Cumulative dyslipidemia with arterial stiffness and carotid IMT progression in asymptomatic adolescents: A simulated intervention longitudinal study using temporal inverse allocation model

Background and aimsWe aimed to examine the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) progression.MethodsWe studied 1779, 15-year-old participants from the Avon Longitudinal Study of Parents and Children, UK birth cohort, followed up for 9 years. Fasting TC, non–HDL-C, HDL-C, triglyceride, and LDL-C were measured at 15, 17, and 24 years and age-categorized as normal, elevated, and dyslipidemia based on National Heart, Lung, and Blood Institute lipid guidelines. cfPWV and cIMT were measured at 17 and 24 years. Associations were examined using linear mixed-effect models. To simulate the treatment of dyslipidemia we conducted temporal inverse allocation model analyses.ResultsAmong 1779 [49.9% female] participants, mean lipid levels and proportions at elevated or dyslipidemia categories increased from ages 15 through 24 years. Persistently elevated TC: effect estimate 0.026 mm; [95% CI 0.004 to 0.049; p = 0.024], elevated non–HDL-C, and elevated LDL-C were cumulatively associated with cIMT progression. Persistent borderline-low HDL-C: −0.027 mm; [-0.050 to −0.005; p = 0.019] and very-low HDL-C −0.035 mm; [-0.057 to −0.013; p = 0.002] levels were associated with cIMT progression. A temporal inverse allocation of elevated and dyslipidemic levels with normal lipid levels at age 17 years attenuated the associations of cumulative elevated TC, non–HDL-C, LDL-C, and low HDL-C with cIMT progression. Cumulative elevated lipids or dyslipidemia were not associated with cfPWV progression.ConclusionsLate adolescence is key to preventing, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population.</p

DEXA-based Fat Mass with the 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 body composition's relationship with insulin resistance in the young population. OBJECTIVES We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycaemia, hyperinsulinemia, and insulin resistance from ages 15-24 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 Xray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose >6.1 mmol/L, insulin >11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) ≥75th percentile were categorized as hyperglycaemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed effect models, whilst mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and other lifestyle factors. RESULTS Among 3160 participants (51% female), fat mass and lean mass increased linearly in both 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% confidence interval 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 hyperglycaemia 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 17 years, but not vice versa. Higher total fat mass at 17 years was bi-directionally 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

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: VO2peak/LM was positively associated with ΔRI in boys adjusted for age and BF% (β = 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 (β = 0.171, P = .07). BF% was inversely related to ΔRI in boys adjusted for age and VO2peak/LM (β = −0.171, P = .03). VO2peak 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.peerReviewe