Research Goes Red: Early Experience With a Participant-Centric Registry.

RATIONALE: Cardiovascular disease remains the leading cause of death in women. To address its determinants including persisting cardiovascular risk factors amplified by sex and race inequities, novel personalized approaches are needed grounded in the engagement of participants in research and prevention. OBJECTIVE: To report on a participant-centric and personalized dynamic registry designed to address persistent gaps in understanding and managing cardiovascular disease in women. METHODS AND RESULTS: The American Heart Association and Verily launched the Research Goes Red registry (RGR) in 2019, as an online research platform available to consenting individuals over the age of 18 years in the United States. RGR aims to bring participants and researchers together to expand knowledge by collecting data and providing an open-source longitudinal dynamic registry for conducting research studies. As of July 2021, 15 350 individuals have engaged with RGR. Mean age of participants was 48.0 48.0±0.2 years with a majority identifying as female and either non-Hispanic White (75.7%) or Black (10.5%). In addition to 6 targeted health surveys, RGR has deployed 2 American Heart Association-sponsored prospective clinical studies based on participants' areas of interest. The first study focuses on perimenopausal weight gain, developed in response to a health concerns survey. The second study is designed to test the use of social media campaigns to increase awareness and participation in cardiovascular disease research among underrepresented millennial women. CONCLUSIONS: RGR is a novel online participant-centric platform that has successfully engaged women and provided critical data on women's heart health to guide research. Priorities for the growth of RGR are centered on increasing reach and diversity of participants, and engaging researchers to work within their communities to leverage the platform to address knowledge gaps and improve women's health.

Cardiovascular disease in adolescent and young adult cancer survivors: Impact of sociodemographic and modifiable risk factors.

BACKGROUND: There is a growing population of adolescent and young adult (AYA) cancer survivors (ages 15-39 years), and they have an elevated risk of developing cardiovascular disease (CVD). Little is known about the contribution of sociodemographic and modifiable factors to the risk of CVD in AYA survivors and whether these factors differentially modulate their risk compared with that in the general population. The current study sought to fill these gaps. METHODS: Self-reported data from the US National Health Interview Survey (2009-2018) were used to identify AYA cancer survivors (≥2 years postdiagnosis) and age-matched and sex-matched controls. The risk of CVD based on sociodemographic factors (sex, race/ethnicity, income, education) and modifiable risk factors (diabetes, body mass index, smoking, physical activity) was determined within and between survivors and controls using logistic regression models. RESULTS: In total, 4766 AYA cancer survivors and 47,660 controls were included. The odds of CVD were significantly higher in survivors than in controls by sex, race/ethnicity, income, education, smoking status, and physical activity. An annual household income <$50,000 disproportionately increased the odds of CVD in survivors. One third of survivors reported no moderate-to-vigorous-intensity physical activity (MVPA). Performing any MVPA lowered the odds of CVD in survivors (odds ratio, 0.61; 95% CI, 0.450.81) and controls (odds ratio, 0.68; 95% CI, 0.61-0.77). CONCLUSIONS: Sociodemographic and modifiable risk factors increased the odds of CVD in AYA survivors, in some cases disproportionately, compared with controls. Understanding health behavior trajectories among different sociodemographic populations is needed to identify opportunities to lower the risk of CVD. Performing any MVPA is particularly important for AYA survivors.

Salutary effects of moderate but not high intensity aerobic exercise training on the frequency of peripheral T-cells associated with immunosenescence in older women at high risk of breast cancer: a randomized controlled trial.

