the time of day with the majority of bout-related MVPA (METs × min): ≥50% of bout-related MVPA during the same time window (morning, midday, afternoon, or evening), RESULTS Cardiorespiratory fitness was highly associated with timing of bout-related MVPA (P = 0.0005), independent of weekly bout-related MVPA volume and intensity. Importantly, this association varied by sex (P = 0.02). In men, the midday group had the lowest fitness (β = −0.46 [95% CI −0.87, −0.06]), while the mixed group in women was the least fit. Framingham risk score (FRS) was associated with timing of bout-related MVPA (P = 0.02), which also differed by sex (P = 0.0007). The male morning group had the highest 4-year FRS (2.18% [0.70, 3.65]), but no association was observed in women. CONCLUSIONS Timing of bout-related MVPA is associated with cardiorespiratory fitness and cardiovascular risk in men with type 2 diabetes, independent of bout-related MVPA volume and intensity. Prospective studies are needed to determine the impacts of MVPA timing on cardiovascular health.

Background: To examine the relationship between early physical activity (PA) adoption (2, 3, and 4 mo) and longer-term PA adherence (1 y) among individuals who were inactive at baseline and received a lifestyle intervention. Methods: Participants (n = 637) received weekly behavioral weight loss sessions, calorie reduction, and PA goals (50–175 min/wk progression). PA was assessed via self-reported measures at baseline, months 2 to 4, and 1 year. Results: PA at months 2 to 4 was significantly correlated with PA at 1 year (rs = .29–.35, P P P Conclusions: Failure to achieve PA goals at 2, 3, or 4 months results in less overall PA at 1 year. Thus, PA observed as early as month 2 may be a useful indicator for identifying at-risk individuals who may benefit from more intensive PA intervention strategies.

Aggressive risk factor modification, including smoking cessation, blood pressure management, and more intensive efforts to control hyperlipidemia, as well as stress management training, are associated with improved cardiovascular outcomes and impressive mortality reductions. This commentary addresses these topics, with specific reference to lifestyle modification and complementary cardioprotective medications.

PURPOSE: Although exercise training (ET) has been shown to improve both physical function and health-related quality of life (HRQOL) in older patients with heart failure and preserved ejection fraction (HFpEF), the relationship between changes in these important patient-centered outcome measures has not been adequately investigated. METHODS: Patients (n=116) with HFpEF (from two previous randomized controlled trials) were assigned to either 16-wk of endurance exercise training (ET) or attention-control (CON). The ET in both trials consisted of up to 60 minof moderate-intensity endurance ET 3 time/wk. Peak exercise oxygen uptake (VO(2peak)), and other exercise capacity measures were obtained from a cardiopulmonary exercise test on an electronically-braked cycle ergometer and 6 min walk test (6MWT). HRQOL was assessed using the Minnesota Living with Heart Failure (MLHF) Questionnaire and the Short Form Health Survey (SF-36). RESULTS: Compared to CON, the ET group demonstrated significant improvement in measures of physical function (VO(2peak) and 6MWT) at 16 wk of follow-up. There were no significant differences observed between the groups for MLHF scores, but the ET group showed significant improvements on the SF-36. There were no significant correlations between change in any of the physical function and HRQOL measures in the ET group. CONCLUSIONS: While endurance ET improved both physical function and some domains of HRQOL, the lack of significant correlations between changes in these measures suggests the effects of ET on physical function and HRQOL are largely independent of one another. Since these measures assess important and unique patient-centered outcomes in HFpEF patients, both physical function and HRQOL should be assessed in exercise-based programs and clinical trials.

Risk to individuals for cardiovascular events are invariably tied to their exposure to major coronary risk factors. This risk can be substantially mitigated by lifestyle behaviors. This first part of this Commentary focuses on the important role both adopting healthful dietary patterns and regularly obtaining adequate physical activity have as preventative therapies for cardiovascular diseases.

