Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.

Waist-circumference-to-height-ratio had better longitudinal agreement with DEXA-measured fat mass than BMI in 7237 children.

BACKGROUND: The absolute agreement of surrogate measures of adiposity with dual-energy X-ray absorptiometry (DEXA)-measured body composition was examined. METHODS: Over a 15-year follow-up, 7237 (3667 females) nine-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort were included. Total fat mass (FM) and trunk FM were serially measured with DEXA at ages 9, 11, 15, 17, and 24 years. BMI and waist circumference-to-height ratio (WHtR) were computed. Pearson's correlations, intraclass correlations (ICC), and area under curve (AUC) analyses were conducted. RESULTS: Over 15 years, BMI, total FM, and trunk FM, increased but WHtR was relatively stable. WHtR provided a better longitudinal absolute agreement [males ICC 0.84 (95% CI 0.84-0.85); females 0.81 (0.80-0.82)] than BMI [(males (0.65 (0.64-0.66); females 0.72 (0.71-0.73)] with total FM as well as trunk FM from ages 9-24 years. WHtR cut-point for predicting excess total FM (75th-95th percentile) was 0.50-0.53 in males [AUC 0.86-0.94, sensitivity 0.51-0.79 and specificity 0.93-0.95]. WHtR cut-point for predicting excess total FM (75th-95th percentile) was 0.52-0.54 in females [AUC 0.83-0.95, sensitivity 0.38-0.68 and specificity 0.92-0.95]. Results were similar with trunk FM. CONCLUSION: WHtR is an inexpensive alternative to BMI for predicting FM in pediatrics. IMPACT: Waist circumference-to-height ratio (WHtR) is a better adiposity surrogate measure than body mass index (BMI) in predicting fat mass and discriminating lean mass from childhood through young adulthood. BMI has been used as an inexpensive surrogate measure of adiposity in children for several decades. However, emerging findings suggest that BMI fails to discriminate between fat mass adiposity and lean mass. This is the first-ever longitudinal study in over 7000 children followed up for 15 years that identified WHtR as an inexpensive accurate measure that discriminates fat mass from lean mass that could replace BMI measure of obesity in pediatrics.

Cumulative insulin resistance and hyperglycemia with arterial stiffness and carotid IMT progression in 1,779 adolescents: a 9-yr longitudinal cohort study.

In pediatric population with diabetes and obesity, insulin resistance (HOMA-IR) has been associated with worsening vascular outcomes, however, the cumulative role of HOMA-IR, hyperglycemia, and hyperinsulinemia on repeatedly measured vascular outcomes in asymptomatic youth is unknown. We examined the longitudinal associations of fasting glucose, insulin, and HOMA-IR with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). From the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, UK 1,779, 15-yr-old participants were followed up for 9 yr. Glucose, insulin, and HOMA-IR assessed at 15, 17, and 24 yr and sex-specifically dichotomized as ≥75th percentile, indicating high category and <75th percentile as reference. cfPWV and cIMT were measured at ages 17 and 24 yr. Associations were examined using linear mixed-effect models adjusted for cardiometabolic and lifestyle covariates. Among 1,779 participants [49.9% female], glucose, insulin, and HOMA-IR had a J- or U-shaped increase from ages 15 through 24 yr. The cumulative exposures to hyperinsulinemia effect estimate -0.019 mU/L; [95% CI -0.019 to -0.002; P = 0.033] and high HOMA-IR: -0.021; [-0.039 to -0.004; P = 0.019] from 15 to 24 yr of age were negatively associated with the 7-yr cfPWV progression. Only cumulative hyperinsulinemia and high HOMA-IR from ages 15 to 17 yr but not from ages 17 to 24 yr was associated with decreased cfPWV progression. There were no associations between cumulative hyperglycemia and cfPWV or cIMT progression. Hyperinsulinemia and HOMA-IR were not associated with cIMT progression. In conclusion, late adolescence may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.NEW & NOTEWORTHY Fasting plasma glucose, insulin, and insulin resistance had a J- or U-shaped increase from 15 to 24 yr with the base of the curve at age 17 yr. Cumulative high insulin and high insulin resistance from 15 to 24 yr were negatively associated with arterial stiffness progression from ages 17 to 24 yr. Age 17 yr may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.

Arterial stiffness preceding metabolic syndrome in 3,862 adolescents: a mediation and temporal causal longitudinal birth cohort study.

The temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, with the risk of incident metabolic syndrome, were examined in youth. A total of 3,862 adolescents, aged 17.7 yr and followed up for 7 yr, from the Avon Longitudinal Study of Parents and Children were included. cfPWV was assessed by Vicorder at baseline and follow up. Metabolic syndrome was determined by the presence of three or more of dual-energy X-ray absorptiometry-measured trunk fat obesity; decreased high-density lipoprotein cholesterol, elevated triglyceride, hyperglycemia, and elevated/hypertensive blood pressure at both measurement time points. Analyses were conducted using generalized logit mixed-effect models and autoregressive cross-lagged and mediation structural equation models. Among 3,862 adolescents [2,143 (55.5%) female], 5% of male and 1.1% of female participants had metabolic syndrome at baseline, whereas 8.8% of male and 2.4% of female participants had metabolic syndrome at follow-up. In the mixed-model analysis, a 7-yr progressive increase in cfPWV was associated with a cumulatively increased risk of incident metabolic syndrome from baseline through follow-up in the total cohort (odds ratio 1.04 [confidence interval, 1.02-1.06], P = 0.002) and in males (1.09 [1.06-1.12], P < 0.001) but not in females (1.01 [0.95-1.06], P = 0.885). In the cross-lagged model, higher cfPWV at baseline was associated with a higher metabolic syndrome score (ß = 0.08, standard error = 0.39, P < 0.0001) at follow-up but metabolic syndrome score at baseline was not associated with cfPWV at follow-up. Cumulatively increased fasting insulin and low-density lipoprotein cholesterol had 12.4 and 9.4% respective mediation effects on the positive relationships between cumulative arterial stiffness and metabolic syndrome score. In conclusion, arterial stiffness temporally preceded incident and progressive metabolic syndrome in youth in a potential causal path, but experimental studies are warranted.NEW & NOTEWORTHY Participants at risk of metabolic syndrome increased twofold during growth from late adolescence to young adulthood. The cumulative increase in arterial stiffness independently predicted the progressive risk of incident metabolic syndrome. Arterial stiffness temporally preceded metabolic syndrome. Increased fasting insulin and low-density lipoprotein cholesterol partly mediated the direct associations between arterial stiffness and metabolic syndrome. Age 17 yr may be an optimal arterial stiffness intervention timing for attenuating metabolic syndrome risks.

Longitudinal left ventricular mass indexing for DEXA-measured lean mass and fat mass: novel normative reference centiles in postpubertal adolescents and young adults.

Left ventricular (LV) hypertrophy derived from LV mass (LVM) cut point is a marker of cardiovascular events in adults and target organ damage in pediatric research. Inadequate LVM indexing for body size due to scarcity of dual-energy X-ray absorptiometry (DEXA)-measured lean mass may lead to misclassification in the pediatric population. The only LVM indexed for DEXA-measured lean mass reference in children, mean age 11.6 yr, is 3-decades old and accurate LVM indexing in postpubertal adolescents and young adults is nonexistent. We generate new sex-specific LVM indexed for lean mass percentiles in healthy adolescence and young adulthood and correlated them with surrogates for normalizing body size. From the Avon Longitudinal Study of Parents and Children UK birth cohort, 868 adolescents (531 females) aged 17 yr were followed up for 7 yr. Lean mass was measured by DEXA at both time points. Echocardiography M-mode, two-dimensional (2-D), and three-dimensional (3-D) echo data for estimating LVM were collected at baseline and follow-up. Over 7 years, LVM increased in males (177.1 g) and females (133.5 g) at 17 yr to 199.9 g (males) and 145 g (females) at 24 yr. LVM/height3 and LVM/height2.7 provided the most consistent cross-sectional and longitudinal intraclass correlation coefficients with LVM/lean mass in both sexes (0.90-0.93). Indexing LVM by lean mass eliminated the sex difference only at age 24 yr but not at 17 yr. LVM/height2.7 85th percentiles for males and females at age 17 yr were 45.1 g/m2.7 and 41.4 g/m2.7, respectively, and at age 24 yr the 75th percentiles were 45.5 g/m2.7 and 41.7 g/m2.7, respectively. The 95th percentiles for males and females at age 17 yr were 49.5 g/m2.7 and 46.8 g/m2.7, respectively, and at age 24 yr were 57.1 g/m2.7 and 50.2 g/m2.7, respectively. These new reference percentile cut points were higher than the currently used 95th percentile pediatric reference of 38.6 g/m2.7. Future studies are warranted in youth with clinical diseases to examine whether these new cut points provide a more accurate stratification of cardiovascular risk.NEW & NOTEWORTHY Current left ventricular mass cut points for pediatric left ventricular hypertrophy are inaccurate. The inaccuracies are due, in part, to the average age of participants (11.6 yr) evaluated and also due to the lack of Echo and DEXA-measured body composition in postpubertal youth. Novel sex-based cut points are proposed for postpubertal youths at 17 and 24 yr. The new 95th percentile cut points are 15-20 g/m2.7 higher than the current cut point.

