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PurposeBirth weight (BW) is associated with risk of cardiovascular (CV) disease. The findings form studies examined the association of BW with metabolic markers of CV risk were inconsistent and controversial. We examined the association of BW with insulin resistance and blood lipids using repeated measures up to mid-adulthood.MethodsData from seven screenings of the Bogalusa Heart Study—a longitudinal study of cardiovascular risk factors in Bogalusa, LA, are analyzed using generalized estimation equations method. Participants with birth data and at least one measurement of study outcomes between 18-44 years of age (n=2,034) were included.ResultsBW is inversely associated with insulin resistance, triglycerides and total cholesterol (PConclusionsThe study provides strong evidence of an inverse relationship of BW with adulthood cardiometabolic risk profile. Persons born with low BW are maybe less responsive to preventive interventions aiming at weight reduction.

Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. The PROG-IMT project, which includes this publication, has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, www.dfg.de) under the grants DFG Lo 1569/2-1 and DFG Lo 1569/2-3, received by MWL. The DFG had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Thompson is supported by the British heart Foundation (CH/12/2/29428). Some of the contributing studies were funded by different parties, as listed in the acknowledgement section. Here, too, the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

The early onset of menarche is related to the adulthood risk of cardiovascular (CV) disease. This study examines the relation of early onset of menarche to carotid artery intima-media thickness (IMT), which is a surrogate marker of CV disease, among asymptomatic young adult women in a black-white community.A cohort of 461 women (31% black, 69% white) aged 24 to 43 years (mean of 35.6 years) were participants in the Bogalusa Heart Study. The age at menarche was retrospectively collected. In addition to CV risk factor variable measurements B-mode ultrasound images of the far walls of carotid artery segments were obtained. The multivariate linear regression model along with mediating effect by Sobel test was applied to analyze menarcheal age effect on carotid artery IMT, adjusting for covariates.Waist to height ratio was significantly greater (P = .01) in early menarcheal age (11 years) versus menarcheal age (≥11 years) in both black and white women. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly greater (P = .01) in early menarcheal age (11 years) versus menarcheal age (≥11 years) in white women and also similar direction in black women. Internal carotid artery IMT was the same in early menarcheal age (11 years) versus menarcheal age (≥11 years) in white women but higher (P = .02) in black women. Given as previously mentioned these different associations, the mediation analysis by race was performed. The effect of early menarcheal age (11 years) versus menarcheal age (≥11 years) was mediated by waist to height ratio and HOMA-IR in white women after adjusting for parental education and age. The mediating effect of waist to height ratio (Sobel test = -2.26 and P = .02) and HOMA-IR (Sobel test = -1.85 and P = .06) on internal carotid artery IMT was noted in white women. The direct effect of early menarcheal age (11 years) versus menarcheal age (≥11 years) on internal carotid artery IMT (β = -0.150, P = .01) was observed in black women.The observed deleterious effect of early onset of menarche on carotid artery IMT in asymptomatic black and white younger adult women has biological, social, and public health implications.

Secondhand smoke (SHS) exposure increases cardiovascular disease risk. The objective of this study was to examine the association of SHS exposure in childhood and adulthood with adult arterial thickness.The study cohort consisted of 415 nonsmoking adults (301 whites and 114 blacks; ages 26.2-48.0 years) enrolled in 2004-2010. The arterial wall thickness was measured as common, bulb and internal carotid artery intima-media thickness (IMT). SHS exposure data in childhood and adulthood were obtained by a questionnaire survey.Increased adult composite carotid IMT was significantly associated with SHS exposure (regression coefficient, β = 53.1 μm, p 0.001) after adjusting for race, age, gender, education, income, body mass index, systolic blood pressure, LDL cholesterol and triglycerides/HDL cholesterol ratio, with blacks (β = 81.2 μm, p = 0.005) and whites (β = 38.9 μm, p = 0.017) showing the same direction of the association. Furthermore, the SHS exposure in childhood showed a relatively stronger association with increased carotid IMT than the exposure in adulthood based on standardized βs (0.180 vs. 0.106); the same trend in the difference between childhood and adulthood exposure was noted for duration of SHS exposure (0.186 vs. 0.145). The covariates-adjusted composite carotid IMT showed a significant increasing trend by the order of exposure status of none, adulthood only, childhood only and both (p for trend0.001).If the relationship is causal, the associations observed in this study suggest that more awareness should be raised on the dangers of SHS exposure during childhood so that its effect may be mitigated and controlled early in the cardiovascular disease process.