BACKGROUND: Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer 'senescent' and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate 'older looking' T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.e. 'myokines') IL-6, IL-7, IL-15 and osteonectin in older women at high risk of breast cancer. The intervention involved 3 sessions/week of either high intensity interval exercise (HIIT) or moderate intensity continuous exercise (MICT) and were compared to an untrained control (UC) group. RESULTS: HIIT decreased total granulocytes, CD4+ T-cells, CD4+ naïve T-cells, CD4+ recent thymic emigrants (RTE) and the CD4:CD8 ratio after training, whereas MICT increased total lymphocytes and CD8 effector memory (EM) T-cells. The change in total T-cells, CD4+ naïve T-cells, CD4+ central memory (CM) T-cells and CD4+ RTE was elevated after MICT compared to HIIT. Changes in [Formula: see text] after training, regardless of exercise prescription, was inversely related to the change in highly differentiated CD8+ EMRA T-cells and positively related to changes in ß2-adrenergic receptor (ß2-AR) expression on CM CD4+ and CM CD8+ T-cells. Plasma myokine levels did not change significantly among the groups after training, but individual changes in IL-7 were positively related to changes in the number of ß2-AR expressing CD4 naïve T cells in both exercise groups but not controls. Further, CD4 T-cells and CD4 naive T-cells were negatively related to changes in IL-6 and osteonectin after HIIT but not MICT, whereas CD8 EMRA T-cells were inversely related to changes in IL-15 after MICT but not HIIT. CONCLUSIONS: Aerobic exercise training alters the frequency of peripheral T-cells associated with immunosenescence in middle aged/older women at high risk of breast cancer, with HIIT (pro-senescent) and MICT (anti-senescent) evoking divergent effects. Identifying the underlying mechanisms and establishing whether exercise-induced changes in peripheral T-cell numbers can alter the risk of developing breast cancer warrants investigation.

The impact of high-intensity interval exercise training on NK-cell function and circulating myokines for breast cancer prevention among women at high risk for breast cancer.

PURPOSE: Preclinical evidence suggests that natural killer cell (NK-cell) function and myokines facilitate the protective effects of exercise for breast cancer prevention. Since higher-intensity exercise acutely promotes greater mobilization and larger changes in NK-cell cytotoxicity than lower-intensity, high-intensity interval training (HIIT) might offer increased immune protection compared to moderate-intensity continuous-training (MICT). This study compared a 12-week HIIT program to a 12-week MICT program and usual care on changes in resting NK-cell function and circulating myokines among women at high risk for breast cancer. METHODS: Thirty-three women were randomized to HIIT, MICT, or usual care, for a supervised exercise intervention. Blood was collected at baseline and end-of-study. The cytotoxic activity of CD3-/CD56+ NK-cells against the K562 target cell line in vitro was determined by flow cytometry. Circulating myokines (IL-15, IL-6, irisin, OSM, osteonectin, IL-7) were assessed with luminex multiplex assays and ELISA. One-way ANOVA and paired sample t-tests assessed between- and within-group differences, respectively. Pearson correlation coefficients determined relationships between baseline fitness and change variables. RESULTS: Significant differences were not observed between groups for change in NK-cell function or circulating myokines (p > 0.05). Significant correlations were only observed for baseline peak aerobic capacity (ml/kg/min) and change in NK-cell-specific lysis (r = - 0.43, p = 0.02) and hemacytotoxicity for the total sample (r = - 0.46, p = 0.01). CONCLUSION: Our findings suggest that exercise intensity may not significantly impact change in resting NK-cell function and circulating myokines among women at high risk for breast cancer. Structured exercise training may have a larger impact on NK-cell function in those with lower levels of cardiorespiratory fitness. CLINICAL TRIAL REGISTRATION: NCT02923401; Registered on October 4, 2016.

Exercise testing and cardiac rehabilitation in patients treated for cancer.

Cardiovascular disease (CVD) is a major competing cause of morbidity and mortality in patients with cancer. Cancer treatment can have detrimental short- and long-term cardiovascular effects. Moreover, cancer patients may have a significant loss in cardiorespiratory fitness, a key CVD risk factor, during and after cancer treatment. Exercise training has emerged as a potential intervention to improve fitness and reduce the risk of CVD in cancer. In this review, we discuss the role of cardiorespiratory fitness to predict cancer and CVD outcomes, as well as explore the impact of exercise training to improve fitness and other key outcomes in patients with cancer. The role of cardio-oncology rehabilitation will also be highlighted.