Does arterial stiffness mediate or suppress the associations of blood pressure with cardiac structure and function in adolescents?

There is limited understanding of the role of arterial stiffness in cardiovascular disease risk in the pediatric population, lagging behind strong evidence in the adult population. Arterial stiffness progression among adolescents with hypertension has been considered hypertension-mediated vascular damage. However, emerging pediatric reports suggest that arterial stiffness may precede increased blood pressure and hypertension, whereas increased blood pressure from childhood has been associated with signs of cardiac damage in mid-adulthood. Thus, this study used a third variable analytical approach to examine whether arterial stiffness mediates or suppresses the effects of increasing blood pressure on cardiac structure and function in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of 1,778 adolescents. After an adjustment for cardiometabolic and lifestyle factors, arterial stiffness measured as carotid-femoral pulse wave velocity partly suppressed the association of higher systolic blood pressure with higher left ventricular mass (standardized regression coefficient, ß = -0.012; P = 0.017; suppression effect = 4%), partly mediated the associations of higher systolic and diastolic blood pressure with higher relative ventricular wall thickness, and partly suppressed the association of higher diastolic blood pressure with lower left ventricular diastolic function (ß = -0.021; P = 0.003; suppression effect = 14.5%). In conclusion, increasing arterial stiffness could attenuate some of the adverse effects of increased blood pressure on cardiac structure and function in adolescents possibly by modifying the Windkessel effects.NEW & NOTEWORTHY The present study demonstrates that the associations of blood pressure with cardiac function and structure in adolescents may be mediated or suppressed by arterial stiffness depending on the blood pressure phenotype: systolic or diastolic. Arterial stiffness may be considered as an intermediate pathway to attenuate the effect of increased blood pressure on altered cardiac structure and function in youth.

Elevated Blood Pressure and Worsening Cardiac Damage During Adolescence.

OBJECTIVES: To examine the longitudinal course for the development of elevated blood pressure (BP)/hypertension and cardiac damage in adolescents. STUDY DESIGN: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 (1011 female) 17-year-old adolescents were followed up for 7 years. BP and echocardiography were assessed at ages 17 and 24 years. Elevated/hypertensive BP was defined as ≥130 mm Hg systolic and ≥85 mm Hg diastolic. Left ventricular (LV) mass indexed for height2.7 (LVMI2.7) ≥51 g/m2.7 was defined as LV hypertrophy (LVH) and LV diastolic function (LVDF) E/A <1.5 as LVD dysfunction (LVDD). Data were analyzed with generalized logit mixed-effect models and cross-lagged structural equation temporal path models adjusting for cardiometabolic and lifestyle factors. RESULTS: Over follow-up, the prevalence of elevated systolic BP/hypertension increased from 6.4% to 12.2%, LVH from 3.6% to 7.2%, and LVDD from 11.1% to 16.3%. Cumulative elevated systolic BP/hypertension was associated with worsening LVH in female participants (OR 1.61, CI 1.43-1.80 P < .001) but not in male participants. Elevated systolic BP/hypertension was associated with worsening LVDD in male and female participants. Elevated diastolic BP/hypertension was associated with worsening LVH in male and female participants. In cross-lagged temporal path models, higher baseline systolic BP was associated with LVDF (ß = 0.09, SE = 0.002, P = .029) but not LVMI2.7 at follow-up. Higher baseline cardiac indices were not associated with follow-up systolic BP. Higher baseline diastolic BP was associated with follow-up higher cardiac indices except LVDF. Baseline LVMI2.7 was not associated with follow-up diastolic BP. CONCLUSIONS: Elevated BP/hypertension may temporally precede premature cardiac damage in youth.

Associations of accelerometer-based sedentary time, light physical activity and moderate-to-vigorous physical activity with resting cardiac structure and function in adolescents according to sex, fat mass, lean mass, BMI, and hypertensive status.