Objectives To examine the associations of five GWAS-identified genes with carotid intima-media thickness (IMT) in a biracial sample from the Bogalusa Heart Study, and evaluate their participation in gene-smoking interactions. Methods Far wall IMTs of common carotid arteries were measured using high-resolution B-mode ultrasound. Both the gene-smoking interactions and single-marker associations were evaluated by linear models of carotid IMT levels, while the gene-based analyses were assessed through the truncated product method. A Bonferroni multiple testing correction was applied. Results Marker rs7840785 ( PINX1 ) was significantly associated with right carotid IMT (p = 0.0003) using all participants; mean levels for the CC, TC, and TT genotypes were 0.74 (0.73 to 0.75), 0.76 (0.75 to 0.78), and 0.78 (0.75, 0.81), respectively. Similar trends were observed in blacks (p = 0.0031) and whites (p = 0.0118). Marker rs7844465 ( ZHX2 ) was significantly associated with left carotid IMT in whites (p = 0.0005); mean IMT levels for the GG, TG, and TT genotypes were 0.73 (0.71 to 0.74), 0.75 (0.74 to 0.77) and 0.78 (0.75 to 0.81), respectively. Marker rs6841473 ( EDNRA ) modified the association between smoking and left carotid IMT in blacks (p = 2.79 × 10 − 5 ). In addition, gene-based analysis demonstrated that EDNRA and ZHX2 were associated with left carotid IMT in the white and overall participants, respectively, while PINX1 was associated with right carotid IMT in both blacks and whites. Conclusion We identified two novel markers that were associated with IMT in both blacks and whites. One gene-smoking interaction was identified in blacks only. Three genes showed gene-based associations with IMT levels. However, genetic markers with small effects may have been missed due to the limited number of black participants.

Background: Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity ...

Background— Elevated blood pressure (BP) levels in childhood have been associated with subsequent atherosclerosis. However, it is uncertain whether this risk is attenuated in individuals who acquire normal BP by adulthood. The present study examined the effect of child and adult BP levels on carotid artery intima-media thickness (IMT) in adulthood. Methods and Results— The cohort consisted of 4210 participants from 4 prospective studies (mean follow-up, 23 years). Childhood elevated BP was defined according to the tables from the National High Blood Pressure Education Program. In adulthood, BP was classified as elevated for individuals with systolic BP ≥120 mm Hg, diastolic BP ≥80 mm Hg or with self-reported use of antihypertensive medications. Carotid artery IMT was measured in the left common carotid artery. High IMT was defined as an IMT ≥90th percentile according to age-, sex-, race-, and cohort-specific levels. Individuals with persistently elevated BP and individuals with normal childhood BP, but elevated adult BP had increased risk of high carotid artery IMT (relative risk [95% confidence interval]) 1.82[1.47–2.38] and 1.57[1.22–2.02], respectively) in comparison with individuals with normal child and adult BP. In contrast, individuals with elevated BP as children but not as adults did not have significantly increased risk (1.24[0.92–1.67]). In addition, these individuals had a lower risk of increased carotid artery IMT (0.66[0.50–0.88]) in compared with those with persistently elevated BP. The results were consistent when controlling for age, sex, and adiposity and when different BP definitions were applied. Conclusions— Individuals with persistently elevated BP from childhood to adulthood had increased risk of carotid atherosclerosis. This risk was reduced if elevated BP during childhood resolved by adulthood.

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.

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

This is a consortium of large children's cohorts that contain measurements of major cardiovascular disease (CVD) risk factors in childhood and had the ability to follow those cohorts into adulthood. The purpose of this consortium is to enable the pooling of data to increase power, most importantly for the follow-up of CVD events in adulthood. Within the consortium, we hope to be able to obtain data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence.

© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

Background More than 600 deaths of all causes have been documented over the 40-year duration of the Bogalusa Heart Study. Of these, 97 deaths have been related to cardiovascular events, based on obituaries published in local newspapers, death certificates obtained from the State Health Department, information from the coroner and word of mouth by nursing staff from the community. Methods This study was a retrospective longitudinal cohort with several observations of each subject. It consisted of 6 cross-sectional surveys of children aged 5-7 years, conducted between 1973 and 1988, and 4 cross-sectional surveys of previously examined subjects as young adults extending into middle age, conducted between 1988 and 2010. Results Excluding pulmonary, congenital and noncoronary cardiovascular diseases, 46 deaths (average age at death = 44.7 years, range: 31-55) were considered to have been related to coronary artery disease, that is, myocardial infarction. Cardiovascular risk factor observations, gathered from multiple surveys (average of 4.4 surveys, range: 1-14) since childhood, indicated that body fatness and elevated blood pressure beginning in childhood were more common in subjects who later died of coronary artery disease than in living subjects. Conclusions The present findings emphasize that sub-clinical cardiovascular disease begins early in life and that early prevention is vital.