Cardio-Oncology Rehabilitation to Manage Cardiovascular Outcomes in Cancer Patients and Survivors: A Scientific Statement From the American Heart Association.

Cardiovascular disease is a competing cause of death in patients with cancer with early-stage disease. This elevated cardiovascular disease risk is thought to derive from both the direct effects of cancer therapies and the accumulation of risk factors such as hypertension, weight gain, cigarette smoking, and loss of cardiorespiratory fitness. Effective and viable strategies are needed to mitigate cardiovascular disease risk in this population; a multimodal model such as cardiac rehabilitation may be a potential solution. This statement from the American Heart Association provides an overview of the existing knowledge and rationale for the use of cardiac rehabilitation to provide structured exercise and ancillary services to cancer patients and survivors. This document introduces the concept of cardio-oncology rehabilitation, which includes identification of patients with cancer at high risk for cardiac dysfunction and a description of the cardiac rehabilitation infrastructure needed to address the unique exposures and complications related to cancer care. In this statement, we also discuss the need for future research to fully implement a multimodal model of cardiac rehabilitation for patients with cancer and to determine whether reimbursement of these services is clinically warranted.

Opportunities for improved cardiovascular disease prevention in oncology patients.

PURPOSE OF REVIEW: Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population. RECENT FINDINGS: Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors. SUMMARY: A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials.

Diet, weight management, physical activity and Ovarian & Breast Cancer Risk in women with BRCA1/2 pathogenic Germline gene variants: systematic review.

INTRODUCTION: Women with pathogenic germline gene variants in BRCA1 and/or BRCA2 are at increased risk of developing ovarian and breast cancer. While surgical and pharmacological approaches are effective for risk-reduction, it is unknown whether lifestyle approaches such as healthful dietary habits, weight management, and physical activity may also contribute to risk-reduction. We conducted a systematic review of evidence related to dietary habits, weight status/change, and physical activity on ovarian and breast cancer risk among women with BRCA1/2 pathogenic variants. METHODS: We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21. RESULTS: There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk. CONCLUSIONS: There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women with BRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same.

Cardiorespiratory Fitness, Coronary Artery Calcium, and Cardiovascular Disease Events in a Cohort of Generally Healthy Middle-Age Men: Results From the Cooper Center Longitudinal Study.

BACKGROUND: A robust literature demonstrates that coronary artery calcification (CAC) and cardiorespiratory fitness (CRF) are independent predictors of cardiovascular disease (CVD) events. Much less is known about the joint associations of CRF and CAC with CVD risk. In the setting of high CAC, high versus low CRF has been associated with decreased CVD events. The goal of this study was to assess the effect of continuous levels of CRF on CVD risk in the setting of increasing CAC burden. METHODS: We studied 8425 men without clinical CVD who underwent preventive medicine examinations that included an objective measurement of CRF and CAC between 1998 and 2007. There were 383 CVD events during an average follow-up of 8.4 years. Parametric proportional hazards regression models based on a Gompertz mortality rule were used to estimate total CVD incidence rates at 70 years of age as well as hazard ratios for the included covariates. RESULTS: CVD events increased with increasing CAC and decreased with increasing CRF. Adjusting for CAC level (scores of 0, 1-99, 100-399, and ≥400), for each additional MET of fitness, there was an 11% lower risk for CVD events (hazard ratio, 0.89; 95% confidence interval, 0.84-0.94). When CAC and CRF were considered together, there was a strong association between continuous CRF and CVD incidence rates in all CAC groups. CONCLUSIONS: In a large cohort of generally healthy men, there is an attenuation of CVD risk at all CAC levels with higher CRF.

The association between post-diagnosis health behaviors and long-term quality of life in survivors of ductal carcinoma in situ: a population-based longitudinal cohort study.