BACKGROUND: This study examined the independent relationships of device-based measured sedentary time (ST) and physical activity (PA) in relation to cardiac structural and functional geometry among adolescents. METHODS: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 530 (50% female) adolescents aged 17 years had complete ST, PA, cardiac, and covariate measures. Echocardiography cardiac measures were left ventricular mass indexed for height2.7 (LVMI2.7 ), relative wall thickness, LV diastolic function (LVDF), and LV filling pressure (LVFP). Overweight/obesity and elevated systolic/BP hypertension were categorized as body mass index >24.99 kg/m2 and ≥130 mmHg, respectively. Data were analyzed with linear regression models adjusting for cardiometabolic factors and lifestyle factors. RESULTS: The prevalence of overweight/obesity in males and females was 17.9% and 24.5%, respectively. The prevalence of elevated systolic BP/hypertension was 11.6% in males and 1.1% among females. The average ST was 484 ± 78 min/day, light PA was 274 ± 62 min/day, and moderate-to-vigorous PA (MVPA) was 41 ± 24 min/day, among females. Average ST, LPA, and MVPA were 468 ± 87 min/day, 293 ± 70 min/day, and 56 ± 30 min/day, respectively, among males. Higher ST was associated with higher LVMI2.7 (standardized ß = 0.16; p = 0.01) among females, but higher ST was associated with lower LVDF in males (ß = -0.14; p = 0.04). Higher ST and MVPA were associated with higher LVMI2.7 in the total cohort, normal weight, and overweight/obese adolescents. Light PA was associated with higher LVDF in the total cohort and normotensives and lower LVFP among adolescents with high lean mass. CONCLUSIONS: Higher ST and MVPA were associated with higher LVMI; however, ST-associated LVMI increase was threefold higher than MVPA-associated LVMI increase. Higher LPA was associated with better cardiac function. Reducing ST and increasing LPA may attenuate the risk of altered cardiac structure and function in adolescents.

Peak oxygen uptake cut-points to identify children at increased cardiometabolic risk - The PANIC Study.

We aimed to develop cut-points for directly measured peak oxygen uptake ( V ˙ O 2 peak ) to identify boys and girls at increased cardiometabolic risk using different scaling methods to control for body size and composition. Altogether 352 children (186 boys, 166 girls) aged 9-11 years were included in the analyses. We measured V̇O2peak directly during a maximal cycle ergometer exercise test and lean body mass (LM) by bioelectrical impedance. We computed a sex- and age-specific cardiometabolic risk score (CRS) by summing important cardiometabolic risk factors and defined increased cardiometabolic risk as >1 standard deviation above the mean of CRS. Receiver operating characteristics curves were used to detect V̇O2peak cut-points for increased cardiometabolic risk. Boys with V̇O2peak <45.8 mL kg body mass (BM)-1  min-1 (95% confidence interval [CI] = 45.1 to 54.6, area under the curve [AUC] = 0.86, P < 0.001) and <63.2 mL kg LM-1  min-1 (95% CI =52.4 to 67.5, AUC = 0.65, P = 0.006) had an increased CRS. Girls with V̇O2peak <44.1 mL kg BM-1  min-1 (95% CI = 44.0 to 58.6, AUC = 0.67, P = 0.013) had an increased CRS. V̇O2peak scaled by BM-0.49 and LM-0.77 derived from log-linear allometric modeling poorly predicted increased cardiometabolic risk in boys and girls. In conclusion, directly measured V ˙ O 2 peak <45.8 mL kg BM-1  min-1 among boys and <44.1 mL kg BM-1  min-1 among girls were cut-points to identify those at increased cardiometabolic risk. Appropriately controlling for body size and composition reduced the ability of cardiorespiratory fitness to identify children at increased cardiometabolic risk.

Associations of Cardiorespiratory Fitness and Adiposity With Arterial Stiffness and Arterial Dilatation Capacity in Response to a Bout of Exercise in Children.

Purpose: To investigate the associations of directly measured peak oxygen uptake ( V˙O2peak ) and body fat percentage (BF%) with arterial stiffness and arterial dilatation capacity in children. Methods: Findings are based on 329 children (177 boys and 152 girls) aged 8-11 years. V˙O2peak was assessed by a maximal cardiopulmonary exercise test on a cycle ergometer and scaled by lean body mass (LM). BF% and LM were measured by bioelectrical impedance. Stiffness index (measure of arterial stiffness) and change in reflection index (ΔRI, measure of arterial dilatation capacity) were assessed by pulse contour analysis. Data were analyzed by linear regression models. Results:V˙O2peak/LM was positively associated with ΔRI in boys adjusted for age and BF% (ß = 0.169, P = .03). Further adjustments for systolic blood pressure, heart rate, and the study group had no effect on this association, but additional adjustment for clinical puberty attenuated it (ß = 0.171, P = .07). BF% was inversely related to ΔRI in boys adjusted for age and V˙O2peak/LM (ß = -0.171, P = .03). V˙O2peak or BF% was not associated with ΔRI in girls or with stiffness index in either boys or girls. Conclusion: Increasing cardiorespiratory fitness and decreasing adiposity may improve arterial health in childhood, especially among boys.