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. © 2012 The American Society of Human Genetics.

Background— The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results— We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9–1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1 , and TBX5 to African American populations at the genome-wide significance level ( P −8 ), we also identified a novel locus: ITGA9 , located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR ( P −8 ). Conclusions— This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.

Background— Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and Results— First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval ( P =0.94). Genome-wide significant associations ( P –8 ) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P =2×10 –15 ) and ATP1B1 (rs1320976, P =2×10 –10 ). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values ( P –5 ) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1 , KCNH2 , LITAF , and PLN . Conclusions— We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

Objectives: The aim of this study was to examine the effect of resolution from metabolic syndrome (MetS) between youth and adulthood on carotid artery intima-media thickness (IMT) and type 2 diabet...

The association between birth weight and long-term within-individual variability of blood pressure (BP) was examined in a longitudinal cohort of 1,454 adults (939 whites and 515 blacks; adulthood age = 19–50 years) enrolled in the Bogalusa Heart Study in Bogalusa, Louisiana, in 1973–2010. BP variability was depicted as standard deviation, coefficient of variation, and deviation from age-predicted values using 6–15 serial BP measurements from childhood to adulthood over an average of 25.7 years. Birth weight was significantly and negatively associated with adulthood BP levels, long-term BP levels, and rate of change. Importantly, low birth weight was significantly associated with increased BP variability in terms of standard deviation, coefficient of variation, and deviation. As evaluated using the regression coefficients, a 1-kg lower birth weight was associated with increases in systolic BP variability measures (−0.38 mm Hg, P = 0.04 for standard deviation; −0.004 mm Hg, P = 0.01 for coefficient of variation; and −0.16 mm Hg, P = 0.04 for deviation) after adjustment for race, age, sex, mean BP levels, and gestational age; similar trends in the associations were noted for diastolic BP variability measures. In conclusion, these findings suggest that birth weight affects not only BP levels but also the magnitude of within-individual BP fluctuations over time through fetal programming in BP regulation mechanisms.

FTO affects changes in BMI during both childhood and adulthood. However, its effect on onset age of overweight in adulthood is not known. To address this question, we conducted a study to examine effects of FTO tag SNPs on censored age of overweight in the longitudinal Bogalusa Heart Study (BHS) cohort, which began in 1973-1974. Of participating subjects, 658 whites (308 males and 350 females) with genotype data were selected for the study. The FTO gene was examined by a survival analysis of 30 tag SNPs regarding their association with left, interval and right-censored adult overweight. After adjustment for birth weight and sex, SNP rs9939609 has a small nominal p value of 0.004 for the association with onset age, which has an expected proportion of false positives of 9.6 % after adjusting for multiple tests. It was estimated that genotypes AA, AT and TT have onset age (standard error) of 22.82 (1.07), 28.96 (1.04) and 27.76 (1.04) years, respectively, for a 50 % cumulative proportion of overweight in the population. Genotypes AA, AT and TT, respectively, have estimated survival probability of 65.8, 78.7 and 76.8 % at the age of 18; and survival probability of 6.5, 11.8 and 10.7 % at the age of 60. The odds ratios of survival beyond age ≥18 years are 0.52 for AA versus AT and 0.58 for AA versus TT. We thus concluded that risk genetic variants at FTO gene can accelerate the onset age and influence the survival odds of overweight in younger adults.

OBJECTIVE The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults. RESEARCH DESIGN AND METHODS This prospective cohort study consisted of normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18–50 years who were followed for an average of 16 years. RESULTS The incidence rate of the onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for age-groups 18–29, 30–39, and 40–50 and total sample, respectively. Incidences of diabetes increased with age by race and sex groups (P for trend ≤0.01); higher in black females versus white females and blacks versus whites in total sample (P < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio [HR] 5.24) and plasma insulin were significantly associated with diabetes incidence at the youngest age (18–29 years); black race, BMI, and glucose at age 30–39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40–50 years; and black race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole cohort. Further, patients with diabetes, regardless of age onset, displayed a significantly higher prevalence of maternal history of diabetes at baseline (P < 0.01). CONCLUSIONS In relatively young adults, predictability of baseline cardiometabolic risk factors along with race, sex, and parental history of diabetes for the onset of type 2 diabetes varied by age-group. These findings have implications for early prevention and intervention in relatively young adults.