PURPOSE: Women diagnosed with ductal carcinoma in situ (DCIS) often experience adverse changes in health-related behaviors following diagnosis. The impact of health behaviors on long-term quality of life (QoL) in DCIS survivors has not been investigated. METHODS: We examined the association of post-diagnosis body mass index (BMI), physical activity, alcohol, and smoking with QoL among 1448 DCIS survivors aged 20-74 enrolled in the population-based Wisconsin in situ Cohort from 1997 to 2006. Health behaviors and QoL were self-reported during biennial post-diagnosis interviews. Physical and mental QoL were measured using the validated SF-36 questionnaire. Generalized linear regression was used to determine the association between behaviors and QoL with adjustment for confounders. Lagged behavior variables were used to predict QoL during follow-up and avoid reverse causation. RESULTS: Women reported 3,536 QoL observations over an average 7.9 years of follow-up. Women maintaining a healthy BMI had on average a significantly higher summary measure score of physical QoL than obese women (normal versus obese: ß = 3.02; 2.18, 3.85). Physical QoL scores were also elevated among those who were physically active (5 + h/week vs. none: ß = 1.96; 0.72, 3.20), those consuming at least seven drinks/week of alcohol (vs. none; ß = 1.40; 0.39, 2.41), and nonsmokers (vs. current smokers: ß = 1.80; 0.89, 2.71). Summary measures of mental QoL were significantly higher among women who were moderately physically active (up to 2 h/week vs. none: ß = 1.11; 0.30, 1.92) and nonsmokers (vs. current smokers: ß = 1.49;0.45, 2.53). CONCLUSIONS: Our results demonstrate that maintaining healthy behaviors following DCIS treatment is associated with modest improvements in long-term QoL. These results inform interventions aimed at promoting healthy behaviors and optimizing QoL in DCIS survivors.

Cardiovascular Disease in Childhood, Adolescent, and Young Adult Cancer Survivors: The Impact of Family History of Premature Heart Disease.

Purpose: Childhood, adolescent, and young adult (CAYA) cancer survivors (age 0-39 years at diagnosis) are at increased risk of cardiovascular disease (CVD). Family history of early heart disease increases the risk of CVD in the general population; however, it is unknown whether this association is seen in CAYA cancer survivors. Methods: Self-report data from the National Health and Nutrition Examination Survey (2005-2018) were used to identify CAYA survivors (>5 years post-diagnosis). The risk of CVD based on family history status (parent or sibling with a diagnosis of heart attack or angina before age 50 years), personal sociodemographic factors, personal medical history factors, and personal behavioral risk factors was determined using logistic regression models. Results: Included were 95 CAYA survivors with CVD and 491 CAYA survivors without CVD. The odds of CVD were significantly higher in survivors with a first-degree family history of early heart disease (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.14-3.74). A history of diabetes (OR: 2.61, 95% CI: 1.41-4.84), hypertension (OR: 1.81, 95% CI: 1.04-3.16), and any smoking (OR: 2.19, 95% CI: 1.19-4.02) was also associated with higher odds of CVD in CAYA survivors. Reporting any physical activity in the past month was associated with lower odds (OR: 0.54, 95% CI: 0.30-0.97) of CVD. Conclusions: Family history of early heart disease was associated with increased odds of CVD in CAYA cancer survivors. Obtaining complete and accurate family history information is important both at time of diagnosis and throughout follow-up.

Disparities in physical activity in adolescent and young adult cancer survivors.