Associations of Sedentary Time and Physical Activity From Childhood With Lipids: A 13-Year Mediation and Temporal Study.

CONTEXT: Among children, evidence on long-term longitudinal associations of accelerometer-measured sedentary time, light physical activity (LPA), and moderate to vigorous PA (MVPA) with lipid indices are few. The mediating role of body composition and other metabolic indices in these associations remains unclear and whether poor movement behavior precedes altered lipid levels is unknown. OBJECTIVE: This study examined the associations of sedentary time, LPA, and MVPA from childhood through young adulthood with increased lipids, the mediating role of body composition, and whether temporal interrelations exist. METHODS: Data from 792 children (58% female; mean [SD] age at baseline, 11.7 [0.2] years), drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort, who had at least 2 time-point measures of accelerometer-based sedentary time, LPA, and MVPA during clinic visits at ages 11, 15, and 24 years and complete fasting plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol measured during follow-up visits at ages 15, 17, and 24 years were analyzed. RESULTS: Total fat mass partly mediated the inverse associations of LPA with low-density lipoprotein cholesterol by 13%, triglyceride by 28%, and total cholesterol by 6%. Total fat mass mediated the inverse associations of MVPA with low-density lipoprotein cholesterol by 37% and total cholesterol by 48%, attenuating the effect on total cholesterol to nonsignificance (P = .077). In the temporal path analyses, higher MVPA at age 15 years was associated with lower low-density lipoprotein cholesterol at 24 years (ß = -0.08, SE, 0.01, P = .022) but not vice versa. CONCLUSION: Sedentary time worsens lipid indices, but increased LPA had a 5- to 8-fold total cholesterol-lowering effect and was more resistant to the attenuating effect of fat mass than MVPA.

Accelerometer-based sedentary time and physical activity from childhood through young adulthood with progressive cardiac changes: a 13-year longitudinal study.

AIMS: Longitudinal evidence on the relationship of sedentary time (ST), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) with changes in cardiac structure and function in the paediatric population is scarce. This evidence is clinically important due to the impact ST can have on the long-term prognosis of healthy young population in the lifetime continuum. This prospective observational study examined the relationships of cumulative ST, LPA, and MVPA from childhood with longitudinal changes in cardiac structure and function. METHODS AND RESULTS: This is a secondary analysis from the Avon Longitudinal Study of Parents and Children, UK birth cohort of 1682 children aged 11 years. Participants who had at least one follow-up timepoints accelerometer-measured ST, LPA, and MVPA over a period of 13 years and repeated echocardiography-measured cardiac structure and function at ages 17- and 24-year clinic visit were included. Left ventricular mass indexed for height2.7 (LVMI2.7) and left ventricular (LV) diastolic function from mitral E/A ratio (LVDF) were computed. Among 1682 children (mean [SD] age, 11.75 [0.24] years; 1054 [62.7%] females), the cumulative one-min/day increase in ST from ages 11 to 24 years was associated with progressively increased LVMI2.7 {effect estimate 0.002 g/m2.7 [confidence interval (CI) 0.001-0.003], P < 0.001}, irrespective of sex, obesity, and hypertensive status. Cumulative one-min/day increase in LPA was associated with a decreased LVMI2.7 (-0.005 g/m2.7 [-0.006 to -0.003], P < 0.0001) but an increased LVDF. Cumulative one-minute/day increase in MVPA was associated with progressively increased LVMI2.7 (0.003 g/m2.7 [0.001-0.006], P = 0.015). CONCLUSION: ST contributed +40% to the 7-year increase in cardiac mass, MVPA increased cardiac mass by +5%, but LPA reduced cardiac mass by -49%. Increased ST may have long-term pathologic effects on cardiac structure and function during growth from childhood through young adulthood; however, engaging in LPA may enhance cardiac health in the young population.