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of all heart failure (HF) cases and is the fastest growing form of HF in the United States. The cornerstone symptom of clinically stable HFpEF is severe exercise intolerance (defined as reduced peak exercise oxygen uptake, VO2peak) secondary to central and peripheral abnormalities that result in reduced oxygen delivery to and/or use by exercising skeletal muscle. To date, pharmacotherapy has not been shown to improve VO2peak, quality of life, and survival in patients with HFpEF. In contrast, exercise training is currently the only efficacious treatment strategy to improve VO2peak, aerobic endurance, and quality of life in patients with HFpEF. In this updated review, we discuss the specific central and peripheral mechanisms that are responsible for the impaired exercise responses as well as the role of exercise training to improve VO2peak in clinically stable patients with HFpEF. We also discuss the central and peripheral adaptations that contribute to the exercise training-mediated improvement in VO2peak in HFpEF. Finally, we provide clinical exercise physiologists with evidence-based exercise prescription guidelines to assist with the safe implementation of exercise-based cardiac rehabilitation programs in clinically stable patients with HFpEF.

Although survival rates for stage I to III breast cancer have greatly increased, in part due to improved treatment options, this progress is threatened by increased cardiovascular (CV) events for survivors. More than 35% of women experience CV injury, left ventricular (LV) dysfunction, exercise

Objectives The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. Background The marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. Methods A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. Results Over a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. Conclusions The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

Almost half of all heart failure (HF) disease burden is due to HF with preserved ejection fraction (HFpEF). The primary symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance and is associated with their reduced quality of life. Recently, studies showed that HFpEF patients have multiple skeletal muscle (SM) abnormalities, and these are associated with decreased exercise intolerance. The SM abnormalities are likely intrinsic to the HFpEF syndrome, not a secondary consequence of an epiphenomenon. These abnormalities are decreased muscle mass, reduced type I (oxidative) muscle fibers, and reduced type I-to-type II fiber ratio as well as a reduced capillary-to-fiber ratio, abnormal fat infiltration into the thigh SM, increased levels of atrophy genes and proteins, reduction in mitochondrial content, and rapid depletion of high-energy phosphate during exercise with markedly delayed repletion of high-energy phosphate during recovery in mitochondria. In addition, patients with HFpEF have impaired nitric oxide bioavailability, particularly in the microvasculature. These SM abnormalities may be responsible for impaired diffusive oxygen transport and/or impaired SM oxygen extraction. To date, exercise training (ET) and caloric restriction are some of the interventions shown to improve outcomes in HFpEF patients. Improvements in exercise tolerance following aerobic ET are largely mediated through peripheral SM adaptations with minimal change in central hemodynamics and highlight the importance of targeting SM to improve exercise intolerance in HFpEF. Focusing on the abnormalities mentioned above may improve the clinical condition of patients with HFpEF.

Cardiovascular disease (CVD) is the leading cause of death globally. Advancements in the treatment of CVD have reduced mortality rates, yet the global burden of CVD remains high. Considering that CVD is still largely a preventable disease, prioritizing preventative measures through healthy lifestyle (HL) behaviors is necessary to lessen the burden of CVD. HL behaviors, such as regular exercise, healthy eating habits, adequate sleep, and smoking cessation, can influence a number of traditional CVD risk factors as well as a less commonly measured risk factor, cardiorespiratory fitness (CRF). It is important to note that cardiac rehabilitation programs, which traditionally have focused on secondary prevention, also emphasize the importance of making comprehensive HL behavior changes. This review discusses preventative measures to reduce the burden of CVD through an increased uptake and assessment of HL behaviors. An overview of the importance of CRF as a risk factor is discussed along with how to improve CRF and other risk factors through HL behavior interventions. The role of the clinician for promoting HL behaviors to prevent CVD is also reviewed.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most rapidly increasing form of HF, occurs primarily in older women, and is associated with high rates of morbidity, mortality, and health care expenditures. In the highest age decile (≥90 years old), nearly all patients with HFpEF. As our understanding of the disease has grown in the last few years, we now know that HFpEF is a systemic disorder influenced by aging processes. The involvement of this broad collection of abnormalities in HFpEF, the recognition of the high frequency and impact of noncardiac comorbidities, and systemic, multiorgan involvement, and its nearly exclusive existence in older persons, has led to the recognition of HFpEF as a true geriatric syndrome. Most of the conventional therapeutics used in other cardiac diseases have failed to improve HFpEF patient outcomes significantly. Several recent studies have evaluated exercise training (ET) as a therapeutic management strategy in patients with HFpEF. Although these studies were not designed to address clinical endpoints, such as HF hospitalizations and mortality, they have shown that ET is a safe and effective intervention to improve peak oxygen consumption, physical function, and quality of life in clinically stable HF patients. Recently, a progressive, multidomain physical rehabilitation study among older adults showed that it is feasible in older patients with acute decompensated HF who have high frailty and comorbidities and showed improvement in physical function. However, the lack of Centers for Medicare and Medicaid Services coverage can be a major barrier to formal cardiac rehabilitation in older HFpEF patients. Unfortunately, insistence upon demonstration of mortality improvement before approving reimbursement overlooks the valuable and demonstrated benefits of physical function and life quality.

