CPT1A methylation is associated with plasma adiponectin.

BACKGROUND AND AIMS: Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood. METHODS AND RESULTS: We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression coefficient ± SE = 0.01 ± 0.001, P = 3.4 × 10-13) between plasma adiponectin levels and methylation of a CpG site in CPT1A, a key player in fatty acid metabolism. The association was replicated (n = 474, P = 0.0009) in whole blood samples from the Amish participants of the Heredity and Phenotype Intervention (HAPI) Heart Study as well as White (n = 592, P = 0.0005) but not Black (n = 243, P = 0.18) participants of the Bogalusa Heart Study (BHS). The association remained significant upon adjusting for BMI and smoking in GOLDN and HAPI but not BHS. We also identified associations between methylation loci in RNF145 and UFM1 and plasma adiponectin in GOLDN and White BHS participants, although the association was not robust to adjustment for BMI or smoking. CONCLUSION: We have identified and replicated associations between several biologically plausible loci and plasma adiponectin. These findings support the importance of epigenetic processes in metabolic traits, laying the groundwork for future translational applications.

Candy consumption in childhood is not predictive of weight, adiposity measures or cardiovascular risk factors in young adults: the Bogalusa Heart Study.

BACKGROUND: There are limited data available on the longitudinal relationship between candy consumption by children on weight and other cardiovascular risk factors (CVRF) in young adults. The present study investigated whether candy consumption in children was predictive of weight and CVRF in young adults. METHODS: A longitudinal sample of children 10 years (n = 355; 61% females; 71% European-Americans, 29% African-Americans) who participated in cross-sectional surveys from 1973 to 1984 (baseline) and in one of two surveys (follow-ups) as young adults [19-38 years; mean (SD) = 23.6 (2.6) years] in Bogalusa, LA, were studied. Dietary data were collected using 24-h dietary recalls at baseline and at one follow-up survey; a food frequency questionnaire was used in the other follow-up survey. Candy consumers were those consuming any amount of candy. Candy consumption was calculated (g day(-1) ) from baseline 24-h dietary recalls, and was used as a covariate in the adjusted linear mixed models. Dependent variables included body mass index (BMI) and CVRF measured in young adults. RESULTS: At baseline, 92% of children reported consuming candy [46 (45) g day(-1)]; the percentage decreased to 67% [20 (30) g day(-1)] at follow-up. No longitudinal relationship was shown between baseline candy consumption and BMI or CVRF in young adults, suggesting that candy consumption was not predictive of health risks later in life. CONCLUSIONS: The consumption of nutrient rich foods consistent with dietary recommendations is important, although modest amounts of candy can be added to the diet without potential adverse long-term consequences to weight or CVRF. Additional studies are needed to confirm these results.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

The association of c-reactive protein with arterial compliance in asymptomatic young adults: the Bogalusa heart study.

Atherogeneis is a chronic progressive syndrome caused by endothelial dysfunction, vascular inflammation, vessel wall remodeling and eventual vascular flow compromise. Emerging data suggest that arterial compliance inversely correlates with atherogenesis and cardiovascular (CV) events. However, information is scant on the association of chronic systemic inflammation with arterial elasticity in young asymptomatic adults. The association of hsC-reactive protein (CRP) and central-vascular compliance was studied in 641 individuals (45.2% males; 71.8% whites), aged 31-43 years enrolled in the Bogalusa Heart Study. The measured variables included large-artery compliance (capacitive, C1), representative of the aorta and its major branches; and small-artery compliance (oscillatory, C2), representative of the distal part of the circulation; hsCRP, as a measure of systemic inflammation; along with traditional CV risk factor variables. Significant race and sex differences were noted for C1 (white males>black males P-value <0.0001; males>females P-value 0.04), C2 (whites>blacks P-value 0.0004; males>females P-value<0.0001) and hsCRP (blacks>whites P-value 0.03; females>males P-value 0.002). Mean values of C1 in subjects with high hsCRP levels (>3 mg l(-1)) were significantly lower than those with average (1-3 mg l(-1)) and low levels (<1 mg l(-1)) (14.2 ml per mmHg × 10 versus 15.2 ml per mm Hg × 10 versus 15.7 ml per mmHg × 10, P for trend=0.02), after adjusting for age, race, sex and body surface area (BSA). hsCRP showed a trend toward inverse correlation with C1 (-0.07, P=0.07) but no such trend for C2, after adjusting for race and sex. In the multivariate linear regression model, adding age, race, sex, BSA, mean arterial pressure, insulin resistance, lipoprotein variables and smoking status, the effect persisted between C1 and hsCRP (ß=-0.35, P=0.01). In an asymptomatic population of young adults, hsCRP predicts reduced large-artery compliance (C1). These findings support the role of systemic inflammation in early pathological changes in artery wall in atherogenesis. Small-artery compliance (C2) however did not correlate with hsCRP.

Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents.

OBJECTIVE: To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI). DESIGN AND SUBJECTS: Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8-17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites. RESULTS: In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism, rs9939609. In longitudinal multilevel models, the A/A genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the A/A genotype, BMI would be ∼0.7 kg m(-2) higher at age 8 and ∼1.6 kg m(-2) higher at age 17 than in those with A/T or T/T genotypes. The design of PHB limited follow-up of any single individual to 4 years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort. CONCLUSIONS: The A/A genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the A/A genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the BHS cohort and requires verification.

Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule.

BACKGROUND: Leukocyte telomere length (LTL) is considered a biomarker of human aging and based on cross-sectional studies it shortens with age. However, longitudinal studies reported that many adults display LTL lengthening. METHODS: Using Southern blots, we compared cross-sectional rates of age-related LTL change across a ∼20 year age range with those based on longitudinal evaluations in three surveys (S1, S2, and S3) with three time intervals: S1-S2 (5.8 years), S2-S3 (6.6 years), and S1-S3 (12.4 years). Hierarchical linear modeling was used to explore LTL dynamics using LTL data from S1, S2, and S3. RESULTS: Cross-sectionally, mean LTL shortenings were 24.6, 25.4, and 23.6 bp/y at S1, S2, and S3, respectively. Longitudinally, more variation was observed in the rate of LTL change during the shorter than longer follow-up periods. Furthermore, using simple differences in LTL, 14.4% and 10.7% of individuals displayed LTL lengthening during S1-S2 and S2-S3, respectively, but only 1.5% during S1-S3 (p < 0.001). The estimated mean rate of LTL shortening based on averaging empirical Bayes' estimates of LTL from a parsimonious hierarchical linear modeling model was 31 bp/y with a range from 23 to 47 bp/y with none of the participants showing LTL lengthening over the average 12.4 years of follow-up. CONCLUSIONS: As aging displays a unidirectional progression, it is unlikely that LTL elongates with age. LTL elongation in longitudinal studies primarily reflects measurement errors of LTL in relation to the duration of follow-up periods.

Distribution of HDL-cholesterol and non-HDL-cholesterol in Brazilian children and adolescents--the Floripa study.

BACKGROUND AND AIMS: HDL-cholesterol (HDL-C) and non-HDL-cholesterol (nHDL-C) are involved in atherosclerosis. The aim of this study was to determine the distribution of HDL-C and nHDL-C and its association with cardiovascular and socio-cultural variables in a pediatric Brazilian sample. METHODS AND RESULTS: Children and adolescents from Florianopolis were randomly selected and a structured questionnaire was administered, a physical examination was performed and a blood sample was collected. Enzymatic and Direct methods in vitro were used to determine the total cholesterol and HDL-cholesterol levels. The associations among HDL-C and nHDL-C and the described variables were tested by odds ratio and logistic regression. A total of 1009 individuals were examined. Based on the Brazilian criteria, 23% were classified with low levels of HDL-C and 25% with high levels of non-HDL-C. After multivariate analysis there were significant associations among low HDL-C and high C-reactive protein (OR, 3.3; 95% CI, 2.1-5.2), paternal tobacco use (OR, 1.5; 95% CI,1.1-2.1), and high triceps-to-subscapular index (OR, 1.5; 95% CI, 1.1-2.2). There were also significant associations among high nHDL-C and high waist circumference (OR, 1.95; 95% CI, 1.16-3.29), black skin color (OR, 1.78; 95% CI, 1.06-3.06), and high income (OR, 1.48; 95% CI, 1.09-2.02). CONCLUSIONS: In this sample, low levels of HDL-C were associated with other clinical variables such as a centripetal fat pattern and C-reactive protein, and n-HDL-C was associated with abdominal obesity, skin color and economic class.

