Effects of the COVID-19 Pandemic on Pediatric and Adolescent ASCVD Risk Factors.

PURPOSE OF REVIEW: In this review, we provide insight into and raise awareness of the impact of the COVID-19 pandemic on the prevalence of acquired atherosclerotic cardiovascular disease (ASCVD) risk factors in adolescents. We highlight data that could be used to guide the response to a future pandemic with the goal of reducing premature cardiovascular disease (CVD)-related morbidity and premature mortality. RECENT FINDINGS: During the global COVID-19 pandemic, many individuals, including youth, voluntarily or were mandated to alter the usual lifestyle in order to limit exposure and reduce the spread of the virus. Some of these changes resulted in unintended consequences, particularly acquisition of risk factors such as excessive weight gain, insulin resistance/diabetes, and dyslipidemia, commonly associated with ASCVD. A study from China examined changes in the prevalence of obesity and found a 2.4% rise attributable to the pandemic. Adequate daily physical activity plays an important role in ASCVD risk reduction. A systematic review and meta-analysis showed a 20% (90% CI, -34 to -4%) reduction in physical activity from before vs. during the COVID-19 pandemic. Another study of patients with type 2 diabetes found the mean HbA1c was significantly elevated during the COVID-19 pandemic (7.53 ± 1.02% in 2020) compared with the previous 2 years. In addition, there has been an alarming rise of childhood mental health concerns and suicide during the pandemic. Early identification and optimum management of CVD risk factors play an important role helping prevent future cardiovascular disease. Following the rapid spread of the virus, the World Health Organization (WHO) officially declared COVID-19 a global pandemic on March 11th, 2020. In an attempt to avoid infection and reduce the spread of the virus, many alterations in lifestyle were adopted on an international scale. While necessary, these modifications resulted in many adverse unintended health consequences in children and adolescents. This paper reviews the impact of the pandemic and the associated lifestyle changes on the prevalence of acquired atherosclerotic cardiovascular disease (ASCVD) risk factors in youth. In addition to providing insight, we hope to raise awareness of the pandemic's impact, and highlight specific data that could be used to guide the response to a future pandemic.

Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.

OBJECTIVES: To evaluate the lipid-altering efficacy and safety of ezetimibe monotherapy in young children with heterozygous familial hypercholesterolemia (HeFH) or nonfamilial hypercholesterolemia (nonFH). STUDY DESIGN: One hundred thirty-eight children 6-10 years of age with diagnosed HeFH or clinically important nonFH (low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL [4.1 mmol/L]) were enrolled into a multicenter, 12-week, randomized, double-blind, placebo-controlled study. Following screening/drug washout and a 5-week single-blind placebo-run-in with diet stabilization, subjects were randomized 2:1 to daily ezetimibe 10 mg (n = 93) or placebo (n = 45) for 12 weeks. Lipid-altering efficacy and safety were assessed in all treated patients. RESULTS: Overall, mean age was 8.3 years, 57% were girls, 80% were white, mean baseline LDL-C was 228 mg/dL (5.9 mmol/L), and 91% had HeFH. After 12 weeks, ezetimibe significantly reduced LDL-C by 27% after adjustment for placebo (P < .001) and produced significant reductions in total cholesterol (21%), nonhigh-density lipoprotein cholesterol (26%), and apolipoprotein B (20%) (P < .001 for all). LDL-C lowering response in sex, race, baseline lipids, and HeFH/nonFH subgroups was generally consistent with overall study results. Ezetimibe was well tolerated, with a safety profile similar to studies in older children, adolescents, and adults. CONCLUSIONS: Ezetimibe monotherapy produced clinically relevant reductions in LDL-C and other key lipid variables in young children with primary HeFH or clinically important nonFH, with a favorable safety/tolerability profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00867165.

Non-HDL-cholesterol in an adolescent diabetes population.

