Comorbidity

Dyslipidemia and Pediatric Obesity

Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities.

Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity.

Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured.

The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01).

Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.

Abnormal lipid profiles in adolescents predict metabolic and cardiovascular diseases in adulthood. While seafood consumption is the primary source of mercury exposure, it also provides beneficial nutrients such as omega-3 fatty acids (O3FA). Prior studies indicate that blood total mercury (TBHg) has endocrine disrupting effects and may be associated with abnormal lipid profiles in adolescents. However, the impact of beneficial nutrients on this relationship has not been examined. Our study investigated the relationship of TBHg with dyslipidemia and lipid profiles and potential confounding and modification of these relationships by sex, body mass index (BMI), selenium and O3FA from seafood consumption.

We examined 1,390 National Health and Nutrition Examination Survey participants 12-19 years of age from the 2011-2018 cycles. Using logistic and linear regression adjusted for survey design variables and stratified by sex a priori, we estimated the associations of TBHg and methylmercury with dyslipidemia, and with total cholesterol (TC), high (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and triglycerides.

The geometric mean of TBHg in this adolescent population was 0.44 µg/L. After controlling for sociodemographic covariates, BMI, serum selenium, age at menarche (females only) and average daily intake of O3FA; TBHg was significantly associated with higher TC levels (β=3.34, 95% CI: 0.19, 6.50; p<0.05) in females but not males. Methyl Hg was also associated with increased TC, as well as decreased HDL-C in females but not males. We did not find significant associations of Hg exposure with dyslipidemia, LDL-C or triglycerides levels in either male or female adolescents. However, we observed evidence of effect modification by BMI and serum selenium for associations of TBHg with TC levels in male and female adolescents, respectively.

Our findings of elevated TC levels in females but not males necessitates further research to better understand the underlying mechanisms driving these sex-specific associations.

Obesity is a metabolic disorder that is defined as excessive increase in body fat tissue. Early recognition of obesity in children is essential to prevent complications that may occur in both childhood and adulthood.

The purpose of this study was to assess cardiometabolic risk and to investigate the association between novel biomarkers and cardiovascular disease in obese children.

This research was performed between June 2014 and January 2015 in the Pamukkale University Faculty of Medicine. Fifty obese children and, 29 healthy children were included in the study. Fasting levels of serum lipids, glucose and insulin, serum copeptin, BNP, and ADM were measured. Thickness of main CIMT and EAT were assessed with 2D echocardiogram. M-mode echocardiographic measurements, mitral and tricuspid valve measurements with PDE, and tricuspid and interventricular septum measurements with TDE were performed in both groups. Treadmill stress testing was performed in the same patient group.

Levels of total cholesterol and LDL were significantly higher in obese group. Serum BNP and serum ADM levels were significantly lower in obese group. Left ventricular mass index, CIMT and EAT were statistically higher in obese group. Left ventricular end-systolic diameter, left ventricular end-diastolic diameter, interventricular septum diameter, posterior wall thickness were significantly higher in obese group than in control group. Time to reach target heart rate in treadmill stress testing was significantly shorter in obese group than in control group.

Childhood obesity is associated with significant changes in the myocardial structure based on echocardiography. Thickness of carotid intima-media and epicardial fat tissue can be used as predictive markers of atherosclerosis in obese children. Our study demonstrated that exercise capacity is significantly lower, and hemodynamic response to exercise is defective in obese children.

The efficacy of lipid-lowering therapy in reducing cardiovascular disease in adults is well-established. Unfortunately, it is also well-established that adults have inadequate adherence to lipid-lowering therapy, which is associated with increased costs and mortality. However, the adherence patterns of youth prescribed lipid-lowering therapy is not well-described.

We analyzed data that was prospectively collected from patients <27 years-old who were referred to a large regional preventive cardiology clinic from 2010 to 2017. Adherence to lipid-lowering therapy was self-reported at the patient's most recent clinic visit and categorized as either adequate adherence (≥80%) or inadequate adherence (<80%). We compared adherence rates by demographic factors, class of lipid-lowering therapy, length of time on lipid-lowering therapy, family history, lipid parameters, and laboratory measures of adverse effects.

In our cohort, we had 318 patients prescribed a lipid-lowering medication over a seven-year period. Of those, 235 (75%) had adequate adherence. Those with adequate adherence had an improved LDL-C (123 mg/dL [standard deviation (SD) 32.3] vs. 167 mg/dL [SD 50.4], p < 0.05), total cholesterol (198 mg/dL [49.5] vs. 239 mg/dL [SD 53.2]), and non-HDL-C (148 mg/dL [SD 38.7] vs. 193 mg/dL [SD 43.9]). In addition, patients with adequate adherence were more likely to reach goal LDL-C of <130 mg/dL than those with inadequate adherence (130 vs. 25, p < 0.01). The relationship between LDL-C and adherence remained statistically significant after controlling for age, gender, and the length of time on therapy (β = −0.66, p < 0.01). Adherence level did not differ by gender, class of lipid-lowering therapy, length of time on lipid-lowering therapy, or presence of a family history of an atherosclerotic event. The findings were similar when we only analyzed those prescribed a statin.

Self-reported adherence to lipid-lowering therapy in youth is excellent and was associated with achieving goal LDL-C goals. Obtaining adherence data from patients may help more patients reach LDL-C goals.

Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth.

The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls.

Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children’s hospitals (Children’s Hospital of Philadelphia and the Children’s National Health System in Washington, DC).

CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses.

The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected.

Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score.

Compared with controls (n = 100, median age = 14.8 years [interquartile range = 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n = 143, median age = 14.7 years [interquartile range = 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range = 46.8 to 58.6] vs controls: 45.1 [interquartile range = 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (–0.14, 95% CI –0.29 to 0.00; P = 0.053).

Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.

A heart-healthy lifestyle, beginning at an early age and sustained throughout life, may reduce risk for cardiovascular disease in youth. Among youth with moderate to severe dyslipidemia and/or those with familial hypercholesterolemia, lipid-lowering medications are often needed for primary prevention of cardiovascular disease. However, lifestyle interventions are a foundation for youth with dyslipidemia, as well as those without dyslipidemia. There are limited data supporting the use of dietary supplements in youth with dyslipidemia at this time. A family-centered approach and the support of a multi-disciplinary healthcare team, which includes a registered dietitian nutritionist to provide nutrition counseling, provides the best opportunity for primary prevention and improved outcomes. While there are numerous guidelines that address the general nutritional needs of youth, few address the unique needs of those with dyslipidemia. The goal of this National Lipid Association Clinical Perspective is to provide guidance for healthcare professionals caring for youth with disorders of lipid and lipoprotein metabolism, including nutritional guidance that complements the use of lipid lowering medications.