The aim of this longitudinal study including 1682 children and adolescents was to examine the effect of sedentary time (ST), light-intensity physical activity (LPA), moderate-to-vigorous-intensity physical activity (MVPA) on changes in cardiac structural and functional properties during growth until young adulthood. Cumulative ST from childhood contributed a maximum of 40% (+1.29 g/m2.7 out of the total 7-year increase in cardiac mass of 3 g/m2.7) during growth from adolescence to young adulthood. Cumulative LPA from childhood was associated with decreased cardiac mass (−0.005 g/m2.7), amounting to a −49% average reduction (−1.49 g/m2.7 out of 3 g/m2.7) in the increase in cardiac mass across the 7-year observation period. Each minute of cumulative MVPA from childhood was associated with a 5% progressively increased cardiac mass, amounting to +0.15 g/m2.7 out of 3 g/m2.7 increase during growth from adolescence to young adulthood.Participation in LPA of at least 3 h/day and decreasing ST was longitudinally associated with healthier cardiac indices in the young population. The contribution of ST to increased cardiac mass is eight times more than the MVPA-associated physiological increase. Hence, progressively increasing childhood sedentariness may independently and pathologically contribute to worsening cardiac structural and functional alterations in the young population. Childhood sedentariness causes an increased body fat, inflammation, blood pressure, lipid levels, arterial stiffness, and subsequently cardiac enlargement, thereby increasing the risk of adverse cardiovascular health consequences in later life.

Mediating effect of fat mass, lean mass, blood pressure and insulin resistance on the associations of accelerometer-based sedentary time and physical activity with arterial stiffness, carotid IMT and carotid elasticity in 1574 adolescents.

This study examined the mediating effect of total body fat mass, lean mass, blood pressure (BP) and insulin resistance on the associations of sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous PA (MVPA) with carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT) and carotid elasticity in 1574 adolescents from the Avon Longitudinal Study of Parents and Children birth cohort, UK. ST, LPA and MVPA were assessed with ActiGraph accelerometer. ST and LPA were sex-categorised in tertiles as low (reference), moderate and high, while MVPA was categorised as <40 min/day (reference), 40-<60 min/day and ≥60 min/day. cfPWV, cIMT and carotid elasticity were measured with Vicorder and ultrasound. Fat mass and lean mass were assessed with dual-energy X-ray absorptiometry and homeostatic model assessment of insulin resistance (HOMA-IR) was computed. Mediation analyses structural equation models and linear mixed-effect models adjusted for cardiometabolic and lifestyle factors were conducted. Among 1574 adolescents [56.2% female; mean (SD) age 15.4 (0.24) years], 41% males and 17% females accumulated ≥60 min/day of MVPA. Higher ST was associated with lower cIMT partly mediated by lean mass. Higher LPA (standardized ß = -0.057; [95% CI -0.101 to -0.013; p = 0.014]) and the highest LPA tertile were associated with lower cfPWV. BP had no significant mediating effect movement behaviour relations with vascular indices. Lean mass partially mediated associations of higher MVPA with higher cIMT (0.012; [0.007-0.002; p = 0.001], 25.5% mediation) and higher carotid elasticity (0.025; [0.014-0.039; p = 0.001], 28.1% mediation). HOMA-IR mediated the associations of higher MVPA with higher carotid elasticity (7.7% mediation). Engaging in ≥60 min/day of MVPA was associated with higher carotid elasticity. In conclusion, higher LPA was associated with lower arterial stiffness, but higher MVPA was associated with thicker carotid wall explained by higher lean mass.

The Interactive Effects of Sedentary Time, Physical Activity, and Fat Mass on Insulin Resistance in the Young Population.

CONTEXT: Recent evidence in 9-year-old children with overweight/obesity followed up for 7 years until late adolescence concluded that increased physical activity (PA) decreased the risk of high fasting glucose, low insulin sensitivity, and secretion. However, whether this effect persists until young adulthood is unknown. OBJECTIVE: This observational study examined the effects of cumulative sedentary time (ST), light PA (LPA), and moderate-to-vigorous (MVPA) on glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) in 11-year-old children followed up for 13 years until young adulthood. METHODS: Altogether 792 children from the Avon Longitudinal Study of Parents and Children, UK who had data on at least two measures of accelerometer-based movement behaviour during ages 11, 15, and 24 years follow-up clinic visits with complete fasting glucose, insulin, and HOMA-IR measures at ages 15, 17, and 24 years were included. ST, LPA, and MVPA were measured with an accelerometer. RESULTS: Cumulative ST from ages 11-24 years was associated with increased odds (odds ratio 1.20 [95% CI 1.00-1.44] p=0.047) and cumulative LPA was associated with the decreased odds of hyperinsulinemia (0.80 [0.66-0.96] p=0.017) among participants with overweight/obesity. Cumulative MVPA was inversely associated with insulin but after accounting for the mediating role of fat mass, MVPA effect on lowering insulin decreased by 58% resulting in statistical non-significance. In the temporal path analyses, among participants with overweight/obesity, higher glucose at age 15 years was associated with lower LPA and MVPA at 24 years. Higher LPA at 15 years was associated with lower insulin and HOMA-IR at 24 years and vice-versa. CONCLUSIONS: Promoting LPA while decreasing body fat mass and ST may be considered crucial intervention targets to attenuate the risk of hyperinsulinemia and insulin resistance from childhood through young adulthood.

