Lipid changes 8 years post gastric bypass in adolescents with severe obesity (FABS-5+ study).

OBJECTIVE: Severe obesity in adolescents is increasing and few effective treatments exist. Bariatric surgery is one option, but the extent to which surgery influences cardiovascular risk factors over time in youth is not clear. We hypothesized that Roux-en Y gastric bypass (RYGB) would be associated with sustained improvements in lipids over time (>5 years). PARTICIPANTS/METHODS: Youth who underwent RYGB from 2001 to 2007 were recruited for the Follow-up of Adolescent Bariatric Surgery-5+ (FABS-5+) in 2011-2014. Baseline body mass index (BMI) and lipids were abstracted from medical records. Follow-up data were obtained at a research visit. Analyses included paired t-tests to assess changes in BMI and lipids over time. General linear models were used to evaluate predictors of high-density lipoprotein (HDL) and non-HDL-cholesterol at follow-up. A non-operative group was recruited for comparison. RESULTS: Surgical participants (n=58) were a mean±s.d. age of 17±2 years at baseline and 25±2 years at long-term follow-up. Eighty-six percent were Caucasian and 64% were female. At long-term follow-up BMI decreased by 29% and all lipids (except total cholesterol) significantly improved (P<0.01). Female sex was a significant predictor of non-HDL-cholesterol level at 1 year, while change in BMI from 1 year to long-term follow-up was a significant predictor of non-HDL-cholesterol and HDL-cholesterol during the same interval (P<0.05). In the non-operative group, BMI increased by 8% and lipid parameters were unchanged. CONCLUSIONS: This is the longest and most complete follow-up of youth following RYGB. Weight loss maintenance over time was significantly associated with improvements in lipid profile over 5 years.

Associations of dietary intake patterns identified using reduced rank regression with markers of arterial stiffness among youth with type 1 diabetes.

BACKGROUND/OBJECTIVES: Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile. We aimed to identify dietary intake patterns associated with CVD risk factors and evaluate their impact on arterial stiffness (AS) measures collected thereafter in a cohort of youth with T1DM. SUBJECTS/METHODS: Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, low density lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1153 youth aged ⩾10 years with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern was identified using 33 food groups as predictors and six CVD risk factors as responses in reduced rank regression (RRR) analysis. Associations of this RRR-derived dietary pattern with AS measures (augmentation index (AIx75), n=229; pulse wave velocity, n=237; and brachial distensibility, n=228) were then assessed using linear regression. RESULTS: The RRR-derived pattern was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in adverse CVD risk profile and was subsequently associated with AIx75 (ß=0.47; P<0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. CONCLUSIONS: Intervention strategies to reduce consumption of unhealthy foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS.

Insulin resistance and arterial stiffness in healthy adolescents and young adults.

AIMS/HYPOTHESIS: Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors. METHODS: We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness. RESULTS: Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx R²= 0.34; BrachD R² = 0.37; PWV R² = 0.40; all p ≤ 0.02). CONCLUSIONS/INTERPRETATION: Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. METHODS: Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. RESULTS: Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Gender differences in the relationships among obesity, adiponectin and brachial artery distensibility in adolescents and young adults.

BACKGROUND: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. METHODS: We compared brachial artery distensibility (BrachD) with APN, the level of adiposity and other CV risk factors (CVRFs) in 431 post-pubertal subjects (mean 17.9 years). Gender differences in average values were examined by t-tests. Correlations among BrachD, obesity and other CVRFs were examined. Regression analysis was performed to determine whether APN provided an independent contribution to BrachD, while controlling for obesity and other CVRFs. RESULTS: Male subjects had lower BrachD (5.72+/-1.37 vs 6.45+/-1.60% change per mm Hg, P<0.0001) and lower APN (10.50+/-4.65 vs 13.20+/-6.53; all P<0.04) than female subjects. BrachD correlated with APN (r=0.25, P< 0.0001). Both BrachD and APN correlated with measures of body size, including height, weight and body mass index (BMI). Both correlated with higher systolic blood pressure, glucose, insulin and lower high-density lipoprotein cholesterol (all P<0.01). In multivariate analysis, APN, gender, APN*gender and BMI z-score predicted BrachD (r(2)=0.305). On the basis of gender difference, only BMI z-score was significant for male subjects (r(2)=0.080), whereas APN and BMI z-score contributed for female subjects (r(2)=0.242, all P<0.0001). CONCLUSIONS: BrachD is independently influenced by obesity in both male and female subjects. In female subjects, APN exerts an additional independent effect even after adjusting for blood pressure (BP), lipid levels and insulin. Differences in the effect of the APN-adiposity relationship on obesity-related vascular disease may be one reason for gender differences in the development and progression of atherosclerosis.