BACKGROUND: Screening for dyslipidemia poses some challenges. Nonfasting lipid profiles frequently have elevated triglycerides. In addition, in the standard lipid profile, low-density lipoprotein (LDL) cholesterol is a calculated value rather than a direct measurement and is triglyceride dependent. Non-high-density lipoprotein cholesterol (non-HDL-C) is an alternative method to assess for dyslipidemia and provides a single estimate of all atherogenic apolipoprotein B-containing lipoproteins. OBJECTIVE: To calculate the non-HDL-C in adolescents with diabetes and to evaluate risk factors associated with an elevated non-HDL-C and to compare the prevalence of dyslipidemia, defined by non-HDL-C, with the prevalence of dyslipidemia defined by LDL cholesterol in the SEARCH study. METHODS: Data were collected from 502 adolescent patients with diabetes and analyzed. Non-HDL-C was calculated and levels were categorized into normal, borderline, and high based on the National Cholesterol Education Program. RESULTS: Lipid profile was performed in 370 patients, 92% of whom had type 1 diabetes. In the 339 subjects with type 1 diabetes, mean hemoglobin A1c (HbA1c) of those with normal non-HDL-C (8.6%) was significantly lower than the HbA1c of those with high non-HDL-C (9.6%) (P = .005). Subjects with normal non-HDL-C had a lower body mass index (BMI) z-score (0.4 ± 0.8) than the group with borderline and high non-HDL-C (0.75 ± 0.9%), P = .002. In the 31 subjects with type 2 diabetes, the mean HbA1c of those with normal non-HDL-C (8.1%) and those with borderline non-HDL-C (7.0%) was significantly lower than the mean HbA1c of those with high non-HDL-C (11.8%) (P = .04, and P = .009, respectively). In addition, the subjects with normal non-HDL-C had a lower BMI z-score (1.3 ± 1.3) than the group with borderline and high non-HDL-C (2.2 ± 0.6%), P = .03. The prevalence of dyslipidemia using non-HDL-C was similar to prevalence rates using LDL-C in the SEARCH study. CONCLUSIONS: In adolescents with diabetes, non-HDL-C is increased with poorer diabetes control and higher BMI. It appears to be a superior nonfasting lipid screening test for adolescents with diabetes that can be readily calculated on a randomly obtained rather than fasting sample.

Expected body weight in adolescents: comparison between weight-for-stature and BMI methods.

OBJECTIVE: To test the hypothesis that the weight-for-stature (WFS) and BMI methods are not equivalent in determining expected body weight (EBW) in adolescents with eating disorders and to determine the sensitivity, specificity, and positive predictive value of each method to detect those <75% EBW. We hypothesized that differences in EBW would be greatest at the extremes of height. METHODS: EBW was determined for 12 047 individual adolescents aged 12 to 19 years by the WFS and BMI methods by utilizing the same National Center for Health Statistics data sets. Absolute difference between the 2 methods for each individual was calculated and plotted against height by using a generalized additive model. The number of individuals whose weights were <75% EBW was determined by each method. RESULTS: For girls, EBW was 3.52 ± 3.13% higher when using the WFS method compared with the BMI method. For boys, EBW(WFS) was 3.45 ± 2.72% higher than EBW(BMI). Among adolescent girls, 65% had EBW(WFS) higher than EBW(BMI). By using the EBW(WFS) method as the gold standard, specificity of the EBW(BMI) method to detect those <75% EBW was 0.999, but sensitivity was only 0.329. Absolute differences in EBW were most pronounced at the extremes of height. CONCLUSIONS: The WFS and BMI methods are not equivalent in determining EBW in adolescents and are not interchangeable. EBW(WFS) was ~3.5% higher than EBW(BMI). In adolescents with eating disorders, use of the BMI method will underestimate the degree of malnutrition compared with the WFS method. Which method better predicts meaningful clinical outcomes remains to be determined.

Effect of weight loss on menstrual function in adolescents with polycystic ovary syndrome.