Introduction Gender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness (IMT) has not been studied in a biracial (black-white) community-based asymptomatic young adults. Methods Femoral IMT was measured by B-mode ultrasonography in 1080 individuals (age, 24–43 years; 71% white; 43% men) enrolled in the Bogalusa Heart Study. Results Femoral IMT showed a gender difference (men > women; P = 0.001), but no racial difference. In a multivariate model, age, cigarette smoking, systolic blood pressure and total cholesterol to high-density lipoprotein cholesterol ratio related independently, in that order, to IMT in women, and age and low-density lipoprotein cholesterol in men. In women, mean IMT increased with increasing number of risk factors defined as values above the age-, race- and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol to high-density lipoprotein cholesterol ratio and insulin along with positive smoking status ( P for trend = 0.001), with respective mean IMT (mm) values of 0.61, 0.65, 0.72 and 0.77, for 0, 1 to 2, 3 and 4 to 5 risk factors. There was no such significant trend in men. Conclusions Although men versus women had thicker IMT, the observed increasing trend of femoral IMT with increasing number of risk factors in asymptomatic young women suggests that women may be relatively more susceptible to the burden of multiple risk factors.

Clinical relevance of a genetic predisposition to elevated blood pressure was quantified during the transition from childhood to adulthood in a population-based Finnish cohort (N=2357). Blood pressure was measured at baseline in 1980 (age 3–18 years) and in follow-ups in 1983, 1986, 2001, and 2007. Thirteen single nucleotide polymorphisms associated with blood pressure were genotyped, and 3 genetic risk scores associated with systolic and diastolic blood pressures and their combination were derived for all of the participants. Effects of the genetic risk score were 0.47 mm Hg for systolic and 0.53 mm Hg for diastolic blood pressures (both P P =0.015). Replications in 1194 participants of the Bogalusa Heart Study showed essentially similar results. The participants in the highest quintile of the combination genetic risk score had a 1.82-fold risk of hypertension in adulthood ( P

OBJECTIVE Elevations in alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of metabolic syndrome and related type 2 diabetes. However, information is limited regarding the long-term predictability of ALT and GGT in the development of prediabetes and type 2 diabetes. RESEARCH DESIGN AND METHODS In this retrospective cohort study, normoglycemic (n = 874), prediabetic (n = 101), and diabetic (n = 80) adults aged 26–50 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 18–38 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT. RESULTS The follow-up prevalence rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed an adverse trend for both prediabetes (P < 0.05) and diabetes (P < 0.01). In a longitudinal multivariate logistic regression analysis that included anthropometric, hemodynamic, and metabolic variables, as well as alcohol consumption and smoking, individuals with elevated baseline ALT and GGT levels (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to develop diabetes (P = 0.05 for ALT and P < 0.01 for GGT); no such associations were noted for prediabetes. Regarding the predictive value of ALT and GGT, the area under the receiver operating curve analysis yielded C values ranging from 0.70 to 0.82, with values significantly higher for diabetes compared with prediabetes. CONCLUSIONS These findings in younger adults suggest potential clinical utility of including ALT and GGT as biomarkers in diabetes risk assessment formulations.

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 (SNP), 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 approximately 0.7 kg/m2 higher at age 8, and approximately 1.6 kg/m2 higher at age 17 than in those with A/T or T/T genotypes. The design of Project HeartBeat! limited follow-up of any single individual to four 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 Bogalusa Heart Study cohort and requires verification.

Blood pressure (BP) is a highly variable physiologic trait with short-term and long-term fluctuations within the same individual at different time points. The burden of BP on the cardiovascular (CV) system has been studied in terms of multiple cross-sectional BP measurements at rest, response of BP to stresses, and long-term longitudinal variability of BP. Observations from childhood are available extending into early middle age in the biracial (black-white) population of Bogalusa, Louisiana. Left ventricular mass index was used to illustrate damaging effects on the CV system by both resting BP levels and fluctuations. Long-term BP variability reflecting intermittent and repeated variability was shown to have a greater effect in blacks. The childhood BP response to several stressors was found to be greater in blacks. These observations suggest that, although at rest a greater vagal effect occurs in blacks, they show a greater response when reacting to a stimulus. This, along with aspects such as carbohydrate-insulin metabolism or other biochemical/physiological differences, may account for the greater acceleration of CV atherosclerosis in blacks. The racial contrasts suggest, in part, that effects of lipoproteins may be greater in whites, whereas the effects of excess BP levels and variability of BP and Na(+)-K(+) intake and diet as well as other environmental effects result in more CV damage in blacks. The strong association of hemodynamic measures with anatomic, metabolic, and environmental factors emphasizes the need to begin prevention of risk factors at an early age. Taken together, understanding racial (black-white) contrasts to stress contribute to both prevention and treatment of hypertension, especially for black males.

