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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

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.

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.