Correlates of carotid artery stiffness in young adults: The Bogalusa Heart Study.

Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for prevention.

The relation of obesity throughout life to carotid intima-media thickness in adulthood: the Bogalusa Heart Study.

OBJECTIVE: Although obese children are at increased risk for coronary heart disease in later life, it is not clear if this association results from the persistence of childhood obesity into adulthood. We examined the relation of adiposity at various ages to the carotid intima-media thickness (IMT) at age 35 y. DESIGN: Prior to the determination of IMT by B-mode ultrasound, subjects (203 men, 310 women) had, on average, six measurements of body mass index (BMI) and triceps skinfold thickness (TSF) between the ages of 4 and 35 y. Mixed regression models for longitudinal data were used to assess the relation of these characteristics to adult IMT. RESULTS: Overall, adult IMT was associated with levels of both BMI and TSF (P<0.001), with the magnitudes of the associations with childhood adiposity comparable to those with adult levels of BMI and TSF. Furthermore, adult obesity modified the association between childhood adiposity and IMT: high IMT levels were seen only among overweight (BMI > or =95th percentile) children who became obese (BMI > or =30 kg/m2) adults (P<0.01 for linear trend). In contrast, IMT levels were not elevated among (1) overweight children who were not obese in adulthood, or among (2) thinner children who became obese adults. CONCLUSIONS: These results emphasize the adverse, cumulative effects of childhood-onset obesity that persists into adulthood. Since many overweight children become obese adults, the prevention of childhood obesity should be emphasized.

Screening for eligibility in the study of antihypertensive medication in children: experience from the Ziac Pediatric Hypertension Study.

BACKGROUND: The FDA Modernization Act has resulted in an increase in pediatric trials of antihypertensive medications. As experience is limited in children to guide the planning of these studies, we reviewed data from the Ziac Pediatric Hypertension Study to determine patterns of early study termination to help future studies. METHODS: For inclusion, subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase. RESULTS: Early study termination rate was 27% (38 of 140 subjects). The most common reason was screening termination due to normalization of BP, accounting for 63% of all early study terminations. Among screening termination subjects who completed three screening visits, SBP was higher (P < .001) at visit 1 (129+/-8 mm Hg) than at visit 2 (123+/-7 mm Hg) or visit 3 (121+/-8 mm Hg), but did not differ between visits 2 and 3. Screening termination occurred in 15% with isolated SBP hypertension, and 21% with isolated DBP hypertension. At randomization, 83% had SBP hypertension and 53% had DBP hypertension. CONCLUSIONS: These data suggest that SBP hypertension should be part of inclusion criteria to increase enrollment and reduce the rate of screening termination, and that 1-week placebo screening is necessary and sufficient to minimize inclusion of transiently hypertensive subjects.

Interobserver reproducibility of heart rate variability in children (the Bogalusa Heart Study).

Changes in time and frequency domain measures of heart rate variability appear to correlate with morbidity and mortality in patients with congenital heart disease. This study demonstrates that these measures are highly reproducible in children, a finding that has been previously described only in adults.

Determination of total aluminum, chromium, copper, iron, manganese, and nickel and their fractions leached to the infusions of black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by ETA-AAS.

Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated that hibiscus and mate contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g, respectively) as referred to black tea (759+/-31 microg/g) or green tea (919micro29 microg/g) and suggested that mate drinking could be a good dietary source of essential micronutrient manganese (total content 2223+/-110 microg/g, 48.1% leached to the infusion). It was also found that the infusion of hibiscus could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly related to the tannins content in the beverage (correlation coefficients > 0.82 with the exception for nickel); for lower tannins level, better leaching was observed.

Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: The Bogalusa Heart Study.

BACKGROUND: Insulin resistance, often associated with obesity, is hypothesized to be involved in the pathogenesis of essential hypertension and may relate to increased left ventricular mass (LVM). METHODS: We examined correlations between echocardiographic LVM and fasting blood glucose and insulin levels in a cross-section of 216 black and white healthy children and young adults aged 13 to 27 years in Bogalusa, Louisiana. Anthropometric measurements and blood pressure readings were also obtained. RESULTS: Positive bivariate correlation was found between fasting blood glucose level and LVM corrected for growth (LVMC) (LVMC = LVM/Height2.7) with all race/sex groups combined (r = 0.17, P

Prediction of adult hypertension by K4 and K5 diastolic blood pressure in children: the Bogalusa Heart Study.