Hypertension and left ventricular (LV) hypertrophy are both more common in blacks than in whites. The aim of the present study was to test the hypothesis that blood pressure (BP) has a differential effect on the LV geometry types in black versus white asymptomatic young adults. As a part of the Bogalusa Heart Study, echocardiography and cardiovascular risk factor measurements were performed in 780 white and 343 black subjects (aged 24 to 47 years). Four LV geometry types were identified as normal, concentric remodeling, eccentric, and concentric hypertrophy. Compared to the white subjects, the black subjects had a greater prevalence of eccentric (15.7% vs 9.1%, p < 0.001) and concentric (9.3% vs 4.1%, p < 0.001) hypertrophy. On multivariate logistic regression analyses, adjusting for age, gender, body mass index, lipids, and glucose, the black subjects showed a significantly stronger association of LV concentric hypertrophy with BP (systolic BP, odds ratio [OR] 3.74, p < 0.001; diastolic BP, OR 2.86, p < 0.001) than whites (systolic BP, OR 1.50, p = 0.037; and diastolic BP, OR 1.35, p = 0.167), with p values for the race difference of 0.007 for systolic BP and 0.026 for diastolic BP. LV eccentric hypertrophy showed similar trends for the race difference in the ORs; however, the association between eccentric hypertrophy and BP was not significant in the white subjects. With respect to LV concentric remodeling, its association with BP was not significant in either blacks or whites. In conclusion, elevated BP levels have a greater detrimental effect on LV hypertrophy patterns in the black versus white young adults. These findings suggest that blacks might be more susceptible than whites to BP-related adverse cardiac remodeling.

Carotid intima-media thickness (CIMT) progression is predictive of future cardiovascular events in middle-age and older adults. However, information is scant on segment-specific CIMT progression by race (black vs white) and gender and its predictors during short-term follow-up in asymptomatic young adults. B-mode ultrasound images of the far walls of both carotid arteries were obtained in 842 subjects aged 24 to 43 years and enrolled in the Bogalusa Heart Study (70% whites and 42% men). The CIMT and cardiometabolic risk variables were measured at baseline and after an average of 2.4 years. The mean CIMT progression rates/year adjusted for age, race, and gender were greatest at the bulb, followed by the internal and common carotid segments (p

Blood pressure (BP) is a variable physiological parameter in health and disease. Increased BP variability over time in adults is associated with severity of end-organ damage and a higher rate of cardiovascular events, even after adjusting for the mean levels. This study tested the hypothesis that childhood BP variability, besides the mean levels, is also predictive of adulthood hypertension.The study cohort consisted of 1,797 subjects (1,091 whites and 706 blacks; age = 21-48 years) enrolled in the Bogalusa Heart Study since childhood. BP variability was depicted as s.d. of 4-8 serial measurements in childhood.Blacks showed significantly greater childhood systolic BP (SBP) variability than whites. In multivariable logistic regression analyses, adjusting for race, sex, mean childhood age, s.d. of childhood body mass index (BMI), mean childhood BP levels, adulthood age and BMI, adult hypertension was significantly associated with s.d. of childhood SBP (odds ratio (OR) (95% confidence intervals) = 1.28 (1.09, 1.51), P = 0.002) and s.d. of childhood diastolic BP (DBP; 1.36 (1.16, 1.58), P0.001). When using adulthood BP levels as continuous dependent variables in linear regression models, adjusting for the same covariates, adulthood SBP and DBP levels were significantly associated with s.d. of childhood SBP (standardized regression coefficient β = 0.086, P0.001) and s.d. of childhood DBP (β = 0.105, P0.001), respectively.Increases in BP variations as well as levels in early life are predictive of adult hypertension, which underscore the childhood origin of the natural history of essential hypertension.

Background— Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis. Methods and Results— We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61], P =0.0003), 12 years (1.48 [1.28 to 1.72], P P P P =0.42) and 6 years (1.20 [0.96 to 1.51], P =0.13) were weaker and nonsignificant. Conclusions— Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood.

