Exercise effects on arterial stiffness and heart health in children with excess weight: The SMART RCT.

INTRODUCTION: Childhood obesity and inactivity are associated with cardiovascular risk. Evidence is limited for exercise effects on arterial health in children. METHODS: One hundred and seventy-five inactive children with overweight or obesity (8-11 years, ≥85th percentile BMI, 61% female, 87% Black, 73% with obesity) were randomized to an 8-month daily after-school aerobic exercise program (40 min/day, n = 90) or a sedentary control condition (n = 85). Carotid-femoral pulse wave velocity (PWV, primary outcome, arterial stiffness), fitness, adiposity, blood pressure (BP), glucose, insulin resistance, lipids, and C-reactive protein were measured at baseline and posttest (8 months). Adiposity, fitness, and BP were measured again at follow-up, 8-12 months later. Intent-to-treat analyses were conducted using mixed models. RESULTS: The study had 89% retention, with attendance of 59% in exercise and 64% in the control condition, and vigorous exercise participation (average heart rate 161 ± 7 beats/min). Compared with controls, the exercise group had twice the improvement in fitness (VÈ®2 peak, 2.7 (95% CI 1.8, 3.6) vs. 1.3 (0.4, 2.3) mL/kg/min) and adiposity (-1.8 (-2.4, -1.1) vs. -0.8 (-1.5, -0.1)%), each p = 0.04, and a large improvement in HDL-cholesterol (0.13 (0.075, 0.186) vs. -0.028 (-0.083, 0.023) mmol/L, p < 0.0001). There was no group × time effect on other outcomes at 8 months, or on any outcomes at follow-up. The change in PWV at 8 months correlated with changes in insulin and insulin resistance (both r = 0.32), diastolic BP (r = 0.24), BMI (r = 0.22), and adiposity (r = 0.18). CONCLUSIONS: Eight months of aerobic exercise training improved fitness, adiposity, and HDL-cholesterol levels, but did not reduce arterial stiffness in children with excess weight. PWV improved as a function of insulin resistance, BP, BMI, and adiposity. Weight loss may be required to improve arterial stiffness. Exercise benefits waned after discontinuing the program.

Phylloquinone Intake Is Associated with Cardiac Structure and Function in Adolescents.

BACKGROUND: Associations between childhood vitamin K consumption and cardiac structure and function have not been investigated. OBJECTIVE: We determined associations between phylloquinone (vitamin K-1) intake and left ventricular (LV) structure and function in adolescents. METHODS: We assessed diet with three to seven 24-h recalls and physical activity (PA) by accelerometry in 766 adolescents (aged 14-18 y, 50% female, 49% black). Fat-free soft tissue (FFST) mass and fat mass were measured by dual-energy X-ray absorptiometry. LV structure [LV mass (g)/height (m)2.7 (LV mass index) and relative wall thickness] and function [midwall fractional shortening (MFS) and ejection fraction] were assessed by echocardiography. Associations were evaluated by comparing the LV structure and function variables across tertiles of phylloquinone intake. Prevalence and OR of LV hypertrophy (LV mass index >95th percentile for age and sex) were also assessed by phylloquinone tertiles. RESULTS: The prevalence of LV hypertrophy progressively decreased across tertiles of phylloquinone intake (P-trend < 0.01). Multinomial logistic regression-adjusting for age, sex, race, Tanner stage, systolic blood pressure, FFST mass, fat mass, socioeconomic status, PA, and intakes of energy, fiber, calcium, vitamin C, vitamin D, and sodium-revealed that compared with the highest phylloquinone intake tertile (reference group), the adjusted OR for LV hypertrophy was 3.3 (95% CI: 1.2, 7.4) for those in the lowest phylloquinone intake tertile. When LV structure variables were compared across phylloquinone intake tertiles adjusting for the same covariates, there were significant linear downward trends for LV mass index (6.5% difference, tertile 1 compared with tertile 3) and relative wall thickness (9.2% difference, tertile 1 compared with tertile 3; both P-trend ≤ 0.02). Conversely, significant linear upward trends across phylloquinone intake tertiles were observed for MFS (3.4% difference, tertile 1 compared with tertile 3) and ejection fraction (2.6% difference, tertile 1 compared with tertile 3; both P-trend < 0.04). CONCLUSION: Our adolescent data suggest that subclinical cardiac structure and function variables are most favorable at higher phylloquinone intakes.

Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction.

Endothelial cell-selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM-/- ) and also performed uninephrectomy and aldosterone infusion (UNX-Aldo) to induce volume and pressure overload. Using echocardiography, we found that ESAM-/- mice display no change in systolic function. However, they develop LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E = early, A = late mitral inflow peak velocities), increased E/e' ratio, isovolumic relaxation time (IVRT), and E wave deceleration time. An unbiased automated tracing and 3D reconstruction of coronary vasculature revealed that ESAM-/- mice had reduced coronary vascular density. Arteries of ESAM-/- mice exhibited impaired endothelial sprouting and in cultured endothelial cells siRNA-mediated ESAM knockdown reduced tube formation. Changes in ESAM-/- mice were accompanied by elevated myocardial inflammatory cytokine and myeloperoxidase-positive neutrophil levels. Furthermore, UNX-Aldo procedure in wild type mice induced LV diastolic dysfunction, which was accompanied by significantly increased serum ESAM levels. When compared to wild types, ESAM-/- mice with UNX-Aldo displayed worsening of LV diastolic function, as indicated by increased IVRT and pulmonary edema. Thus, we propose that ESAM plays a mechanistic role in proper myocardial vascularization and the maintenance of LV diastolic function under basal and hemodynamic stress conditions.

Sleep Variability, Sleep Irregularity, and Nighttime Blood Pressure Dipping.

BACKGROUND: Circadian rhythm regulates many important biological functions in humans. The goal of this study is to explore the impact of day-to-day deviations in the sleep-wake cycle on nighttime blood pressure (BP) dipping and further examine whether the ethnic difference in day-to-day deviations in sleep patterns can explain the ethnic difference in nighttime BP dipping. METHODS: Twenty-four-hour ambulatory BP monitoring and 7-day accelerometer data were obtained from 365 adult participants (age range, 18.7-50.1 years; 52.6% Black participants and 47.3% European Americans; 64.1% females). Systolic BP dipping level was used to represent nighttime BP dipping. The SD of sleep duration was calculated as the index of sleep variability, and the SD of sleep midpoint was calculated as the index of sleep irregularity. RESULTS: A 1-hour increase in the SD of sleep midpoint was associated with a 1.16% decrease in nighttime BP dipping (P<0.001). A 1-hour increase in the SD of sleep duration was associated with a 1.39% decrease in nighttime BP dipping (P=0.017). The ethnic difference in the SD of sleep midpoint can explain 29.2% of the ethnicity difference in BP dipping (P=0.008). CONCLUSIONS: Sleep variability and sleep irregularity are associated with blunted BP dipping in the general population. In addition, data from the present investigation also demonstrate that the ethnic difference in sleep irregularity could partly explain the ethnic difference in BP dipping, an important finding that may help reduce the health disparity between Black participants and European Americans.

Characterization of Resting-State Functional Connectivity Changes in Hypertension by a Modified Difference Degree Test.

Introduction: Hypertension affects over a billion people worldwide, and the application of neuroimaging may elucidate changes brought about by the disease. We have applied a graph theory approach to examine the organizational differences in resting-state functional magnetic resonance imaging (rs-fMRI) data between hypertensive and normotensive participants. To detect these groupwise differences, we performed statistical testing using a modified difference degree test (DDT). Methods: Structural and rs-fMRI data were collected from a cohort of 52 total (29 hypertensive and 23 normotensive) participants. Functional connectivity maps were obtained by partial correlation analysis of participant rs-fMRI data. We modified the DDT null generation algorithm and validated the change through different simulation schemes and then applied this modified DDT to our experimental data. Results: Through a comparative analysis, the modified DDT showed higher true positivity rates (TPR) when compared with the base DDT while also maintaining false positivity rates below the nominal value of 5% in nearly all analytically thresholded trials. Applying the modified DDT to our rs-fMRI data showed differential organization in the hypertension group in the regions throughout the brain including the default mode network. These experimental findings agree with previous studies. Conclusions: While our findings agree with previous studies, the experimental results presented require more investigation to prove their link to hypertension. Meanwhile, our modification to the DDT results in higher accuracy and an increased ability to discern groupwise differences in rs-fMRI data. We expect this to be useful in studying groupwise organizational differences in future studies.