STUDY OBJECTIVE: To compare the effects of a hypocaloric low-fat diet with those of a very low carbohydrate diet on body mass index (BMI), waist circumference (WC), and menstrual function in overweight adolescent females with polycystic ovary syndrome (PCOS). DESIGN: Randomized pilot trial of two diets in a prospective, 12-week study. SETTING: A hospital-based, academic adolescent medicine division. PARTICIPANTS: 24 females, age 12-22 years (mean 15.8 ± 2.2), with PCOS and a BMI above the 85(th) percentile for age (mean 35.7 ± 6.0 kg/m(2)). INTERVENTIONS: Nutrition counseling was given biweekly, and dietary compliance, menstrual history, and weight were recorded. WC was measured at the beginning and end of the study. MAIN OUTCOME MEASURES: Changes in weight, BMI, WC, and improvement in menstrual function over the course of the study period. RESULTS: 16 participants completed the study. 12 completers menstruated during the study period, 8 with regularity. The number of periods over 3 months increased from 0.6 ± 0.6 pre-treatment to 1.6 ± 1.3 post-treatment (P = 0.003). Overall, weight loss averaged 6.5% (P < 0.0001) and the WC decreased by an average of 5.7 ± 7.7 cm (P = 0.01). Those who lost weight were 3.4 times more likely to have improved menstrual function (P = 0.001). There were no statistically significant differences between the two groups. CONCLUSIONS: Weight loss is feasible in adolescents with PCOS and results in significant improvements in BMI, WC, and menstrual function. Weight management may be preferable as first-line treatment in adolescents, because it targets both the menstrual dysfunction and risk factors for long-term morbidity associated with PCOS.

Metabolic assessment of menstruating and nonmenstruating normal weight adolescents.

OBJECTIVE: Resumption of menses (ROM) is a key indicator of recovery in AN, but patients may remain amenorrheic despite weight restoration. The objective of this study is to better understand the mechanism of amenorrhea in patients with eating disorders. METHOD: A retrospective chart review was conducted of 382 normal weight adolescents with a history of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, who had been referred for indirect calorimetry tests. Resting energy expenditure (REE) was compared between amenorrheic (n = 60) and regularly menstruating females (n = 121). RESULTS: Participants with amenorrhea had a mean REE of 1,103 kcal/24 h (79% predicted), whereas participants who were menstruating regularly had a mean REE of 1,217 kcal/24 h (85% predicted; p = 0.001). The amenorrheic group was found to be at a lower mean body weight (53.7 +/- 5.6 kg vs. 57.5 +/- 7.4 kg; p < or = 0.001), at a lower percent ideal body weight (98.5 +/- 8.3% vs. 102.8 +/- 10.2%; p = 0.005), and at a lower BMI (20.5 +/- 1.7 vs. 21.5 +/- 2.2; p = 0.002). DISCUSSION: This study highlights that amenorrheic participants with a history of eating disorders who are at normal body weight are hypometabolic, suggesting an adaptive response to dietary restriction.

Insulin resistance and parental obesity as predictors to response to therapeutic life style change in obese children and adolescents 10-18 years old.

OBJECTIVE: To study insulin resistance and parental obesity as predictors of improvement in weight status in obese children and adolescents undergoing therapeutic life change intervention (TLC). DESIGN: A retrospective chart review. SUBJECTS: One hundred thirty-four adolescents 10 to 18 years old above the 95th percentile for body mass index (BMI), referred to the Center for Atherosclerosis Prevention from January through December 2003. MEASUREMENTS: BMI, fasting insulin, homeostasis model assessment insulin resistance (HOMA-IR). Weight management success was defined as BMI Z-score at final exam minus BMI Z-score at initial exam

Treatment goal weight in adolescents with anorexia nervosa: use of BMI percentiles.

OBJECTIVE: There is a lack of consensus as to how to determine treatment goal weight in the growing adolescent with anorexia nervosa (AN). Resumption of menses (ROM) is an indicator of biological health and weight at ROM can be used as a treatment goal weight. This study determined the BMI percentile for age at which ROM occurs. METHOD: A secondary analysis of a prospective cohort study examining 56 adolescent females with AN, aged 12-19 years, followed every 3 months until ROM. BMI percentiles for age and gender at ROM were determined using the nutrition module of Epi Info 2002. RESULTS: At 1-year follow-up, 36 participants (64.3%) resumed menses and 20 (35.7%) remained amenorrheic. Mean BMI percentile at ROM was 27.1 (95% CI = 20.0-34.2). Fifty percent of participants who resumed menses, did so at a BMI percentile between the 14th and 39th percentile. CONCLUSION: A BMI percentile range of 14th-39th percentile can be used to assign a treatment goal weight, with adjustments for prior weight, stage of pubertal development, and anticipated growth.

Screening adolescents for lipid disorders: what is the best approach?