The association of birth weight with arterial stiffness at mid-adulthood: the Bogalusa Heart Study.

BACKGROUND: Birth weight has been found to predict cardiovascular morbidity and mortality. Pulse wave velocity (PWV), a marker of arterial stiffness, has been associated with cardiovascular risk factors. An association between birth weight and blood pressure (BP) has previously been reported. In this study, the association of birth weight with PWV, and the relationship between birth weight, pulse wave velocity and BP in mid-adulthood were investigated. METHODS: The Bogalusa Heart Study (BHS) is a population-based longitudinal study to investigate the natural development of cardiovascular risk factors. In the 2001 survey, brachial-ankle PWV (baPWV) was measured as an indicator of arterial stiffness. Of the 1203 participants in that survey, 707 had complete data on birth weight and PWV, which were utilised for this study. RESULTS: In this study, birth weight was inversely correlated with baPWV, pulse pressure, and systolic and diastolic BP (r = -0.10; r = -0.10; r = -0.13 and r = -0.09, respectively; p< or =0.01 for all). After adjustment, birth weight was inversely associated with baPWV. On average, baPWV decreased by 0.23 m/s (95% CI -0.44 to -0.03 m/s) for each 1 kg increase in birth weight. Birth weight (inversely) and baPWV were independently associated with systolic BP (B = -2.05; 95% CI -3.27 to -0.84 and B = 2.99; 95% CI 2.58 to 3.40 respectively). CONCLUSIONS: Lower birth weight is associated with higher baPWV. The link between birth weight and systolic BP may be partially explained by the association of birth weight with PWV.

The contribution of childhood obesity to adult carotid intima-media thickness: the Bogalusa Heart Study.

OBJECTIVE: Although obese children are at increased risk for coronary heart disease in later life, it is not clear if the association results from the persistence of childhood obesity into adulthood. We examined the relation of both childhood and adult levels of body mass index (BMI, kg m(-2)) to carotid intima-media thickness (IMT) measured at the (mean) age of 36 years. DESIGN AND SUBJECTS: Prior to the determination of adult IMT, the 1142 participants had been examined 7 (mean) times in the Bogalusa Heart Study. MEASUREMENTS: In addition to BMI, levels of lipids, lipoproteins and blood pressure were measured at each examination. Cumulative levels of each risk factor were based on the areas under the individual growth curves calculated using multilevel models for repeated (BMI) measurements. We then examined the relation of these cumulative levels to adult IMT. RESULTS: Carotid IMT was associated with cumulative levels of BMI in both childhood and adulthood (P<0.001 for each association). Furthermore, the association between childhood BMI and adult IMT persisted, but was reduced, after controlling for adult BMI. Although childhood levels of lipids, lipoproteins and blood pressure were also associated with adult IMT, these associations were not independent of adult levels of these risk factors. CONCLUSIONS: These results emphasize the adverse effects of elevated childhood BMI levels. In addition to the strong tracking of BMI levels from childhood to adulthood, there appears to be a modest, independent effect of childhood BMI on adult IMT. The prevention of childhood obesity should be emphasized.

The association of birth weight with developmental trends in blood pressure from childhood through mid-adulthood: the Bogalusa Heart study.

Low birth weight has been found to be associated with cardiovascular mortality and morbidity and with an adverse profile of several cardiovascular risk factors. The inverse association between birth weight and blood pressure was consistently reported from many populations. Using longitudinal data from the Bogalusa Heart Study (Louisiana), the authors investigated the association between birth weight and progression of blood pressure through early adulthood, comparing that relation between African Americans and Whites. Birth data of 2,275 participants, screened two or more times in the Bogalusa Heart Study between 1973 and 2001, were retrospectively obtained from birth certificates and were linked to their clinical, laboratory, and socioeconomic and lifestyle data in the Bogalusa Heart Study data sets. Birth weight was inversely associated with systolic blood pressure, diastolic blood pressure, and pulse pressure (p

Influence of lipoprotein lipase gene Ser447Stop and beta1-adrenergic receptor gene Arg389Gly polymorphisms and their interaction on obesity from childhood to adulthood: the Bogalusa Heart Study.