Exercise effects on quality of life, mood, and self-worth in overweight children: the SMART randomized controlled trial.

Overweight children are at risk for poor quality of life (QOL), depression, self-worth, and behavior problems. Exercise trials with children have shown improved mood and self-worth. Few studies utilized an attention control condition, QOL outcomes, or a follow-up evaluation after the intervention ends. The purpose is to test effects of an exercise program versus sedentary program on psychological factors in overweight children. One hundred seventy-five overweight children (87% black, 61% female, age 9.7 ± 0.9 years, 73% obese) were randomized to an 8 month aerobic exercise or sedentary after-school program. Depressive symptoms, anger expression, self-worth, and QOL were measured at baseline and post-test. Depressive symptoms and QOL were also measured at follow-up. Intent-to-treat mixed models evaluated intervention effects, including sex differences. At post-test, QOL, depression, and self-worth improved; no group by time or sex by group by time interaction was detected for QOL or self-worth. Boys' depressive symptoms improved more and anger control decreased in the sedentary intervention relative to the exercise intervention at post-test. At follow-up, depressive symptoms in boys in the sedentary group decreased more than other groups. Exercise provided benefits to QOL, depressive symptoms, and self-worth comparable to a sedentary program. Sedentary programs with games and artistic activities, interaction with adults and peers, and behavioral structure may be more beneficial to boys' mood than exercise. Some benefits of exercise in prior studies are probably attributable to program elements such as attention from adults. Trial Registration: Clinicaltrials.gov, NCT02227095.

Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in African American Hemodialysis Patients.

BACKGROUND: Matrix Gla protein (MGP) is a vascular calcification inhibitor dependent upon vitamin K for activation. Evidence suggests that elevated plasma inactive MGP levels (desphospho-uncarboxylated MGP, dp-ucMGP; indicating poorer vascular vitamin K status) are associated with greater cardiovascular disease (CVD) risk. Despite African Americans experiencing highest rates of kidney failure and CVD events, relationships between dp-ucMGP and CVD risk markers have not been examined in this population. We investigated vascular vitamin K status (via plasma dp-ucMGP) between African American hemodialysis (HD) patients and healthy controls, and the associations of dp-ucMGP with arterial stiffness and endothelial function in HD patients only. METHODS: In 37 African American HD patients and 37 age- and race-matched controls, plasma dp-ucMGP was measured by enzyme immunoassay as a marker of vascular vitamin K status. Carotid-femoral pulse wave velocity (PWV; arterial stiffness measurement) and brachial artery flow-mediated dilation (FMD; endothelial function measurement) were assessed by applanation tonometry and ultrasound, respectively, in HD patients only. RESULTS: Mean dp-ucMGP levels were 5.6 times higher in HD patients vs. controls (2,139 ± 1,102 vs. 382 ± 181 pmol/l, P < 0.01). Multiple linear regression, adjusting for age, sex, dialysis vintage, diabetes mellitus, CVD history, body mass index, and blood pressure, revealed that dp-ucMGP was independently related to PWV (standardized ß = 0.49) and FMD (standardized ß = -0.53) (both P < 0.01). CONCLUSIONS: Our data suggest that the higher plasma dp-ucMGP concentrations found in African American HD patients may be associated with greater arterial stiffness and endothelial dysfunction.

Fitness, Sleep-Disordered Breathing, Symptoms of Depression, and Cognition in Inactive Overweight Children: Mediation Models.

