Relationship of Apolipoproteins with Subclinical Cardiovascular Risk in Youth.

OBJECTIVE: To examine the association of apolipoproteins with arterial stiffness and carotid artery structure in children and adolescents. STUDY DESIGN: A total of 338 children and adolescents (178 female) with a mean age 13.0 ± 2.8 years were examined. Apolipoproteins (AI, AII, B100, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel. Applanation tonometry determined pulse wave velocity and ultrasound imaging measured carotid intima-media thickness. Dual X-ray absorptiometry measured total body fat percent. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for body fat percent. Linear regression models also examined the interaction between Tanner stage and apolipoproteins. RESULTS: There was a significant positive association between pulse wave velocity and apolipoproteins: AI (0.015 m/s/10 µg/mL [CI 0.005-0.026], P = .003), AII (0.036 m/s/10 µg/mL [0.017-0.056], P < .001), B100 (0.009 m/s/10 µg/mL [0.002-0.016], P = .012), E (0.158 m/s/10 µg/mL [0.080-0.235], P < .001), and CIII:CII (0.033/µg/mL [0.014-0.052], P < .001). After we added body fat percent to the models, pulse wave velocity (PWV) remained positively associated with greater levels of apolipoproteins: AI, AII, B100, E, and CIII:CII. Both with and without the adjustment for body fat percent, there were no significant associations between any apolipoprotein and carotid intima-media thickness. There were no significant interactions between Tanner stage and apolipoproteins. CONCLUSIONS: These findings suggest that greater levels of apolipoprotein AII, E, and CIII:CII are associated with increased arterial stiffness in children and adolescents, both with and without adjusting for percent body fat. These specific apolipoproteins may be useful as biomarkers of cardiovascular risk.

Early Life Adversity with Height Stunting Is Associated with Cardiometabolic Risk in Adolescents Independent of Body Mass Index.

OBJECTIVE: To evaluate cardiovascular and metabolic function in youths adopted internationally from orphanages/institutions (postinstitutionalized) who were height-stunted at adoption. STUDY DESIGN: A total of 30 postinstitutionalized youths (age, 9-18 years; body mass index [BMI] percentile, 7.2-90.4) who were height-stunted at adoption were compared with age- and BMI percentile-matched youths (n = 90). Measurements included total body fat and visceral adipose tissue (dual radiograph absorptiometry), arterial stiffness (augmentation index and pulse wave velocity), cardiac autonomic function (heart rate variability), blood pressure, and fasting lipid, glucose, and insulin levels. Linear regression analyses were computed controlling for parent education, age, trunk tissue fat, height-for-age, sex, and race. RESULTS: Compared with controls of the same age, sex, and BMI, the postinstitutionalized children had higher systolic blood pressure (P = .018), augmentation index (P= .033), total cholesterol (P= .047), low-density lipoprotein cholesterol (P= .03), triglycerides (P= .048), insulin (P= .005), and HOMA-IR (P= .01) values. The postinstitutionalized children had a lower low-frequency to high-frequency ratio (P = .008), indicating lower sympathetic tone, as well as a lower total lean mass (P = .016), a lower gynoid lean mass (P = .039), and a higher proportion of trunk tissue fat (P = .017). The postinstitutionalized and control children did not differ in any other body composition measures. CONCLUSIONS: Early life stress, as represented by height-stunted growth in institutional care, may be associated with early pathways to cardiovascular and metabolic risk in youths even after moving into well-resourced homes early in life and in the absence of increased adiposity. These findings suggest that postinstitutionalized youths with a history of height stunting may need to be closely monitored for emergent cardiometabolic risk factors.

Relationships of Anxiety and Depression with Cardiovascular Health in Youth with Normal Weight to Severe Obesity.