Background: The cutoffs from the Centers for Disease Control and Prevention (CDC) growth charts and from the Cooper Institute (FitnessGram) are widely used to identify children who have a high body mass index (BMI). Objective: We compared the abilities of these 2 systems to identify children who have adverse lipid concentrations and blood pressure measurements and the reliability (consistency) of each classification system over time (mean follow-up: 7 y). Design: A cross-sectional analysis based on data from 22,896 examinations of 5- to 17-y-olds was conducted. Principal components analyses were used to summarize levels of the 5 risk factors, and likelihood ratios and the κ statistic were used to compare the screening abilities of the 2 systems. Of these children, 3972 were included in longitudinal analyses. Results: There were marked differences in the prevalence of a high FitnessGram BMI by age, with the prevalence among boys increasing from 2.5% to 21% between the ages of 5 and 11 y. The identification of adverse risk factors by the 2 systems was only fair (κ = 0.25), but there was little difference in the abilities of the CDC and FitnessGram cutoffs to identify high-risk children. Longitudinal analyses, however, indicated that the agreement between initial and follow-up FitnessGram classifications was substantially lower than that based on CDC cutoffs (κ = 0.28 compared with 0.49). Conclusions: The FitnessGram and CDC cutoffs have similar abilities to identify high-risk children. However, a high FitnessGram BMI is difficult to interpret because the reliability over time is low, and the prevalence increases markedly with age.

Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases. The Framingham risk score (FRS) is widely being used in the early prediction of coronary artery disease (CAD). However, the association between FRS and femoral artery IMT has not been studied in asymptomatic younger black and white adult population. Our objective was to examine the association between FRS and femoral artery IMT in asymptomatic younger adults.Subjects (n=1080; 71% white, 43% male) aged 24-43 years enrolled in the Bogalusa heart study. Femoral IMT was measured by B-mode ultrasonography. Age, gender, systolic blood pressure, diastolic blood pressure, low density lipoprotein cholesterol, high density lipoprotein cholesterol, cigarette smoking and type2 diabetes were used to calculate individual FRS.FRS was lower in females (p=0.001) than males. Age-adjusted femoral IMT showed gender differences (malesfemales, p=0.001) among whites only; and no race difference in both genders. A significant positive linear relationship between tertiles of FRS and IMT of femoral artery was noted in whites and blacks alike (p for trend0.0001). In a multivariate analysis that included FRS, race, body mass index (BMI), log insulin, log triglycerides, exercise and alcohol intake; FRS, insulin and BMI were significantly and independently associated in that order with femoral IMT.The findings support the use of FRS in both white and black younger adults and underscore the importance of prevention and control of FRS variables in youth.

OBJECTIVES Although low birthweight is associated with elevated blood pressure (BP) levels, whether the strength of this relationship is amplified with age is still debated. This study tested the hypothesis that the magnitude of the birthweight-BP association increases with age from childhood to adulthood. METHODS The study cohort included 6251 individuals (64.5% whites and 35.6% blacks, 50.0% males) enrolled in the Bogalusa Heart Study. Individuals were examined 1-15 times for BP from childhood to adulthood, with 24 363 observations. Information on birthweight and gestational age was obtained from Louisiana State birth certificates. RESULTS After adjusting for race, sex, age and gestational age, low birthweight (kg) was associated with higher SBP levels (mmHg) in adolescence (aged 12-17 years, regression coefficient β = -0.80, P = 0.004) and adulthood (aged 18-50 years, β = -1.34, P = 0.010). Adjustment for current BMI yielded considerably stronger association. Importantly, the magnitude of the birthweight-SBP relationship, measured as standardized β(unit = SD), was significantly amplified with increasing age, regardless of adjustment for current BMI and race. Further, the strengthened association (the increase in standardized β ranging 0.02-0.12) by adjustment for current BMI was closely related to the BMI-SBP and birthweight-BMI correlations, especially noted in childhood. CONCLUSION These findings on the potentiating effect of increasing age on the birthweight-BP relationship suggest that the fetal programming and the increasing cumulative burden with age of unhealthy lifestyle behaviors affect the development of adult hypertension in a synergistic manner.

OBJECTIVE:A 2008 report from the American Academy of Pediatrics recommended both population and individual approaches (including pharmacologic interventions) for adolescents who had low-density lipoprotein (LDL) cholesterol levels above various cutoff points (130, 160, and 190 mg/dL). However, the tracking and variability of these very high levels have not been investigated.METHODS:A total of 6827 subjects underwent multiple LDL cholesterol determinations in childhood and adulthood in the Bogalusa Heart Study. The total number of determinations was 26748, and the median interval between examinations was 3 years.RESULTS:Correlations between initial and subsequent LDL cholesterol levels ranged from r ∼ 0.8 for measurements made within the same year to r ∼ 0.5 for periods of ≥20 years. Most children who had very high LDL cholesterol levels, however, had substantially lower levels at the next examination. LDL cholesterol levels between 160 and 189 mg/dL (n = 201) decreased, on average, by 21 mg/dL at the next examination, whereas levels of ≥190 mg/dL (n = 44) decreased by 34 mg/dL. In contrast, the mean increase for LDL cholesterol levels of CONCLUSIONS:There can be large changes in extreme levels of LDL cholesterol because of regression to the mean, and practitioners should be aware that very high levels may decrease substantially in the absence of any intervention.