Spencer W Sullivan,1,2 Niles A Fleet,3 Vanessa A Brooks,3 Jennifer Bido,2 Benedict U Nwachukwu,2 Peter H Brubaker1 1Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC, 27106, USA; 2Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY, 10021, USA; 3Department of Sports Medicine, Wake Forest University, Winston-Salem, NC, 27106, USACorrespondence: Spencer W Sullivan 1109 Crowne Oaks Circle, Winston Salem, NC, 27106, USATel +1 317 775 2626Fax +1 646 885 8252Email spencer.sullivan44@gmail.comBackground: Bilateral leg power is being increasingly investigated as a proxy for the recovery of muscle performance after injury. Functional tests like the single leg hop for distance (SLHD) and single leg vertical jump (SLVJ) are often used to determine symmetry and return to play (RTP) readiness. As an injury predictor, leg power is accurately measured with the Keiser Air420 seated leg press.Purpose: To measure and analyze lower leg asymmetry in healthy collegiate athletes across each test battery.Methods: Eighty-eight healthy student-athletes (44 males, 44 females) across 14 varsity teams at Wake Forest University performed the SLHD, SLVJ, and the Keiser. Horizontal and vertical displacement were measured via the SLHD and SLVJ, respectively. Peak power was recorded via the Keiser Air420 leg press. Pearson correlations and repeated measures ANOVA were used to calculate associations and compare bilateral asymmetry indices (BAI) and raw scores.Results: There was a significant effect on each test’s raw BAI (P < 0.01). The mean absolute BAI were 5.42 ± 4.9%, 6.64 ± 4.9% and 5.36 ± 4.7% for the SLHD, SLVJ and Keiser, respectively. The SLVJ and Keiser (dominant leg r = 0.832, nondominant leg r = 0.826) were more highly correlated than the SLHD and Keiser (dominant leg r = 0.645, nondominant leg r = 0.687), all of which were statistically significant (P < 0.01).Conclusion: At the 90th percentile, healthy collegiate athletes attained < 15% BAI. We recommend the implementation of a battery of tests to determine normative lower limb asymmetry. A battery of functional tests may present different asymmetry indices as opposed the 10% reference asymmetry.Keywords: lower leg, power testing, functional testing, limb symmetry, athlete, return to play

BACKGROUND Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design. METHODS We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class. RESULTS Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m2 . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p

Purpose Lack of physical activity (PA) is an important risk for heart failure (HF). The objective of this study was to examine PA trends in HF and non-HF participants from a nationally representative sample of US adults from 2007 to 2016. Methods Work-related/recreational activities (min/wk) were calculated on the basis of the reported frequency, intensity, and duration, respectively. Multivariable analyses were performed using National Health and Nutrition Examination Survey data. Results Among 28 824 participants, younger (aged 18-64 yr) HF participants reported less PA time than non-HF groups, especially vigorous PA. Differences were found to be smaller in older (≥ 65 yr) participants. Overall, the percentage of younger participants who met PA guidelines was significantly lower in the HF individuals in work-related PA and total PA from 2007 to 2016 than in the non-HF participants (OR = 0.55: 95% CI, 0.39-0.59 for total PA, 0.45, 0.28-0.75 for vigorous work-related PA, and 0.68, 0.47-0.97 for moderate work-related PA, respectively). In older participants, only when considering total PA, the prevalence of meeting PA guidelines was significantly different between HF and non-HF groups (0.78, 0.62-0.98). Conclusions Self-reported PA, especially vigorous activities, is much lower in older HF participants. However, the disparity in meeting PA guidelines between those with HF and without HF is remarkable in younger individuals. Future research should focus on better understanding the psychological and physical barriers to engaging in PA among HF patients.