OBJECTIVES: We used mediation models to examine the mechanisms underlying the relationships among physical fitness, sleep-disordered breathing (SDB), symptoms of depression, and cognitive functioning. METHODS: We conducted a cross-sectional secondary analysis of the cohorts involved in the 2003-2006 project PLAY (a trial of the effects of aerobic exercise on health and cognition) and the 2008-2011 SMART study (a trial of the effects of exercise on cognition). A total of 397 inactive overweight children aged 7-11 received a fitness test, standardized cognitive test (Cognitive Assessment System, yielding Planning, Attention, Simultaneous, Successive, and Full Scale scores), and depression questionnaire. Parents completed a Pediatric Sleep Questionnaire. We used bootstrapped mediation analyses to test whether SDB mediated the relationship between fitness and depression and whether SDB and depression mediated the relationship between fitness and cognition. RESULTS: Fitness was negatively associated with depression ( B = -0.041; 95% CI, -0.06 to -0.02) and SDB ( B = -0.005; 95% CI, -0.01 to -0.001). SDB was positively associated with depression ( B = 0.99; 95% CI, 0.32 to 1.67) after controlling for fitness. The relationship between fitness and depression was mediated by SDB (indirect effect = -0.005; 95% CI, -0.01 to -0.0004). The relationship between fitness and the attention component of cognition was independently mediated by SDB (indirect effect = 0.058; 95% CI, 0.004 to 0.13) and depression (indirect effect = -0.071; 95% CI, -0.01 to -0.17). CONCLUSIONS: SDB mediates the relationship between fitness and depression, and SDB and depression separately mediate the relationship between fitness and the attention component of cognition.

Physical Activity Interventions for Neurocognitive and Academic Performance in Overweight and Obese Youth: A Systematic Review.

This article examines cognitive, academic, and brain outcomes of physical activity in overweight or obese youth, with attention to minority youth who experience health disparities. Physically active academic lessons may have greater immediate cognitive and academic benefits among overweight and obese children than normal-weight children. Quasi-experimental studies testing physical activity programs in overweight and obese youth show promise; a few randomized controlled trials including African Americans show efficacy. Thus, making academic lessons physically active may improve inhibition and attentiveness, particularly in overweight youngsters. Regular physical activity may be efficacious for improving neurologic, cognitive, and achievement outcomes in overweight or obese youth.

Passive Smoke Exposure and Its Effects on Cognition, Sleep, and Health Outcomes in Overweight and Obese Children.

BACKGROUND: Passive smoke exposure (PSE) may be a risk factor for childhood overweight and obesity and is associated with worse neurocognitive development, cognition, and sleep in children. The purpose of the study is to examine the effects of PSE on adiposity, cognition, and sleep in overweight and obese children using an objective measure of PSE. METHODS: Overweight or obese children (n = 222) aged 7-11 (9.4 ± 1.1 years; 58% black; 58% female; 85% obese) were recruited from schools near Augusta, Georgia, over the course of the school year from 2003-2006 for a clinical trial, with data analyzed in 2009-2010. Passive smoke exposure was measured with plasma cotinine. Health, cognitive, and sleep measures and parent report of smoke exposure were obtained. RESULTS: Overweight and obese children with PSE had greater overall and central adiposity than nonexposed overweight and obese children (p < 0.03). However, PSE was unrelated to prediabetes, insulin resistance, or visceral fat. PSE was linked to poorer cognitive scores (p < 0.04) independent of adiposity, but was not related to sleep-disordered breathing. CONCLUSIONS: PSE is associated with fatness and poorer cognition in children. Tailored interventions that target multiple health risk factors including nutrition, physical activity, and tobacco use in children and families are needed to prevent adverse health outcomes related to tobacco use and obesity.

Antisaccade-related brain activation in children with attention-deficit/hyperactivity disorder--A pilot study.

While antisaccade paradigms invoke circuitry associated with cognitive control and attention-deficit/hyperactivity disorder (ADHD), there is a dearth of functional magnetic resonance imaging (fMRI) investigations using antisaccade tasks among children with ADHD. Neural correlates associated with antisaccade performance were examined with fMRI in 11 children with ADHD (10 medicated) matched to 11 typically developing children. Significantly greater brain activation in regions in right dorsolateral prefrontal cortex and caudate nucleus was observed in children with ADHD relative to the control group. This pattern separated the children into their respective groups in a taxonomic manner. Sensitivity analyses probing comorbidity and medication-specific effects showed that results were consistent; however, the caudate nucleus difference was only detectable in the full sample, or in subsets with a more relaxed cluster threshold. Antisaccade performance did not significantly differ between the groups, perhaps as a result of greater brain activation or medication effects in the ADHD group. Thus, antisaccade paradigms may have sensitivity and specificity for the investigation of cognitive control deficits and associated neural correlates in ADHD, and may contribute towards the development of new treatment approaches for children with the disorder.