PURPOSE: There is a growing population of adolescent and young adult (AYA, ages 15-39 at diagnosis) cancer survivors at heightened risk of chronic conditions. Moderate to vigorous physical activity level (MVPA) is an important modifiable factor associated with improved cardiovascular health. Little is known about the association of sociodemographic factors with MVPA in AYA survivors. METHODS: Self-reported data from the National Health Interview Survey (2009-2018) were used to identify AYA cancer survivors (at least 2 years post-diagnosis) and age- and sex-matched controls. MVPA level based on sociodemographic (sex, race and ethnicity, income, education), medical (heart disease, stroke, and diabetes), and cardiovascular risk factors (BMI and smoking) was determined within and between survivors and controls using multivariable linear regression models. RESULTS: A total of 4766 AYA cancer survivors and 47,660 controls were included. Less than half of survivors (41.9%) and controls (43.2%) met MVPA guideline recommendations, and one-third of survivors (33.4%) reported no MVPA. Black race was associated with reduced MVPA compared with White race (ratio: 0.58 (95% CI: 0.37-0.90). Household income < $50,000/year, education < high school, diagnoses of diabetes or heart disease, and current smoking were all significantly associated with reduced MVPA in AYA survivors. There were no differences in MVPA between survivors and controls by sociodemographic factors, medical history, and cardiovascular risk factors. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: We found disparities in MVPA in AYA cancer survivors by sociodemographic, medical, and cardiovascular risk factors. Understanding trajectories of MVPA among different sociodemographic populations is needed to identify opportunities for intervention.

Cardiometabolic healthcare for men with prostate cancer: an MD Anderson Cancer Center experience.

BACKGROUND: Men diagnosed with prostate cancer are at risk for competing morbidity and mortality due to cardiometabolic disease given their advanced age at diagnosis, high prevalence of pre-existing risk factors, and receipt of systemic therapy that targets the androgen receptor (AR). Expert panels have stressed the importance of cardiometabolic risk assessment in the clinic and proposed evaluating key risks using consensus paradigms. Yet, there is a gap in real-world evidence for implementation of comprehensive cardiometabolic care for men with prostate cancer. METHODS: This is a retrospective, descriptive study of patients with prostate cancer who were referred and evaluated in the Healthy Heart Program at MD Anderson Cancer Center, which was established to mitigate cardiometabolic risks in men with prostate cancer. Patients were seen by a cardiologist and exercise physiologist to evaluate and manage cardiometabolic risk factors, including blood pressure, cholesterol, blood glucose, tobacco use, and coronary artery disease, concurrent with management of their cancer by a medical oncologist. RESULTS: From December 2018 through October 2021, the Healthy Heart Program enrolled 55 men with prostate cancer, out of which 35 had biochemical, locoregional recurrence or distant metastases, while all received at least a single dose of a luteinizing hormone-releasing hormone (LHRH) analog. Ninety-three percent of men were overweight or obese, and 51% had an intermediate or high risk of atherosclerotic cardiovascular disease at 10 years based on the pooled cohort equation. Most men had an overlap of two or more cardiometabolic diseases (84%), and 25% had an overlap of at least 4 cardiometabolic diseases. Although uncontrolled hypertension and hyperlipidemia were common among the cohort (45% and 26%, respectively), only 29% of men followed up with the clinic. CONCLUSIONS: Men with prostate cancer have a high burden of concurrent cardiometabolic risk factors. At a tertiary cancer center, the Healthy Heart Program was implemented to address this need, yet the utility of the program was limited by poor follow-up possibly due to outside cardiometabolic care and inconvenient appointment logistics, a lack of cardiometabolic labs at the time of visits, and telemedicine visits.

Poor Sit-to-Stand Performance in Adolescent and Young Adult Patients with Sarcoma.