The anaerobic threshold (AT), obtained during cardiopulmonary exercise testing (CPET), is an important prognostic measure and can be used to develop an exercise prescription in patients after a myocardial infarction (post-MI). The purpose of this study was to examine the central and peripheral determinants of AT in post-MI patients end-tidal oxygen partial pressure (PETO2) measures. We performed cardiopulmonary exercise testing (CPET) on 148 consecutively enrolled post-MI patients to determine PETO2 measured at the AT (AT PETO2) and ΔPETO2 (difference between resting PETO2 and AT PETO2). We subsequently investigated the relationship between these measures of PETO2 and the individual AT for each patient. Multivariate linear regression analysis indicated that AT PETO2 and ΔPETO2 were independently and significantly associated with the AT (β = −0.344, p

This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese patients with heart failure with preserved ejection fraction (HFpEF), and related to decreased peak exercise oxygen uptake (peak V̇o(2)). LV strain and strain rate were measured by feature tracking of magnetic resonance cine images in 79 older obese patients with HFpEF (mean age: 66 yr; mean body mass index: 38 kg/m(2)) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures (E/e′), and correlated to peak V̇o(2). LV circumferential early diastolic strain rate was impaired in HFpEF compared with controls (0.93 ± 0.05/s vs. 1.20 ± 0.07/s, P = 0.014); however, we observed no group differences in early LV radial or longitudinal diastolic strain rates. Isolating myocardial relaxation by indexing all three early LV diastolic strain rates (i.e. circumferential, radial, and longitudinal) to E/e′ amplified the group difference in early LV diastolic circumferential strain rate (0.08 ± 0.03 vs. 0.13 ± 0.05, P < 0.0001), and unmasked differences in early radial and longitudinal diastolic strain rate. Moreover, when indexing to E/e′, early LV diastolic strain rates from all three principal strains, were modestly related with peak V̇o(2) (R = 0.36, −0.27, and 0.35, respectively, all P < 0.01); this response, however, was almost entirely driven by E/e′ itself, (R = −0.52, P < 0.001). Taken together, we found that although LV relaxation is impaired in older obese patients with HFpEF, and modestly correlates with their severely reduced peak exercise V̇o(2), LV filling pressures appear to play a much more important role in determining exercise intolerance. NEW & NOTEWORTHY Using a multimodal imaging approach to uncouple tissue deformation from atrial pressure, we found that left ventricular (LV) relaxation is impaired in older obese patients with HFpEF, but only modestly correlates with their severely reduced peak V̇o(2). In contrast, the data show a much stronger relationship between elevated LV filling pressures and exercise intolerance, refocusing future therapeutic priorities.