Coronary artery disease is the most common cause of death in the United States and the leading cause of hospital-related health care costs. Hypercholesterolemia is a leading risk factor for cardiovascular disease, and both genetic and environmental factors affect cholesterol levels. Although the clinical symptoms and signs of elevated cholesterol levels in children do not occur until adulthood, arterial dysfunction and plaque formation begin much earlier. Thirty-six percent of US youth have a cholesterol level that is higher than normal (>170 mg/dL), with elevated low-density lipoprotein levels associated with atherosclerotic lesions and ultimate disease. Because the disease process begins in childhood and adolescence, early prevention in childhood is critically important. Currently, universal cholesterol screening of adolescents is the most cost-effective method of identifying individuals with familial hypercholesterolemia who need intensive and early preventive care.

Lipid and insulin levels in obese children: changes with age and puberty.

OBJECTIVE: The goal was to describe the lipid profile and insulin changes seen in obese children and adolescents at different stages of puberty. RESEARCH METHODS AND PROCEDURES: A cross-sectional study was conducted by chart review of 181 obese (BMI > 95th) children and adolescents 5 to 17 years of age, who were referred to the Center for Atherosclerosis Prevention for cardiovascular risk reduction from January 2003 through December 2003. RESULTS: Eighty (44.2%) subjects were <12 years of age, and 101 (55.8%) were >or=12 years. Severity of obesity as expressed by BMI standard deviation score did not differ between these age groups. A significant difference with lower serum levels of total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol was seen with older age and with advancing sexual maturity rating. Triglycerides, very-low-density lipoprotein cholesterol, and lipoprotein(a) levels remained elevated across age and pubertal stages. Insulin levels and insulin resistance as expressed by homeostasis model assessment were significantly higher with older age. Similar trends were observed both in obese boys and obese girls during puberty. DISCUSSION: The most striking findings of this study are that in the 5- to 17-year-old obese population, the combination of elevated triglycerides and very-low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels place them at greater cardiovascular risk than their non-obese peers, even when the changing patterns of lipids and lipoproteins seen during pubertal maturation are accounted for.

Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing.

Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Supersize teens: the metabolic syndrome.

With obesity and type 2 diabetes on the rise in children and adolescents, there has been recent interest in the study of the metabolic (insulin resistance) syndrome in this population. Characteristics of the syndrome include impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity. These features are known to cluster and convey increased cardiovascular risk over time. Screening of children and adolescents is important to the goal of prevention, and therapeutic lifestyle modification is the primary treatment modality. When this fails, pharmacotherapy aimed at the individual risk factors may be indicated.

Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial.

Osteopenia is a serious medical complication of anorexia nervosa, with no known effective treatment. We conducted a double-blinded, randomized trial comparing alendronate (10 mg daily) with placebo in 32 adolescents with anorexia nervosa (mean age, 16.9 +/- 1.9 yr). All subjects received 1200 mg elemental calcium and 400 IU vitamin D daily and received the same multidisciplinary treatment for their eating disorder. Bone mineral densities (BMDs) of the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry at baseline and after 1 yr of treatment. Twenty-nine subjects completed the study. Femoral neck and lumbar spine BMDs increased 4.4 +/- 6.4% and 3.5 +/- 4.6% in the alendronate group compared with increases of 2.3 +/- 6.9% and 2.2 + 6.1% in the control group (P = 0.41, femoral neck; P = 0.53, lumbar spine). From baseline to follow-up, BMD increased significantly at the femoral neck (P = 0.02) and lumbar spine (P = 0.02) in those receiving alendronate, but did not increase in those assigned placebo (P = 0.22, femoral neck; P = 0.18, lumbar spine). At follow-up, body weight was the most important determinant of BMD. BMD was significantly higher in subjects who were weight-restored compared with those who remained at low weight (P = 0.002, femoral neck; P = 0.04, lumbar spine). After controlling for body weight, treatment group assignment still had an independent effect at the femoral neck. We conclude that in adolescents with anorexia nervosa, weight restoration is the most important determinant of BMD, but treatment with alendronate did increase the BMD of the lumbar spine and femoral neck within the group receiving alendronate, but not compared with placebo in the primary analysis. Until additional studies have demonstrated efficacy and long-term safety, the use of alendronate in this population should be confined to controlled clinical trials.