OBJECTIVE: To investigate the influence of lipoprotein lipase (LPL) Ser447Stop and beta1-adrenergic receptor (ADRB1) Arg389Gly gene polymorphisms, individually and in combination, on obesity from childhood to adulthood. DESIGN AND SUBJECTS: A community-based cohort of 1331 subjects (30% black and 70% white subjects) was followed over an average period of 23 years from childhood (age range: 4-17 years) to adulthood (age range:18-44 years). MEASUREMENT: Body mass index (BMI, kg/m2) and LPL Ser447Stop and the ADRB1 Arg389Gly genotypes. RESULTS: The frequency of the ADRB1 Gly389 allele was 0.25 in white subjects vs 0.39 in black subjects (P < 0.001); 0.08 vs 0.05 (P = 0.280) for the LPL Stop447 allele. There was no association between the LPL Stop447 allele and BMI among white and black subjects either in childhood and adulthood levels or annual change from childhood to adulthood. The ADRB1 Gly389 allele was associated with lower BMI only in black adults (P = 0.017). Further, the interaction effect of the LPL Stop447 allele and ADRB1 Gly389 allele on adult BMI or its annual change was significant in white subjects and in the total sample (P = 0.03-0.006). Childhood values tended to show a similar trend. Having both ADRB1 Gly389 allele and LPL Stop447 allele was associated with 71% (95% confidence interval: 26-89%) less odds for developing obesity from childhood to adulthood after adjusting for age, race, sex, and childhood BMI. CONCLUSION: While Gly389 allele of the ADRB1 gene lowers obesity in black subjects, this allele in conjunction with Stop447 allele of the LPL gene lowers obesity in adults and attenuates the development of obesity from childhood to adulthood. These findings underscore the importance of gene-gene interaction in the assessment of genetic influences on complex traits such as obesity.

Tracking of overweight status from childhood to young adulthood: the Bogalusa Heart Study.

OBJECTIVE: To understand tracking of overweight status from childhood to young adulthood in a biracial sample. DESIGN: A longitudinal sample was created from cross-sectional surveys at two time points, childhood (baseline) and young adulthood (follow-up). SETTING: Bogalusa Heart Study, Louisiana, United States of America. SUBJECTS: A total of 841 young adults, 19-35 years (68% Euro-Americans (EA), 32% African-Americans (AA)) were studied. The same subjects had also participated in one of the five cross-sectional surveys at childhood (9-11 years). METHODS: Body mass index (BMI) was used to determine overweight status as per the Centers for Disease Control and Prevention standards. Change in the BMI status from childhood to young adulthood was used to group the participants into the following categories: normal weight to normal weight (NW-NW); normal weight to overweight (NW-OW); overweight to normal weight (OW-NW); and overweight to overweight (OW-OW). Tracking of overweight was defined by (1) correlations between baseline and follow-up BMI, (2) Cohen's kappa concordance test to determine the strength of tracking in BMI quartiles and (3) the percentage of individuals who remained in the same overweight status group from baseline to follow-up. RESULTS: From baseline to follow-up, the percentage of participants who were overweight increased from 24.7 to 57.7%. A total of 35.2% of the children shifted from normal weight in childhood to overweight in young adulthood (P < 0.0005). Baseline BMI was positively correlated with follow-up BMI (r = 0.66, P < 0.0005). A total of 61.9% of the participants in the highest BMI quartile in childhood remained in the highest BMI quartile in young adulthood. The strength of tracking in BMI quartiles was 27% for EA men (P < 0.0005), 23% for EA women (P < 0.0005), 27% for AA men (P<0.0005) and 35% for AA women (P < 0.0005). A total of 53.7% of the EA women remained in the NW-NW category and 31.2% of the AA women remained in the OW-OW category. The percentage tracking (NW-NW and OW-OW) was 72.8% in EA women, 59.6% in AA men, 59.5% in AA women and 48.8% in EA men (P < 0.0001). CONCLUSION: Childhood overweight tracked into young adulthood in this sample and the tracking of NW-NW and OW-OW was the most prominent among the EA women.

Origins of the "black/white" difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study.

BACKGROUND: The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence. METHODS AND RESULTS: Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years. CONCLUSIONS: If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.

Cardiovascular risk factors in youth with implications for aging: the Bogalusa Heart Study.