Background: Adolescents and young adult (AYA) patients with sarcoma are at heightened risk of reduced physical capacity and disease-related weakness. Sit-to-stand (STS) performance correlates with lower extremity functionality and activities of daily living; however, little is known regarding the relationship between muscular status and STS performance in patients with sarcoma. This study assessed STS performance in patients with sarcoma and the association between STS performance and the skeletal muscle index (SMI) and skeletal muscle density (SMD). Methods: This study included 30 patients with sarcoma (15-39 years old) treated with high-dose doxorubicin. Patients performed the five-times-STS test before starting treatment and 1 year after the baseline test. STS performance was correlated with SMI and SMD. SMI and SMD were quantified using computed tomography scans taken at the level of the 4th thoracic vertebra (T4). Results: Mean performance on the STS test at baseline and 1 year was 2.2-fold and 1.8-fold slower than the age-matched general population, respectively. A lower SMI was associated with worse performance on the STS test (p = 0.01). Similarly, lower SMD at baseline was also associated with poorer STS performance (p < 0.01). Conclusion: Patients with sarcoma have very poor STS performance at baseline and 1 year, which was accompanied by low SMI and SMD at T4.The inability for AYAs to return to healthy age normative STS standards by 1 year may indicate a need for early interventions to enhance skeletal muscle recovery and promote physical activity during and after treatment.

Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy.

BACKGROUND: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status. METHODS: Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting. RESULTS: Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (p < 0.01 & p = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross-sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all p < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (p < 0.01). CONCLUSION: Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.

Circulating microRNAs and Cytokines as Prognostic Biomarkers for Doxorubicin-Induced Cardiac Injury and for Evaluating the Effectiveness of an Exercise Intervention.

PURPOSE: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions. EXPERIMENTAL DESIGN: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated patients with sarcoma were also evaluated before and 24 hours after therapy. RESULTS: Elevations in plasma miRNA-1, miRNA-499 and IL1α, IL1ß, and IL6 were seen in DOX-treated mice with decreased ejection fraction and fractional shortening 24 hours after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during DOX, there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 patients with sarcoma treated with DOX. CONCLUSIONS: These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Sedentary Behavior and Physical Functioning in Middle-Age and Older Adults Living in the United States: The Reasons for Geographic and Racial Differences in Stroke Study.

PURPOSE: Sedentary behavior is associated with poor physical function in older adults, which can lead to accelerated skeletal muscle aging (sarcopenia) and premature mortality. We examined the independent and joint effects of sedentary behavior and moderate to vigorous intensity physical activity (MVPA) with measures of physical functioning. METHODS: We studied 5408 participants in the REasons for Geographic and Racial Differences in Stroke study who wore a hip-mounted accelerometer over seven consecutive days (2009-2013) and had self-reported and directly observed physical function (time walk, chair stand test) measured during an in-home visit conducted from 2013 to 2016. RESULTS: Greater sedentary time was significantly associated with poorer chair stand and timed walk scores. Substituting 30 min of sedentary time with 30 min of MVPA was associated with significant improvements in chair stands (ß -0.57; P = 0.007) and timed walk (ß -0.36; P = 0.01). Similar, but less robust, findings were observed for reallocations of sedentary time to light-intensity physical activity. In joint association analyses, high sedentary time in combination with low MVPA (but not in combination with high MVPA) was associated with poorer physical function compared with the referent group (low sedentary time/high MVPA; P < 0.001 for all). CONCLUSIONS: Greater time spent being sedentary was associated with worse physical functioning outcomes. However, reallocations of sedentary time to light-intensity physical activity, and especially MVPA, were associated with more favorable physical functioning. Interventions aimed to increase MVPA and reduce sedentary behavior should be a priority, especially among populations at greatest risk for sarcopenia and physical function decline.

Short-Term Changes in Skeletal Muscle Mass After Anthracycline Administration in Adolescent and Young Adult Sarcoma Patients.

Identification of anthracycline-induced muscle loss is critical for maintaining health in adolescent and young adult (AYA) cancer patients. We used routine chest computed tomography (CT) scans to investigate changes in skeletal muscle of 16 AYA sarcoma patients at thoracic vertebrae 4 (T4) after anthracycline treatment. CT images were examined at three time points (prechemotherapy, postchemotherapy, and 1 year). Significant changes in total skeletal muscle index and density were seen after chemotherapy (p = 0.021 and p = 0.016, respectively) and at 1 year versus baseline (both p < 0.05). This study supports the use of T4 as an early indicator of skeletal muscle loss in AYAs.