OBJECTIVE: To evaluate the relationships of depression and anxiety symptoms with cardiovascular disease (CVD) risk factors and measures of vascular health in youth. STUDY DESIGN: Participants (n = 202) were 8- to 18-year-olds from a cross-sectional study evaluating cardiovascular health across a wide range of body mass index values (normal weight to severe obesity). CVD risk measurement included blood pressure, fasting lipids, glucose, insulin, carotid artery intima-media thickness, compliance and distensibility, brachial artery flow-mediated dilation, carotid-radial artery pulse wave velocity, body fat percentage, and a metabolic syndrome cluster score. Anxiety and depression symptoms were self-reported on the Screen for Child Anxiety Related Disorders and Center for Epidemiological Studies Depression Scale for Children. Two sets of adjustment variables were used in evaluation of differences between those with and without anxiety or depression symptomatology for the CVD risk factor and vascular outcomes. The first set included adjustment for Tanner stage, sex, and race; the second was additionally adjusted for percent body fat. RESULTS: Anxiety was not significantly associated with CVD risk factors or vascular health in either model. Depression was associated with high-density lipoprotein cholesterol, triglycerides, and metabolic syndrome cluster score; these relationships were attenuated when accounting for percent body fat. CONCLUSIONS: When accounting for body fat, we found no clear relationship of self-reported depression or anxiety symptoms with CVD risk factors or vascular health in youth.

Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children.

OBJECTIVE: To determine the associations of adiposity and insulin resistance with measures of vascular structure and function in children. STUDY DESIGN: A cross-sectional study included 252 children (age 15.1 ± 2.4 years; body mass index percentile 68.2 ± 26.5%; Tanner 2-5). Measurements of body fat percentage were obtained with dual-energy X-ray absorptiometry and visceral adipose tissue (VAT) with computed tomography. Insulin resistance was measured with hyperinsulinemic euglycemic clamp. Vascular measurements for endothelial function (brachial artery flow-mediated dilation [FMD]), vascular structure (carotid intima-media thickness [cIMT]), vascular stiffness (carotid incremental elastic modulus), and pulse wave velocity were analyzed by tertiles of adiposity and insulin resistance. Additional analyses with ANCOVA and linear regression were adjusted for Tanner, sex, race, and family relationship; FMD was also adjusted for baseline artery diameter. RESULTS: FMD was positively associated with high adiposity (body mass index, body fat percentage, and VAT) (P < .01 all). Insulin resistance was not associated with FMD. cIMT was significantly, positively related to obesity, VAT, and insulin resistance (P < .05 all). No differences in carotid incremental elastic modulus and pulse wave velocity were observed in relation to adiposity or insulin resistance. CONCLUSIONS: The findings suggest that adiposity is associated with higher FMD, and insulin resistance and VAT are associated with higher cIMT in children. Further research is needed to clarify the progression of these relations.

Childhood wrist circumference is not a predictor of insulin resistance in adulthood.

We sought to determine whether childhood wrist circumference predicts insulin resistance in adulthood. Measures were taken in prepubertal children and then approximately 30 years later in the same subjects as adults. Our findings suggest that wrist circumference in childhood is not a predictor of insulin resistance in adulthood.

Cardiac autonomic dysfunction and arterial stiffness among children and adolescents with attention deficit hyperactivity disorder treated with stimulants.

OBJECTIVE: To compare markers of cardiovascular health in youth diagnosed with attention deficit hyperactivity disorder (ADHD) by the use of stimulant medication with healthy controls. STUDY DESIGN: Children and adolescents (n = 85; mean age 11.2 ± 2.8 years; 66 boys) diagnosed with ADHD using a stimulant and 53 siblings without ADHD (mean age 11.1 ± 3.8 years; 28 boys) were included in this cross-sectional study. Measured variables included blood pressure, heart rate (HR), HR variability: SD of the RR interval and low frequency to high frequency ratio, carotid-radial pulse wave velocity, carotid artery augmentation index (AIx), radial artery AIx, brachial artery flow-mediated dilation, and digital reactive hyperemic index. RESULTS: Compared with control patients, participants with ADHD had greater resting systolic blood pressure (3.9 mm Hg, 95% CI [1.2-6.7], P = .005), diastolic blood pressure (5.5 mm Hg, 95% CI [3.2-7.8], P < .001), HR (9.2 beats/min, 95% CI [6.0-12.3], P < .001), low frequency to high frequency ratio (0.55, 95% CI [0.22-0.89], P = .001), carotid AIx (7.2%, 95% CI [1.9-12.5], P = .008), and pulse wave velocity (0.36 m/s, 95% CI [-0.05, 0.78], P = .089), and lower SD of the RR interval (-33.7 milliseconds, 95% CI [-46.1, -21.3], P < .001). Neither flow-mediated dilation nor reactive hyperemic index was significantly different. CONCLUSIONS: Children and adolescents being treated with a stimulant medication for ADHD exhibited signs of altered cardiac autonomic function, characterized by increased sympathetic tone, and showed evidence of arterial stiffening.