OBJECTIVE: The objective of this study was to examine the reproducibility of K4 and K5 diastolic blood pressure measurements and the ability to predict adulthood values. STUDY DESIGN: The Bogalusa Heart Study is a long-term epidemiologic study of cardiovascular disease risk factors from birth to early adulthood conducted in the biracial (one third black, two thirds white) community of Bogalusa, Louisiana. Analyses included blood pressure measurements taken on 12,139 subjects during multiple cross-sectional screenings from 1973 to 1994; 20% (N = 2530) had measurements taken as a child, ages 4 to 18 years, and during adulthood, ages 19 to 32 years. Six resting blood pressure measurements were taken by trained observers with mercury sphygmomanometers at each screening with K1, K4, and K5 recorded. Variance components analysis was used to evaluate the reliability of K4 and K5. RESULTS: The total variance was larger for K5 (253 mm Hg2) than for K4 (109 mm Hg2) at age 5 years. Variance for both K4 and K5 decreased with age. The interobserver variability was larger for K5 (more than 50% vs 40%). Childhood K4 (vs childhood K5) was better correlated with adult K1 and K5 (0.28 vs 0.11 for K1; 0.33 vs 0.25 for K5 at age 11 to 13 years). K4 was also shown to have a higher odds ratio for predicting adult hypertension than K5 (1.57 vs 1.14 at age 11 to 13 years). CONCLUSION: During childhood K4 is a more reliable measure of diastolic blood pressure than K5. K4 diastolic blood pressure measured in childhood is a better predictor of adult hypertension.

Ethnic (black-white) contrasts in heart rate variability during cardiovascular reactivity testing in male adolescents with high and low blood pressure: the Bogalusa Heart Study.

Heart rate variability (HRV) is used to study autonomic effects on the heart. The time domain PNN50 (percentage of consecutive RR intervals differing by > 50%) measures high frequency in HRV primarily reflecting parasympathetic activity. The ratio of low to high frequency power (LF/HF) measured by fast Fourier analysis is used to measure sympathetic to parasympathetic balance. In adults, increased sympathetic tone has been found in hypertensive individuals. The present study was performed to look for differences in HRV by race and between subjects with high and low blood pressure (BP). Heart rate variability data was analyzed from Holter monitor recordings in 39 healthy male subjects aged 13 to 17 years (50% white). Half were selected with Korotkoff fourth sound (K4) DBP > 85th percentile for height measured twice, 3 to 5 years apart (average 116/75 mm Hg). Half had DBP < 15th percentile for height (average 101/57 mm Hg). Subjects underwent a physical examination including BP, height, and weight before cardiovascular reactivity testing including measurements taken while supine and standing, and during 20% maximal isometric hand grip, Valsalva maneuver, and immersion of the hand in water at 4 degrees C. The LF/HF ratio was significantly higher and the PNN50 was significantly lower in whites compared with ratios for blacks during all CV reactivity tests (all P < .05). There was a trend for higher LF/HF ratio and lower PNN50 in blacks and whites with higher levels of BP, although this did not reach statistical significance. It was concluded that healthy white adolescents exhibit increased sympathetic tone compared with that of blacks during CV reactivity tests. A trend towards sympathetic predominance during reactivity testing was demonstrated in children with higher levels of DBP.

The role of the pediatrician in the promotion of cardiovascular health.

The subspecialist has been historically on the forefront of diagnosis and management of cardiovascular disease in our society. Recently, however, we have seen the focus shifting from high technology to include primary care and prevention. Cardiovascular risk evaluation has been identified as the thrust of the 1990s, and there is a reemergence of the generalist as a potential leader in cardiovascular care. It is now recognized that efforts early in life to promote cardiovascular health may have dramatic impact beyond the pediatric age. Five major areas are identified as targets for cardiovascular health promotion in childhood: obesity, cardiovascular fitness, hypertension, hypercholesterolemia, and smoking prevention. Pediatricians, as well as family physicians, must recognize their critical role in the promotion of cardiovascular health. The focus should not be limited to traditional childhood diseases but also to adult diseases that have their origins in childhood. Appreciation of the scientific findings generated by studies such as the Bogalusa Heart Study should influence the pediatrician in assuming a major role in prevention of adult heart and other chronic diseases.