e24115 Background: Chemotherapy (CT) is one of the most common factors associated with fatigue among breast cancer (BC) patients. However, there is a paucity of research on the impact of different types of CT on fatigue, specifically, whether women who receive anthracycline-based (Anth) CT experience greater fatigue than those who receive non-anthracycline-based (noAnth) CT. Methods: Analyses are from the longitudinal Understanding and Predicting fatigue, cardiovascular decline, and events after BrEast cAncer sTudy (UPBEAT: WF 97415)), conducted through the NCI Community Oncology Research Program (NCORP). We compared fatigue 3-months after initiating cancer treatment, controlling for fatigue measured just prior to beginning CT (baseline), in 3 groups of women: BC patients receiving Anth CT (N = 103 at baseline), BC patients receiving NoAnth CT (N = 155), and women without cancer (N = 145). Fatigue was measured by the Functional Assessment of Chronic Illness Therapy Fatigue scale where lower scores indicate greater fatigue. Scores < 30 indicate severe fatigue. We used ANOVA and ANCOVA models (PROC GLM; SAS v. 9.4) to generate unadjusted and adjusted mean fatigue scores in the 3 groups at the relevant time point. Given that selection to CT type was not random, we further adjusted for patient characteristics that influence treatment type (stage and comorbidities) in a model with the two CT groups only. Results: Mean age of participants (75.7% White and 18.1% Black) was 53.9 years. Among BC patients, the Anth group had higher tumor stage compared to the NoAnth group. Both cancer treatment groups reported significantly greater (unadjusted) fatigue pre-chemotherapy and at 3 months than healthy controls, but did not differ from each other. Adjusting for age and baseline fatigue, 3-month fatigue scores were significantly worse for the two CT groups (32.3 for Anth group, 34.3 for the NoAnth group) compared to the controls (44.6) (p < .0001). In a model of cancer patients only, the difference between Anth and NoAnth groups remained non-significant (p = 0.10), after adjusting additionally for number of comorbidities and cancer stage. The unadjusted percentage of women with severe fatigue at 3 months was significantly greater for the BC patients (39% in the Anth group; 38% in the NoAnth group) compared to the healthy controls (1%), but again the two chemotherapy groups were not significantly different from each other. Adjustment for covariates listed above did not change this finding. Conclusions: Analyses support previous studies showing significant fatigue among BC patients treated with CT compared to women without cancer. Our data suggest that fatigue significantly impacts patients receiving CT irrespective of the regimen selected.[Table: see text]

e18696 Background: Breast cancer treatments often result in a decline in physical function that may be worsened by high levels of abdominal adipose tissue (AAT). However, the role of cardiometabolic health, which is comprised of interrelated risk factors of insulin resistance, dyslipidemia, hypertension, and central adiposity, has been infrequently addressed. Thus, we evaluated the relationship between physical function and cardiometabolic health controlling for AAT in women with breast cancer before and during receipt of potentially cardiotoxic chemotherapy. Methods: Women recruited through NCORP with stage I-III breast cancer completed a six-minute walk distance (6MWD) test to determine physical function, magnetic resonance imaging (MRI) to evaluate AAT, and assessments of cardiometabolic health before and following 3 months of chemotherapy. Specifically, MRI was used to measure waist circumference (WC), and AAT components of subcutaneous (SAT) and visceral adipose tissue (VAT). To assess cardiometabolic health, individual metabolic syndrome (MetS) components of WC, mean arterial pressure (MAP), glucose (FPG), high-density lipoprotein cholesterol (HDL), and triglycerides (TG) were used to calculate a MetS severity z-score (MetS-Z) = [(WC-88)/SD] + [(MAP-100)/SD] + [(FPG-100)/SD] + [(50-HDL)/SD] + [(TG-150)/SD]. All measures were assessed by individuals blinded to visit, demographic data, and other components of the study. Baseline and 3-month data were compared via paired t-tests. Regression analyses were used to identify the relationship between 6MWD and MetS-Z and possible mediation effects of AAT (i.e., SAT and VAT). Results: One hundred eleven women with a mean age of 56.1 ± 11.0 yrs completed assessments. After 3 months of chemotherapy, 6MWD was lower (457 ± 90.7 vs 428 ± 92.9 m, P= 0.001) and MetS-Z was increased (-1.13 ± 3.01 vs 0.30 ± 3.97 AU, P< 0.001) compared to baseline. The increase in MetS-Z was mainly attributed to elevations in TG (120 ± 81 vs 154 ± 111 mg/dl, P< 0.001) and decreases in HDL (58.6 ± 14.3 vs 47.7 ± 13.9 mg/dl, P< 0.001). No changes were observed in SAT ( P= 0.15) or VAT ( P= 0.42). Although MetS-Z was associated with 6MWD at baseline ( P= 0.01), MetS-Z was not significant predictor after controlling for SAT and VAT (B = -3.39, P= 0.34, 95% CI [-10.4, 3.62]). MetS-Z also associated wtih 6MWD at 3 months ( P= 0.002) and this remained significant after controlling for SAT and VAT (B = -5.36, P= 0.03, 95% CI [-10.3, -0.46]). Conclusions: AAT may be more strongly associated with physical function prior to chemotherapy whereas cardiometabolic traits may have clinical implications during treatment in women with breast cancer. Additional longitudinal work investigating the effects of concurrent treatments (e.g., exercise, diet, pharmacological) on the relationship between cardiometabolic health and physical function is warranted. Clinical trial information: NCT02791581.