Impact of pubertal development on endothelial function and arterial elasticity.

OBJECTIVES: Little is known about the relation of pubertal development on endothelial function and arterial elasticity in children and adolescents; therefore, we compared brachial artery flow-mediated dilation and carotid artery elasticity across Tanner (pubertal) stages in children and adolescents. STUDY DESIGN: Blood pressure, fasting lipids, glucose and insulin, body fat, insulin sensitivity adjusted for lean body mass, brachial flow-mediated dilation (percent dilation and area under the curve), endothelium-independent dilation (peak dilation and area under the curve), and carotid artery elasticity were evaluated across pubertal stages (Tanner I vs Tanner II-IV vs Tanner V) in 344 children and adolescents (184 males, 160 females; ages 6 to 21 years). RESULTS: One hundred twenty-four subjects (mean age 8.23 ± 0.15 years; 52 females) were Tanner stage I; 105 subjects (mean age 13.19 ± 0.17 years; 47 females) were Tanner stages II-IV; and 115 subjects (mean age 17.19 ± 0.16 years; 61 females) were Tanner stage V. There were no significant differences for any of the measures of vascular structure and function across pubertal stages. CONCLUSION: Results of the current study indicate that smooth-muscle and endothelial function, as well as carotid artery elasticity, do not differ throughout pubertal development and that accounting for pubertal stage when reporting vascular data in children and adolescents may be unnecessary.

Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise.

OBJECTIVES: To assess subclinical inflammation, fasting insulin, and endothelial function before and after exercise in overweight children and adolescents. STUDY DESIGN: Twenty-five children (body mass index [BMI] >85th percentile) were assessed for brachial artery flow-mediated dilation (FMD), nitroglycerin-induced dilation, C-reactive protein (CRP), lipids, glucose, insulin, oral glucose tolerance, body composition, aerobic fitness (peak oxygen uptake [VO 2 peak]), and blood pressure. Twenty of these persons were equally and randomly assigned to either 8 weeks of stationary cycling or to a non-exercising control group. RESULTS: A baseline correlation was found between CRP and fasting insulin (r = 0.62; P < .001), which remained significant after adjusting for baseline variables (r = 0.53; P < .05). After 8 weeks, significant improvements were observed in the exercise group compared with the control group for VO 2 peak (exercise group = 21.8 +/- 2.1 to 23.2 +/- 1.5 mL/kg/minute vs control group = 23.4 +/- 1.6 to 20.9 +/- 2.2 mL/kg/minute; P < .05), high-density lipoprotein (HDL) cholesterol (exercise group = 1.02 +/- 0.03 to 1.10 +/- 0.04 mmol/L vs control group = 1.08 +/- 0.07 to 0.99 +/- 0.09 mmol/L; P < .05), and FMD area under the curve (AUC) (exercise group = 746 +/- 66 to 919 +/- 94 %*sec vs control group = 731 +/- 102 to 515 +/- 73 %*sec; P < .05). CONCLUSIONS: In overweight children and adolescents, CRP is independently associated with fasting insulin. Eight weeks of aerobic exercise improves fitness, HDL cholesterol, and endothelial function in this group.