Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity.

BACKGROUND: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood. OBJECTIVES: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression. METHODS: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygAC). CVD events were ascertained from electronic health records. RESULTS: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygAC (standardized ß: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygAC reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023). CONCLUSIONS: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression.

Diagnostic evaluation and cardiopulmonary exercise test findings in young athletes with persistent symptoms following COVID-19.

OBJECTIVES: Persistent or late-onset cardiopulmonary symptoms following COVID-19 may occur in athletes despite a benign initial course. We examined the yield of cardiac evaluation, including cardiopulmonary exercise testing (CPET), in athletes with cardiopulmonary symptoms after COVID-19, compared CPETs in these athletes and those without COVID-19 and evaluated longitudinal changes in CPET with improvement in symptoms. METHODS: This prospective cohort study evaluated young (18-35 years old) athletes referred for cardiopulmonary symptoms that were present>28 days from COVID-19 diagnosis. CPET findings in post-COVID athletes were compared with a matched reference group of healthy athletes without COVID-19. Post-COVID athletes underwent repeat CPET between 3 and 6 months after initial evaluation. RESULTS: Twenty-one consecutive post-COVID athletes with cardiopulmonary symptoms (21.9±3.9 years old, 43% female) were evaluated 3.0±2.1 months after diagnosis. No athlete had active inflammatory heart disease. CPET reproduced presenting symptoms in 86%. Compared with reference athletes (n=42), there was similar peak VO2 but a higher prevalence of abnormal spirometry (42%) and low breathing reserve (42%). Thirteen athletes (62%) completed longitudinal follow-up (4.8±1.9 months). The majority (69%) had reduction in cardiopulmonary symptoms, accompanied by improvement in peak VO2 and oxygen pulse, and reduction in resting and peak heart rate (all p<0.05). CONCLUSION: Despite a high burden of cardiopulmonary symptoms after COVID-19, no athlete had active inflammatory heart disease. CPET was clinically useful to reproduce symptoms with either normal testing or identification of abnormal spirometry as a potential therapeutic target. Improvement in post-COVID symptoms was accompanied by improvements in CPET parameters.

Priming cardiac function with voluntary respiratory maneuvers and effect on early exercise oxygen uptake.

Oxygen uptake (V̇o2) at exercise onset is determined in part by acceleration of pulmonary blood flow ([Formula: see text]). Impairments in the [Formula: see text] response can decrease exercise tolerance. Prior research has shown that voluntary respiratory maneuvers can augment venous return, but the corollary impacts on cardiac function, [Formula: see text] and early-exercise V̇o2 remain uncertain. We examined 1) the cardiovascular effects of three distinct respiratory maneuvers (abdominal, AB; rib cage, RC; and deep breathing, DB) under resting conditions in healthy subjects (Protocol 1, n = 13), and 2) the impact of pre-exercise DB on pulmonary O2 transfer during initiation of moderate-intensity exercise (Protocol 2, n = 8). In Protocol 1, echocardiographic analysis showed increased right ventricular (RV) cardiac output and left ventricular (LV) cardiac output (RVCO and LVCO, respectively), following AB (by +23 ± 13 and +18 ± 15%, respectively, P < 0.05), RC (+23 ± 16; +14 ± 15%, P < 0.05), and DB (+27 ± 21; +23 ± 14%, P < 0.05). In Protocol 2, DB performed for 12 breaths produced a pre-exercise increase in V̇o2 (+801 ± 254 mL·min-1 over ∼6 s), presumably from increased [Formula: see text], followed by a reduction in pulmonary O2 transfer during early phase exercise (first 20 s) compared with the control condition (149 ± 51 vs. 233 ± 65 mL, P < 0.05). We conclude that 1) respiratory maneuvers enhance RVCO and LVCO in healthy subjects under resting conditions, 2) AB, RC, and DB have similar effects on RVCO and LVCO, and 3) DB can increase [Formula: see text] before exercise onset. These findings suggest that pre-exercise respiratory maneuvers may represent a promising strategy to prime V̇o2 kinetics and thereby to potentially improve exercise tolerance in patients with impaired cardiac function.NEW & NOTEWORTHY We demonstrate that different breathing maneuvers can augment both right and left-sided cardiac output in healthy subjects. These maneuvers, when performed immediately before exercise, result in a pre-exercise "cardiodynamic" increase in oxygen uptake (V̇o2) associated with a subsequent reduction in the "cardiodynamic" V̇o2 normally seen during early exercise. We conclude that pre-exercise breathing maneuvers are a plausible tool worthy of additional study to prime V̇o2 kinetics and improve exercise tolerance in patients with cardiovascular disease.

Impact of the COVID-19 pandemic on perceived cardiorespiratory fitness in athlete patients.