Introduction: Physical activity is associated with decreased rates of atherosclerotic cardiovascular disease (ASCVD) and mortality. However, high levels of physical activity (PA) have paradoxically been linked with elevated levels of coronary artery calcium (CAC). It remains unclear whether high levels of physical activity in the presence of high CAC are associated with adverse outcomes in a diverse, multi-ethnic population. Hypothesis: We hypothesized that high compared to low levels of PA are associated with a reduction in incident ASCVD and all-cause mortality, even in the presence of high CAC. Methods: Baseline total PA (MET-min/week) in the Multi-Ethnic Study of Atherosclerosis (MESA), obtained via questionnaire, was divided into quartiles. CAC was dichotomized into low (CAC Results: Among the 6,814 participants included in this study, the average age was 62 years, 53% were female, and 38% were non-Hispanic white. In participants with CAC Conclusions: Our study suggests that high levels of PA are associated with a reduced risk of ASCVD and all-cause mortality among individuals with low CAC, and a reduced risk of all-cause mortality among individuals with high CAC. There was no evidence to suggest an increased risk of ASCVD from high levels of PA in individuals with high CAC.

Background: Moderate-to-vigorous physical activity (MVPA) is an important treatment in type 2 diabetes (T2D). Few studies examine the timing of MVPA, as there are no established methods to characterize the MVPA bout timing throughout the day. We determined the timing of MVPA bouts in adults with T2D, and examined whether cardiorespiratory fitness and odds of cardiovascular disease (CVD) history relate to timing of MVPA bouts in men and women. Methods: Baseline data from Look AHEAD participants (n=2153, 57% women) were analyzed. Cardiorespiratory fitness assessed by VO2max test was expressed as METs. MVPA bouts (≥3METs in ≥10mins bouts) were determined using the hip-worn RT3 accelerometer for 7 days. Participants were categorized into six groups based on the time of day with the major amount of MVPA bouts (MET-min): ≥50% of MVPA bouts during the same time window (Early morning, Late morning, Afternoon, or Evening, N=214-280/group), Results: Cardiorespiratory fitness differed by timing of MVPA bout category (P Conclusion: Higher cardiorespiratory fitness associated with evening MVPA bouts in women, and with early morning MVPA bouts in men independent of total amount of bout-MVPA. Prospective studies are needed to investigate the relationship between timing of MVPA and cardiovascular outcomes to optimize MVPA benefits in adults with T2D. Disclosure J. Qian: None. M.P. Walkup: None. S. Chen: None. P.H. Brubaker: None. D. Bond: None. P.A. Richey: None. J.M. Jakicic: Advisory Panel; Self; Weight Watchers International, Inc. K. Hu: None. F.A. Scheer: None. R. Middelbeek: None.

Introduction: Heart failure (HF) is a growing public health problem which is the leading cause of hospitalization. About half of people who develop HF die within 5 years of diagnosis. Recent evidence suggests that physical inactivity may be an important risk for HF. However, the importance of physical activity in the prevention and treatment have not been adequately recognized. Self-reported physical activity can provide insights into the impact of lifestyle behaviors on mortality. The objective of this study was to determine the relationship between physical activity and HF in a nationally representative sample of United States (US) adults. Methods: The 2007-2016 National Health and Nutrition Examination Survey data collection cycles were used for this analysis. Participants aged 65 and older with HF were defined as those who answered “yes” to the question: “Has a doctor or other health professional ever told you that you had congestive HF?” Frequency and duration of self-reported moderate-intensity (“Days moderate recreational activities” and “Minutes moderate recreational activities”) and vigorous-intensity Days vigorous recreational activities” and “Minutes vigorous recreational activities”) physical activity were collected through questionnaires as well in all data cycles. We used 2018 Physical Activity Guidelines for Americans Older Adults, which recommended that most older adults (age≥65 years) participate in at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic activity per week as our cut-off points for calculating moderate-to-vigorous physical activity. Results: Between 2007-2008 and 2015-2016, the percentage of US adults ≥65 years with HF increased from 2.76% to 3.69% (p=0.04). Although a similar percentage of participants who met the criteria of at least 150 minutes of moderate-intensity activity per week was noted in both groups from 2007 to 2016 (on average, HF: 56.9% vs. HF-free: 56.7%, respectively, p>0.05), more HF-free participants reported at least 75 minutes of vigorous-intensity recreational activities per week compared to HF participants in each calendar year (82.8% vs. 66.7%, 85.0% vs. 70.0%, 83.5% vs. 55.0%, 87.0% vs.75%, 85.2% vs. 63.6%, respectively, p Conclusions: Our findings illustrate lower self-reported physical recreational activities, especially vigorous activities, in older participants who report a diagnosis of HF and more participants without HF report vigorous-intensity recreational activities. Future study should focus on understanding the physical limitations of HF patients, which is paramount in developing cardiac rehabilitation strategies to improve their function capacity.