Telomeres are engaged in a host of cellular functions, and their length is regulated by multiple genes. Telomere shortening, in the course of somatic cell replication, ultimately leads to replicative senescence. In humans, rare mutations in genes that regulate telomere length have been identified in monogenic diseases such as dyskeratosis congenita and idiopathic pulmonary fibrosis, which are associated with shortened leukocyte telomere length (LTL) and increased risk for aplastic anemia. Shortened LTL is observed in a host of aging-related complex genetic diseases and is associated with diminished survival in the elderly. We report results of a genome-wide association study of LTL in a consortium of four observational studies ( n = 3,417 participants with LTL and genome-wide genotyping). SNPs in the regions of the oligonucleotide/oligosaccharide-binding folds containing one gene ( OBFC1 ; rs4387287; P = 3.9 × 10 −9 ) and chemokine (C-X-C motif) receptor 4 gene (CXCR4 ; rs4452212; P = 2.9 × 10 −8 ) were associated with LTL at a genome-wide significance level ( P < 5 × 10 −8 ). We attempted replication of the top SNPs at these loci through de novo genotyping of 1,893 additional individuals and in silico lookup in another observational study ( n = 2,876), and we confirmed the association findings for OBFC1 but not CXCR4 . In addition, we confirmed the telomerase RNA component (TERC) as a gene associated with LTL ( P = 1.1 × 10 −5 ). The identification of OBFC1 through genome-wide association as a locus for interindividual variation in LTL in the general population advances the understanding of telomere biology in humans and may provide insights into aging-related disorders linked to altered LTL dynamics.

Background Low birth weight, an indicator of intrauterine growth restriction, is associated with adult cardiovascular (CV) disease, type 2 diabetes, and adverse levels of CV risk factors. Impaired pulsatile arterial function is also an independent predictor of early vascular damage and related CV outcome. However, information is scant regarding the influence of low birth weight on pulsatile arterial function. Methods The study cohort consisted of 538 black and white subjects (29% black, 42% male) aged 18-44 years (mean 36.7 years) enrolled in the Bogalusa Heart Study. Subjects were categorized into low birth weight and normal birth weight. Pulsatile arterial function was assessed in terms of large artery compliance, small artery compliance, and systemic vascular resistance by noninvasive radial artery pressure pulse contour analysis. Results Blacks and females had significantly lower birth weight compared to their counterparts. Low vs. normal birth weight group had lower large artery compliance (13.3 ml/mm Hg x 10 vs. 15.5 ml/mm Hg x 10, P = 0.0002). Further, after adjusting for age, race, and sex, the large artery compliance increased across quartiles of increasing birth weight specific for race, sex, and gestational age (P for trend = 0.03). In multivariate regression model, adding race, sex, age, body surface area, systolic blood pressure, diastolic blood pressure, triglycerides/high-density lipoprotein cholesterol ratio one by one, the effect was attenuated but significant (beta = -0.067, P = 0.033). Conclusions The observed deleterious association of low birth weight on arterial wall dynamics in asymptomatic younger adults may account in part for the adverse CV risk in the Bogalusa sample.

That circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) is associated with an increased risk for coronary artery disease is well recognized. However, information is scant regarding the distribution and cardiovascular (CV) risk correlates of sICAM-1 in asymptomatic young adults.Plasma sICAM-1 was measured in 1,184 black and white persons in the Bogalusa Heart Study cohort (70% white, 43% male), aged 24 to 44 years. CV risk was assessed in terms of CV risk factors, status of parental CV disease, and composite carotid intima-media thickness (IMT).sICAM-1 levels displayed race difference (whitesblacks, p0.0001), but no sex difference. In multivariate analysis including age, race, sex, smoking status, waist circumference, mean arterial pressure, low- and high-density lipoprotein (LDL and HDL) cholesterols, triglycerides, insulin resistance index, C-reactive protein (CRP), and adiponectin, the significant predictors of sICAM-1, in order of entry, were race (whiteblack), smoking, CRP, and waist circumference. Furthermore, there was a smoking by waist circumference interaction in that smoking attenuated the magnitude of correlation between waist circumference and sICAM-1. Levels of sICAM-1 adjusted for age, race, sex, and smoking increased with number of metabolic syndrome components (p for trend0.01); positive family history of CV disease (p0.05); and increased in composite carotid IMT specific for age, race, and sex (p for trend0.05).These findings underscore the potential value of plasma sICAM-1 as an additional biomarker for CV risk among asymptomatic young adults.