Increasing lipids with risk of worsening cardiac damage in 1595 adolescents: A 7-year longitudinal and mediation study.

BACKGROUND AND AIMS: Longitudinal evidence on the associations of changes in lipids level with changes in cardiac structure and function in youth is limited due to few repeated echocardiography measures. This study examined whether changes in lipid levels from adolescence through young adulthood associate with the risk of cardiac damage progression and potential mechanistic pathways. METHODS: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and non-HDL-c measured at 17- and 24-year clinic visit were included. Echocardiography measured left ventricular mass indexed for height2.7 (LVMI2.7), and LV diastolic function from mitral E/A ratio (LVDF). LVMI2.7 ≥51 g/m2.7 and LVDF<1.5 were categorized as LV hypertrophy and LVD dysfunction, respectively. Multivariable adjusted associations were examined using generalized logit mixed-effect models and structural equation models for mediation analyses. RESULTS: The prevalence of LV hypertrophy increased from 3.6% at baseline to 11.6% at follow-up in males and increased from 1.6% to 4.0% in females. The prevalence of LVD dysfunction increased from 7.8% at baseline to 16.6% at follow-up in males and increased from 10.3% to 15.4% in females. Each 1 mmol increase in total cholesterol (OR, 1.18; [95% CI, 1.09-1.27]), triglyceride (2.89; [1.54-5.43]), LDL-c (1.19; [1.08-1.32]), and non-HDL-c (1.21; [1.11-1.33]) was associated with higher odds of worsening LV hypertrophy progression over 7 years. Increased triglyceride was associated with the odds of progressively worsening LVD dysfunction (1.98; [1.06-3.71]). Increased HDL-c was not associated with the odds of cardiac structural and functional damage. Systolic blood pressure (12% mediation) and fat mass (25% mediation) partly mediated the associations of LDL-c with increased LVMI2.7. CONCLUSIONS: Increased lipids may independently associate with the risk of progressively worsening structural and functional cardiac damage in youth but increased systolic blood pressure and fat mass explained circa forty percent of the relationship.

DXA-based Fat Mass With Risk of Worsening Insulin Resistance in Adolescents: A 9-Year Temporal and Mediation Study.

CONTEXT: Surrogate measures of childhood and adolescent obesity have impaired the understanding of the relationship of body composition with insulin resistance in the young population. OBJECTIVE: We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycemia, hyperinsulinemia, and insulin resistance from ages 15 to 24 years, the mediation path through which lipids and inflammation influence insulin resistance, and whether increased fat mass temporally precede insulin resistance. METHODS: We studied 3160 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, who had complete dual-energy x-ray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose greater than 6.1 mmol/L, insulin greater than 11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) greater than or equal to the 75th percentile were categorized as hyperglycemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed-effect models, while mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and lifestyle factors. RESULTS: Among 3160 participants (51% female), fat mass and lean mass increased linearly both in males and females, while glucose, insulin, and HOMA-IR had a U-shaped course from age 15 through 24 years. After full adjustment, each 1-kg cumulative increase in total fat mass (odds ratio 1.12 [95% CI, 1.11-1.13]) and trunk fat mass (1.21 [1.19-1.23]) from ages 15 through 24 years were associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia. The association of increased total fat mass with increased insulin resistance was partly mediated by triglycerides (9% mediation). In the temporal path analysis, higher total fat mass at age 15 years was associated with higher insulin resistance at age 17 years, but not vice versa. Higher total fat mass at age 17 years was bidirectionally associated with higher insulin resistance at 24 years. CONCLUSION: Mid-adolescence may be an optimal time for interrupting the worsening fat mass-insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood.

Accelerometer-based sedentary time, light physical activity, and moderate-to-vigorous physical activity from childhood with arterial stiffness and carotid IMT progression: A 13-year longitudinal study of 1339 children.