In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg-1 min-1 versus 14.4 ± 0.2 mL kg-1 min-1; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08).

Background and aims Physical activity (PA) levels are related to mortality and morbidity in patients with chronic heart failure (CHF). Health utility (HU), a very important cost-effectiveness analysis for health care and health status, is measured by several preference-based utility measures. This study aimed to evaluate the relation between PA and HU and the effect of disease severity on PA and HU in patients with CHF. Methods We enrolled 226 consecutive outpatients with CHF (mean age, 57.5years; males, 79.6%) in this retrospective cross-sectional study. Patients were divided into three groups by NYHA class for classification of disease severity. Patient characteristics, average step count in steps/day, PA energy expenditure (PAEE) in kcal/day for 7days as assessed by accelerometer, and HU assessed by Short Form-6D were compared between the groups. Results Average step count (r=0.37, P

Objectives To evaluate the effects of an aldosterone antagonist on exercise intolerance in older adults with heart failure and preserved ejection fraction (HFpEF). Design Randomized, placebo-controlled, double-blind trial. Setting Academic medical center, Winston-Salem, North Carolina. Participants Older adults (N = 80, aged 71 ± 1; 80% female) with stable compensated HFpEF and controlled blood pressure (BP). Measurements Participants were randomized into a 9-month treatment of spironolactone 25 mg/d vs placebo. Assessments were peak exercise oxygen consumption (VO2), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiac magnetic resonance imaging, Doppler echocardiography, and vascular ultrasound. Results Seventy-one participants completed the trial: 37 in the spironolactone group and 34 in the placebo group. Adherence according to pill count was excellent (spironolactone 95%, placebo 97%). Mean spironolactone dose was 24.3 ± 2.9 mg/d and was well tolerated. Spironolactone significantly reduced systolic and diastolic BP at rest and peak exercise. At 9-month follow-up, baseline-adjusted peak VO2, the primary outcome, was 13.5 ± 0.3 mL/kg per minute in the spironolactone group versus 13.9 ± 0.3 mL/kg per minute in the placebo group (adjusted mean difference −0.4 mL/kg per minute; 95% confidence interval = −1.1–0.4 mL/kg per minute; P = .38). The 95% confidence intervals of spironolactone's effect on peak VO2 (−8.2% to 3.2%) excluded a clinically significant beneficial effect. There were also no significant differences in 6-minute walk distance, arterial stiffness, left ventricular (LV) mass, LV mass/end-diastolic volume, or MLHFQ score. Conclusion In older adults with stable compensated HFpEF, 9 months of spironolactone 25 mg/d was well tolerated and reduced BP but did not improve exercise capacity, quality of life, LV mass, or arterial stiffness.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