Comparison of fourth and fifth Korotkoff diastolic blood pressures in 5 to 30 year old individuals. The Bogalusa Heart Study.

The use of fourth phase Korotkoff sound (K4) versus fifth phase Korotkoff sound (K5) for the determination of diastolic blood pressure (DBP) has been a subject of controversy since the indirect method of determining arterial blood pressure was described. Using data from the Bogalusa Heart Study, we evaluated the differences between K4 and K5 (K4-K5) from 4633 subjects 5 to 30 years of age examined between 1987 and 1991. The overall mean difference between K4 and K5 was 9.9 +/- 5.6 mm Hg (mean +/- SD). The average difference was highest in 5 to 8 year olds, where it measured 12.3 +/- 5.5 mm Hg. The average K4-K5 difference fell with increasing age and reached a value of 6.3 +/- 2.6 mm Hg by 25 years of age. For all race/sex groups, the youngest two age groups differed statistically from the oldest age groups in K4-K5 difference (P < .006). There were significant differences between blacks and whites (P < .015) and between men and women (P < .001) for subjects between 13 and 17 years of age. Additional analyses were performed with individuals having K5 = 0 added to yield an expanded population of 5117 persons. Overall, 9.5% had at least one of six measurements of K5 = 0 and most were young subjects: 27% of children 5 to 8 years and 13% of children 9 to 12 years. We conclude that by age 15 there may be no relevant clinical difference in K4-K5. However, in children, K4 and K5 should be recorded and K4 is a more reproducible measure of diastolic blood pressure.

Effect of body size, ponderosity, and blood pressure on left ventricular growth in children and young adults in the Bogalusa Heart Study.

BACKGROUND: The measurement of left ventricular mass (LVM) is important because individuals with increased LVM are at increased risk for cardiovascular diseases, including myocardial infarction and congestive heart failure. There are limited longitudinal data on the acquisition of LVM in children and young adults and the relative importance of sex, growth, excess body weight, and blood pressure (BP) on change in LVM. METHODS AND RESULTS: The study cohort consisted of a cross section of 160 healthy children and young adults 9 to 22 years of age at first exam in the biracial community of Bogalusa, La. All had stable BP levels recorded over a 2- to 3-year period. Repeated examinations were performed 4 to 5 years apart. At each exam, 6 BPs were obtained with a mercury sphygmomanometer by trained examiners. The mean of the observations was used, with the fourth Korotkoff phase serving as the measure of diastolic BP. Anthropometric data, including height (HT), weight (WT), and triceps skin fold thickness (TSF), were also obtained, and M-mode echocardiograms were performed. Ponderal index (PI = WT/HT3) was used as a measure of weight-for-height. Tracking of HT (r = .68 to .76), WT (r = .73 to .82), PI (r = .77 to .89), TSF (r = .70 to .80), BP (r = .47 to .60), and LVM (r = .40 to .70) was strong in both sexes (P < .0001). LVM indexed for linear growth (LVM/HT2.7) tracked in females (r = .56, P < .0001) but not in males. In univariate cross-sectional analyses, LVM/HT2.7 correlated with WT, PI, and TSF in both sexes (r = .21 to .60, P < .05) and with systolic BP (SBP) in females (r = .23, P < .05). WT was the only independent correlate of LVM/HT2.7 in both sexes in multivariate cross-sectional analysis in a model containing age, SBP, WT, and TSF as independent variables (r2 = .08 to .28, P < .02). In longitudinal univariate analyses, initial measurements of WT, PI, and TSF predicted final LVM/HT2.7 in both sexes (r = .28 to .56, P < .01), and SBP was significant for females (r = .27, P < .05). In multivariate analyses, initial WT was associated with final LVM and LVM/HT2.7 in both sexes (r2 = .27 to .54, P < .01). Finally, baseline LVM correlated with final SBP in both sexes (r = .21 to .27, P < .05), and initial LVM/HT2.7 correlated with final SBP in females (r = .26, P < .05) with a trend for males (r = .17). CONCLUSIONS: These data indicate that linear growth is the major determinant of cardiac growth in children and that excess weight may lead to the acquisition of LVM beyond that expected from normal growth. Increased mass may also precede the development of increased BP. The development of obesity may therefore be a significant, and possibly modifiable, risk factor for developing left ventricular hypertrophy and hypertension, risk factors for cardiovascular morbidity and mortality.