AIMS: We examined the longitudinal associations of sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) from childhood with carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness and carotid intima-media thickness (cIMT). METHODS: We studied 1339 children, aged 11 years from Avon Longitudinal Study of Parents and Children, UK, followed up for 13 years. Accelerometer-based ST, LPA, and MVPA were assessed at ages 11, 15, and 24 years clinic visits. cfPWV and cIMT were measured with Vicorder and ultrasound, respectively, at ages 17 and 24 years. RESULTS: Among 1339 [56.4% female] participants, mean ST increased from ages 11 through 24 years, while mean LPA and MVPA decreased. Persistently high ST tertile from childhood was associated with increased cfPWV progression, effect estimate 0.047 m/s; [(95% CI 0.005 to 0.090); p = 0.030], but not cIMT progression. Persistently high LPA tertile category was associated with decreased cfPWV progression in males -0.022 m/s; [(-0.028 to -0.017); p < 0.001] and females -0.027 m/s; [(-0.044 to -0.010); p < 0.001]. Cumulative LPA exposure decreased the odds of progressively worsening cfPWV [Odds ratio 0.994 (0.994-0.995); p < 0.0001] and cIMT. Persistent exposure to ≥60 min/day of MVPA was paradoxically associated with increased cfPWV progression in males 0.053 m/s; [(0.030 to 0.077); p < 0.001] and females 0.012 m/s; [(0.002 to 0.022); p = 0.016]. Persistent exposure to ≥60 min/day of MVPA was inversely associated with cIMT progression in females -0.017 mm; [(-0.026 to -0.009); p < 0.001]. CONCLUSION: LPA >3 h/day from childhood may attenuate progressively worsening vascular damage associated with increased ST in youth.

Longitudinal Mediating Effect of Fat Mass and Lipids on Sedentary Time, Light PA, and MVPA with Inflammation in Youth.

CONTEXT: Inflammation has been associated with atherosclerosis and metabolic disorders in youth. Preventing inflammation through exposure to different accelerometer-based movement behaviors has not been longitudinally examined. OBJECTIVE: This work aimed to examine the mediating role of fat mass, lipids, and insulin resistance on the associations of cumulative sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with inflammation. METHODS: From the Avon Longitudinal Study of Parents and Children, United Kingdom, 792 children with data on at least 2 time-point measures of accelerometer-based ST, LPA, and MVPA during age 11, 15, and 24 years follow-up clinic visits with complete high-sensitivity C-reactive protein (hsCRP) measures at age 15, 17, and 24 years were studied. Mediating associations were examined using structural equation models. When the magnitude of the association between the exposure and outcome is increased after including a third variable, suppression occurred but mediation if decreased. RESULTS: Among 792 (58% female; mean [SD] age at baseline, 11.7 [0.2] years), ST increased, LPA decreased, and MVPA had a U-shaped increase while hsCRP increased during 13-year follow-up. Insulin resistance partly suppressed (23.5% suppression) the positive associations of ST with hsCRP among participants who were overweight/obese. Fat mass partly mediated (30% mediation) the negative associations of LPA with hsCRP. Fat mass had a 77% mediation effect on the negative associations of MVPA with hsCRP. CONCLUSION: ST worsens inflammation, but increased LPA had a 2-fold inflammatory-lowering effect and was more resistant to the attenuating effect of fat mass compared with MVPA, and hence should be targeted in future interventions.

Cumulative muscle mass and blood pressure but not fat mass drives arterial stiffness and carotid intima-media thickness progression in the young population and is unrelated to vascular organ damage.

We examined the longitudinal associations of fat mass, lean mass, and blood pressure (BP) from childhood through young adulthood with changes in carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT). We included 3863 participants from the Avon Longitudinal Study of Parents and Children birth cohort. Fat mass and lean mass, measured by dual-energy X-ray absorptiometry, and BP were measured at ages 9, 17 and 24 years and classified into low, moderate, and high tertiles. cfPWV and cIMT were measured at 17 and 24 years of age. Associations were examined via linear mixed effect models and adjusted for cardiometabolic and lifestyle factors. Among 1720 [44.5%] male and 2143 [55.5%] female participants, cumulative high exposures to lean mass (effect estimate 0.006 m/s [95% CI 0.001 to 0.010; p = 0.022]), systolic BP (0.013 m/s [0.009 to 0.017; p < 0.0001]) and diastolic BP (0.023 m/s [0.019 to 0.027; p < 0.0001]) from 9-24 years of age were positively associated with the 7-year increase in cfPWV. Persistent high exposures to lean mass (0.012 mm; [0.008 to 0.016; p < 0.0001]), body mass index (0.007 mm [0.003 to 0.011; p = 0.001]), and systolic BP (0.010 mm; [0.006 to 0.014; p < 0.0001]) from ages 9-24 years were positively associated with thicker cIMT at 17-24 years of age. Total fat and trunk fat mass from childhood had no association with cfPWV or cIMT progression. In conclusion, increased lean mass and BP but not fat mass from childhood drives arterial remodeling in young adulthood.