The aims of the study were to evaluate the relationship between Modified Shuttle Walk Test (MSWT) with peak oxygen uptake ( V ˙ O 2peak ) in overweight/obese people with primary hypertension (HTN) and to develop an equation for the MSWT to predict V ˙ O 2peak . Participants (N = 256, 53.9 ± 8.1 years old) with HTN and overweight/obesity performed a cardiorespiratory exercise test to peak exertion on an upright bicycle ergometer using an incremental ramp protocol and the 15-level MSWT. The formula of Singh et al was used as a template to predict V ˙ O 2peak , and a new equation was generated from the measured V ˙ O 2peak -MSWT relationship in this investigation. The correlation between measured and predicted V ˙ O 2peak for Singh et al equation was moderate ( r = 0.60, P −1 minute −1 , SEE% = 21%. The correlation between MSWT and measured V ˙ O 2peak as well as for the new equation was strong ( r = 0.72, P −1 minute −1 , SEE% = 19%. These results indicate that MSWT does not accurately predict functional capacity in overweight/obese people with HTN and questions the validity of using this test to evaluate exercise intolerance. A more accurate determination from a new equation in the current study incorporating more variables from MSWT to estimate V ˙ O 2peak has been performed but still results in substantial error.

Objectives To systematically examine the relative magnitude and predictors of responses to exercise training in older adult with heart failure (HF) with reduced ejection fraction (HFrEF), and preserved EF (HFpEF). Design Secondary analysis of a randomized controlled trial. Setting Outpatient cardiac rehabilitation program. Participants Individuals with HF (24 HFrEF, 24 HFpEF) who underwent supervised exercise training. Measurements The study included individual-level data from the exercise training arms of a randomized controlled trial that evaluated the effect of 16 weeks of supervised moderate-intensity endurance exercise training in older adults with chronic, stable HFpEF and HFrEF. Changes in peak oxygen uptake (VO2peak) in response to supervised training in individuals with HFpEF were compared with that of individuals with HFrEF. The significant clinical predictors of changes in VO2peak with exercise training were assessed using univariate and multivariate regression models. Results Training-related improvement in VO2peak was higher in participants with HFpEF than in those with HFrEF (change: 18.7 ± 17.6% vs −0.3 ± 15.4%, P

Renal function (RF) and activities of daily living (ADL) are risk factors for heart failure (HF) patients. We evaluated differences in motor and cognitive ADL in relation to RF in elderly hospitalized HF patients. Participants were selected from 414 consecutive hospitalized HF patients based on certain criteria. We investigated patient characteristics including Functional Independence Measure (FIM) and estimated glomerular filtration rate (eGFR). Subjects were divided into three groups by RF level and analyzed with one-way ANOVA and Chi-square tests and two-way ANCOVA and multiple comparison tests. Of the 414 patients, 165 met the inclusion criteria (high RF: 41, moderate RF: 84, low RF: 40). There were significant differences between the three groups in age, eGFR, hemoglobin level, mobility, cognitive function, and length of hospital stay (p

Objective To evaluate the change in the 6-minute walk test (6-MWT) distance relative to changes in key functional capacity measures after 16 weeks of exercise training in older patients (≥65y) who have heart failure with preserved ejection fraction (HFpEF). Design Prospective, randomized, single-blinded (by researchers to patient group) comparison of 2 groups of HFpEF patients. Setting Hospital and clinic records; ambulatory outpatients. Participants Participants (N=47) randomly assigned to an attention control (AC) (n=24) or exercise training (ET) (n=23) group. Intervention The ET group performed cycling and walking at 50% to 70% of peak oxygen uptake ( V ˙ o 2 peak) intensity (3d/wk, 60min each session). Main Outcome Measures V ˙ o 2 peak, ventilatory threshold (VT), and 6-MWT distance were measured at baseline and after the 16-week study period. Results At follow-up, the 6-MWT distance was higher than at the baseline in both the ET (11%, P =.005) and AC (9%, P =.004) groups. In contrast, V ˙ o 2 peak and VT values increased in the ET group (19% and 11%, respectively; P =.001), but decreased in the AC group at follow-up (2% and 0%, respectively). The change in V ˙ o 2 peak versus 6-MWT distance after training was also not significantly correlated in the AC group ( r =.01, P =.95) or in the ET group ( r =.13, P =.57). The change in 6-MWT distance and VT (an objective submaximal exercise measure) was also not significantly correlated in the AC group ( r =.08, P =.74) or in the ET group ( r =.16, P =.50). Conclusions The results of this study challenge the validity of using the 6-MWT as a serial measure of exercise tolerance in elderly HFpEF patients and suggest that submaximal and peak exercise should be determined objectively by VT and V ˙ o 2 peak in this patient population.