Evidence that cardiovascular (C-V) risk factors are identifiable in childhood and are predictive of future C-V risk is now irrefutable. That levels of C-V risk factors track or persist over time is important, since such phenomenon confers a life-long burden of C-V risk and indicates subtle and progressive changes in the C-V system. C-V risk factors occur often in constellation and central obesity and the attendant insulin resistance/hyperinsulinemia underlie the comorbid conditions of dyslipidemia, hypertension, thrombosis, and inflammation, among others. Autopsy studies and non-invasive subclinical C-V imaging studies in youth clearly link the multiple risk factor burdens to adverse C-V system changes. The application of multiple risk factors profiling in young individuals in conjunction with non-invasive measurements of vascular changes can promote successful aging and encourage preventive cardiology beginning in early life.

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.

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study.

OBJECTIVE: To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: : Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUC-baseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variance-component-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

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.

Inter-relationships among childhood BMI, childhood height, and adult obesity: the Bogalusa Heart Study.

OBJECTIVE: Although the body mass index (BMI, mass index, kg/m2) is widely used as a surrogate measure of adiposity, it is moderately associated (r approximately 0.3) with height among children. We examined whether the resulting preferential classification of taller children as overweight is appropriate. DESIGN: Cross-sectional analyses of children (ages, 3-17 y) examined the relation of height to adiposity (as assessed by BMI and skinfold thicknesses) and fasting levels of insulin. Longitudinal analyses examined the relation of childhood height and weight-height indices to adult (mean age, 25 y) levels of adiposity and fasting insulin. SUBJECTS: Children (n=11,406) and adults (n=2911) who had participated in the Bogalusa Heart Study. MEASUREMENTS: We constructed three weight-height indices: BMI, W/H3, and W/Hp. The triceps and subscapular skinfolds, as well as fasting levels of insulin, were also measured. RESULTS: The classification of children as overweight (BMI-for-age > or =95th percentile) varied markedly by height, with a 10-fold difference in the prevalence of overweight across quintiles of height between the ages of 3 and 10 y. Childhood height, however, was also related to skinfold thicknesses and insulin levels, and all associations were modified in a similar manner by age. Furthermore, childhood height was related to adult adiposity, and of the three childhood weight-height indices, BMI showed the strongest associations with adult adiposity. CONCLUSIONS: Because BMI reflects the positive association between height and adiposity among children, it is a better weight-height index than is either W/H3 or W/Hp.

Longitudinal changes in risk variables underlying metabolic Syndrome X from childhood to young adulthood in female subjects with a history of early menarche: the Bogalusa Heart Study.

OBJECTIVES: To examine the longitudinal changes in adiposity and related risk variables of Syndrome X from childhood to young adulthood with respect to early onset of menarche. DESIGN: Community-based longitudinal cohort of female subject (65% white, 35% blacks subjects) who participated in two or more surveys from childhood to young adulthood and had reported their menarcheal age (<12 y, n=437 vs > or =12 y, n=1042). RESULTS: In childhood (5-11 y), adolescence (12-18 y), and young adulthood (19-37 y), females with early menarche displayed significantly higher body mass index (BMI) and triceps skinfold thickness; higher stature in childhood and adolescence; higher fasting insulin and homeostasis model assessment index of insulin resistance (HOMA-IR) in childhood and adulthood; and higher fasting glucose in adulthood. Blood pressure and lipoprotein variables showed no early menarche-related differences. Longitudinal rates of change in BMI (P=0.002), triceps skinfold thickness (P=0.05), insulin (P=0.09), and HOMA-IR (P=0.05) were positive and faster among female subjects with early menarche; fasting glucose decreased slowly in this group (P=0.006). In a multivariate analysis, body fatness and insulin related independently to early menarche (P<0.001). This association was stronger in white subjects (P=0.0008). In adulthood, the prevalence of clustering of three to four risk factors of syndrome X (highest quartile of: (1) BMI, (2) fasting insulin, (3) systolic or mean arterial pressure, and (4) total cholesterol to HDL cholesterol or triglycerides to HDL cholesterol ratio specific for age, race, and study year) was higher among those with early menarche (10.7 vs 6.2%, P=0.002). The odds for developing such clustering in adulthood among those with early menarche was 1.54 (95% CI=1.14-2.07), regardless of race. CONCLUSION: Early menarche is characterized by excess body fatness and insulin beginning in early childhood and higher prevalence of clustering of adverse levels of risk variables of metabolic Syndrome X in young adulthood.