INTRODUCTION: Cardiorespiratory fitness (CRF), as one of the most potent prognostic factors in medicine, is followed longitudinally to guide clinical management. Coronavirus disease 2019 (COVID-19) pandemic-related changes in lifestyle stand to influence CRF. OBJECTIVE: To assess the influence of the pandemic on perceived CRF in athlete patients and evaluate how perceived CRF change was related to demographics, pre-pandemic measured CRF, and current physical activity (PA). DESIGN: Prospective cohort study, utilizing electronic survey. SETTING: Tertiary care sports cardiology clinical practice. PARTICIPANTS: Adult athlete patients without COVID-19 with pre-pandemic measured CRF using cardiopulmonary exercise testing. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Perceived change in CRF since pandemic onset; association between perceived CRF change and demographics, PA, health status, and pre-pandemic measured CRF assessed via analysis of variance (ANOVA). RESULTS: Among 62 participants (male: 71%, 50.1 ± 12.1 years old), 40% (25/62) reported no change and 32% (20/62) reported an increase in perceived CRF since pandemic onset. Among the 27% (17/62) who reported a decrease in perceived CRF, in most (12/17), this was characterized as only mild. Demographics and pre-pandemic measured CRF did not differ across groups of perceived CRF change. Participants with a moderate or greater decrease in perceived CRF regarded their overall health (via Euro Quality of Life Visual Analogue Scale) as worse than other groups (ANOVA, p = .001). Although total PA was similar across groups, those who had improvement in perceived CRF reported higher levels of moderate intensity PA (ANOVA, p = .008). CONCLUSIONS: The majority of participants perceived that they had maintained or improved CRF over the pandemic. Findings from this study suggest that a reduction in perceived CRF from pre-pandemic values in athletic patients in clinical practice may not result from population-wide pandemic changes in lifestyle. Worse health status and lower levels of moderate intensity PA were associated with perceived reduction in CRF over the pandemic in athlete patients.

Healthspan and chronic disease burden among young adult and middle-aged male former American-style professional football players.

OBJECTIVE: To examine the relationships between age, healthspan and chronic illness among former professional American-style football (ASF) players. METHODS: We compared age-specific race-standardised and body mass index-standardised prevalence ratios of arthritis, dementia/Alzheimer's disease, hypertension and diabetes among early adult and middle-aged (range 25-59 years) male former professional ASF players (n=2864) with a comparator cohort from the National Health and Nutrition Examination Survey and National Health Interview Survey, two representative samples of the US general population. Age was stratified into 25-29, 30-39, 40-49 and 50-59 years. RESULTS: Arthritis and dementia/Alzheimer's disease were more prevalent among ASF players across all study age ranges (all p<0.001). In contrast, hypertension and diabetes were more prevalent among ASF players in the youngest age stratum only (p<0.001 and p<0.01, respectively). ASF players were less likely to demonstrate intact healthspan (ie, absence of chronic disease) than the general population across all age ranges. CONCLUSION: These data suggest the emergence of a maladaptive early ageing phenotype among former professional ASF players characterised by premature burden of chronic disease and reduced healthspan. Additional study is needed to investigate these findings and their impact on morbidity and mortality in former ASF players and other athlete groups.

Sex Differences in Circulating Biomarkers of Cardiovascular Disease.

BACKGROUND: Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in cardiovascular disease (CVD). OBJECTIVES: This study sought to investigate sex differences in circulating biomarkers representative of biological pathways implicated in the development of CVD among Framingham Heart Study participants. METHODS: The authors measured 71 circulating CVD protein biomarkers in 7,184 participants (54% women, mean age 49 years). Multivariable models were used to evaluate the associations of sex, menopause, and hormone status with biomarkers. Cox models were used to examine whether sex modified the association of biomarkers with incident CVD. RESULTS: Of 71 biomarkers examined, 61 (86%) differed significantly between men and women, of which 37 were higher in women (including adipokines and inflammatory markers such as leptin and C-reactive protein), and 24 were higher in men (including fibrosis and platelet markers such as MMP-8 (matrix metalloproteinase-8) and TIMP-1 (tissue inhibitor of metalloproteinases 1); false discovery rate q < 0.05 for all). Sex differences in biomarker profiles were most pronounced between pre-menopausal women versus men, with attenuated sex differences among post-menopausal women not taking hormone replacement therapy. Sex modified the association of specific biomarkers with incident CVD, including CD14 and apolipoprotein B (pinteraction <0.05 for all). CONCLUSIONS: In a predominantly Caucasian population, the authors identified widespread sex differences in circulating biomarkers that reflect distinct pathways implicated in CVD, including inflammation, adiposity, fibrosis, and platelet homeostasis. Menopause and hormone status accounted for some, but not all, of the observed sex differences. Further investigation into factors underlying sex-based differences may provide mechanistic insight into CVD development.