Project description:Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.
Project description:The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP), atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.
Project description:Background Microparticles and endothelial microparticles (EMPs) are implicated in accelerating cardiovascular disease (CVD); however, data in pediatrics are limited. We examined the relationship of microparticles and EMPs with adiposity and subclinical CVD risk measures in a pediatric population to determine their potential as biomarkers of CVD risk. Methods and Results A cross-sectional study of youth (n=280; ages 8-20 years) with a range of body mass index categories was used. Microparticles, EMPs, and activated EMPs were measured by flow cytometry. %Body fat and %visceral adipose tissue were measured by dual X-ray absorptiometry. Measures of arterial stiffness and vascular wall structure were obtained. Linear regression (with log-transformed outcomes) and logistic regression were used to evaluate associations and all results were exponentiated. Youth with overweight/obesity and severe obesity had 2.50 (95% CI, 1.56-4.01) and 3.42 (95% CI, 2.15-5.43) times the geometric means of the total number of microparticles, respectively, compared with those with normal weight. Youth with overweight/obesity and severe obesity had 1.97 (95% CI, 1.09-3.55) and 2.34 (95% CI, 1.31-4.19) times the geometric means of the total number of EMPs, respectively, compared with those with normal weight. There were positive associations between the levels of both microparticles and EMPs with higher adiposity measures and poor CVD risk measures. Youth with higher adiposity showed 1.84 times the odds of having high levels of activated EMPs (%) (odds ratio, 1.84; 95% CI, 1.08-3.14) compared with those with normal weight. Conclusions Levels of microparticles, EMPs, and activated EMPs were positively associated with adiposity and poor subclinical CVD risk in a pediatric population.
Project description:Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations.
Project description:This study aimed to investigate the association between the frequency of home cooking and cardiovascular disease risk among Japanese adolescents. We used cross-sectional data on adolescents from the 2018 Adachi Child Health Impact of Living Difficulty study, which targeted junior high school students aged 13-14 years in Adachi, Tokyo, Japan. Frequency of home cooking by 553 caregivers was assessed via questionnaire and classified as high (almost daily), medium (4-5 days/week), or low (≤3 days/week). Cardiovascular disease risk factors included blood pressure, serum cholesterol (total, LDL, and HDL), hemoglobin A1c, and body mass index. Multiple linear regression analysis revealed that adolescents exposed to a low frequency of home cooking showed higher diastolic blood pressure (β = 3.59, 95% confidence interval [CI]: 0.42 to 6.75) and lower HDL cholesterol (β = -6.15, 95% CI: -11.2 to -1.07) than those exposed to a high frequency of home cooking, adjusting for adolescents' sex, household income, and parental comorbidity. Future studies are needed to clarify the causal relationship and mechanisms through which home cooking influences adolescents' cardiovascular health.
Project description:Cardiovascular risk factors develop in childhood and adolescence. This enumerative review addresses whether sleep characteristics, including sleep duration, continuity, quality, and daytime sleepiness, are associated with cardiovascular risk factors in young people. Thirty-nine studies were identified, which examined the following risk factors: metabolic syndrome, glucose and insulin, lipids, blood pressure, and cardiovascular responses to psychological stressors. Due to the availability of other reviews, 16 longitudinal studies of obesity published in 2011 and later were also included in this report. Excluded from the review were studies of participants with suspected or diagnosed sleep disorders and reports from sleep deprivation experiments. Combining studies, evidence was strongest for obesity, followed by glucose, insulin, blood pressure (especially ambulatory blood pressure), and parasympathetic responses to psychological stressors. There was little evidence for metabolic syndrome cluster, lipids, and blood pressure responses to psychological stressors. The more positive associations were obtained for studies that incorporated objective measures of sleep and that included adolescents. The foundational evidence is almost entirely cross-sectional, except for work on obesity. In summary, available evidence suggests that the associations between sleep characteristics and cardiovascular risk vary by risk factor. It is time to conduct studies to determine antecedent and consequent relationships, and to expand risk factors to include markers of inflammation.
Project description:Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%. In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.
Project description:ObjectiveDiet modification is recommended to treat childhood cardiovascular (CV) risk factors; however, the optimal dietary strategy is unknown.MethodsIn a randomized trial, the effect of a low-fat (LF) and a low-glycemic-load (LGL) reduced-calorie diet were examined in youth with overweight/obesity with CV risk factors. Using a novel intervention, we delivered LF or LGL meals and nutrition education to the home for 8 weeks (Intensive Phase), followed by 4 months Maintenance without food provision. Between-group differences in the change in insulin area under the curve (InsAUC) by oral glucose tolerance test and other risk factors were analyzed.ResultsOverall, participants (n = 27) showed substantial improvement during the Intensive Phase, including InsAUC (-59 ± 18.2 µU/ml × 120 min, P = 0.004), total cholesterol (-9.9 ± 3.6 mg/dl, P = 0.01), weight (-2.7 ± 0.5 kg, P < 0.001), waist circumference (-3.1 ± 0.8 cm, P < 0.001), HOMA-IR (-1.7 ± 0.4, P < 0.001), systolic blood pressure (-5 ± 1.4 mm Hg, P = 0.002), and CRP (-0.1 ± 0.1 mg/dl, P = 0.04). There were minimal between-group differences; the LF group showed greater declines in HDL (P = 0.005) and fasting glucose (P = 0.01) compared to the LGL group. Improvements waned during Maintenance.ConclusionsHome delivery of LF or LGL diets resulted in rapid and clinically important improvements in CV risk factors that diminished without food delivery and did not differ based on dietary intervention. If scalable, food provision may represent an alternative nutrition treatment strategy.
Project description:BackgroundReductions in World Health Organization (WHO) risk drinking levels have recently been shown to lower the risk of multiple adverse health outcomes, but prior work has not examined reductions in WHO risk drinking levels in relation to cardiovascular disease (CVD), the leading cause of death for men and women in the United States and of global mortality. This study examined associations between reductions in WHO risk drinking levels and subsequent risk for CVD.MethodsIn a US national survey, 1,058 very-high-risk and high-risk drinkers participated in Wave 1 interviews (2001 to 2002) and Wave 2 follow-ups (2004 to 2005). Self-reported CVD history that was communicated to the participant by a doctor or other healthcare professionals included arteriosclerosis, hypertension, angina, tachycardia, or myocardial infarction. We used logistic regression to estimate adjusted odds ratios (aOR) evaluating relationships between ≥2-level reductions in WHO risk drinking levels from Wave 1 to Wave 2 and the risk of Wave 2 CVD, controlling for baseline characteristics.ResultsReductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD in individuals who at Wave 1 were very-high-risk (aOR = 0.58 [0.41 to 0.80]) or high-risk drinkers (aOR = 0.81 [0.70 to 0.94]). Interaction terms showed that this relationship varied by age. Among individuals >40 years old at Wave 1, reductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD among very-high-risk drinkers (aOR = 0.42 [0.28 to 0.63]) but not high-risk drinkers (p = 0.50). Among individuals ≤40 years old at Wave 1, reductions of ≥2 WHO risk drinking levels were associated with significantly lower odds of CVD among high-risk drinkers (aOR = 0.50 [0.37 to 0.69]) but not very-high-risk drinkers (p = 0.27).ConclusionsThese results show that reductions in WHO risk drinking levels are associated with reduced CVD risk among very-high-risk and high-risk drinkers in the US general population, and provide further evidence that reducing high levels of drinking provides important benefit across multiple clinical domains.