Data on the utility of the waist-to-height ratio in detecting central obesity and related cardiovascular risk among normal weight younger adults are scant. This aspect was examined in 639 normal weight (body mass index 18.5 to 24.9 kg/m(2)) black and white adults (75% white and 36% men) 20 to 44 years old. The subjects with a waist-to-height ratio > or =0.5 were grouped as having central obesity normal weight, with the rest considered the control group. The subjects with central obesity, compared to the controls, after adjusting for age, race, and gender, had significantly greater diastolic blood pressure, mean arterial pressure, low-density lipoprotein cholesterol level, triglycerides, triglycerides/high-density lipoprotein cholesterol ratio, insulin, homeostasis model assessment of insulin resistance, uric acid, C-reactive protein, and liver function enzymes (alanine aminotransferase and gamma-glutamyl transferase). On multivariate analysis, the central obesity group compared to the control group was 1.9, 2.2, 2.9, and 2.5 times more likely to have significantly adverse levels (top tertile vs the rest) of mean arterial pressure, triglycerides/high-density lipoprotein cholesterol ratio, homeostasis model assessment of insulin resistance, and C-reactive protein, respectively. The central obesity group also had a greater prevalence of dyslipidemia, hypertension, insulin resistance, hyperuricemia, and elevated C-reactive protein. The age-, race-, and gender-adjusted mean value of the common carotid intima-media thickness, a measure of subclinical atherosclerosis, was greater in the central obesity group compared to the control group (0.76 vs 0.71 mm, p = 0.009). In conclusion, these findings underscore the utility of the waist-to-height ratio in detecting central obesity and related adverse cardiovascular risk among normal weight younger adults.

Objective This study examined the relationships of high-density lipoprotein cholesterol (HDL-C) with LTL and the rate of its shortening. Background Diminished levels of HDL-C are associated with an increased risk for atherosclerosis. Shortened leukocyte telomere length (LTL) also entails an increased atherosclerotic risk. Methods We studied 472 Whites and 190 African Americans (AfAs) enrolled in the Bogalusa Heart Study. Subjects were examined serially 3–13 times for HDL-C over an average period of 27.8 years from childhood through young adulthood. LTL was measured twice during adulthood at a mean age of 31.5 years (baseline exam) and 37.8 years (follow-up exam). HDL-C trajectories with age were constructed and the area under the curve (AUC) was used as a measure of cumulative HDL-C levels. Results Multivariate regression analyses showed that LTL was positively associated with HDL-C in childhood (regression coefficient (bp per mg/dL) β =3.1, p =0.024), adulthood ( β =4.4, p =0.058) and AUC from childhood to adulthood ( β =12.2, p =0.0004) in the combined sample of AfAs and Whites. The association between LTL and HDL-C AUC was stronger in females ( β =18.5, p β =2.9, p =0.590) (difference in slopes p =0.037). A slower rate of LTL shortening per year was associated with higher HDL-C AUC in the total sample ( p =0.033), adjusting for baseline LTL. Conclusions As HDL-C exerts anti-oxidant and anti-inflammatory effects and LTL registers the accruing burden of oxidative stress and inflammation, the association between HDL-C and LTL might be explained by the lifelong status of oxidative stress and inflammation.

Background: Adverse levels of cardiovascular disease (CVD) risk factors are related to skinfold thicknesses and body mass index (BMI) among children, but the relative strengths of these associations are unknown. Objective: The objective was to determine whether the sum of the triceps and subscapular skinfold thicknesses (SF sum) is more strongly related to levels of 6 risk factors (triglycerides, LDL and HDL cholesterol, insulin, and systolic and diastolic blood pressure) than is BMI. Design: Cross-sectional analyses of schoolchildren examined in the Bogalusa Heart Study from 1981 to 1994 (n = 6866) were conducted. A risk factor summary index was derived by using principal components analysis. Results: After race, sex, study period, and age were controlled for, almost all comparisons indicated that BMI was more strongly related to risk factor levels than was the SF sum. Although the differences were generally small, many were statistically significant. Associations with the risk factor summary, for example, were r = 0.50 for BMI and r = 0.47 for SF sum (P < 0.001 for difference). Furthermore, an adverse risk factor summary was observed among 62% of the children with the highest (upper 5%) BMI levels but among only 54% of children with the highest SF sum levels. Conclusions: BMI is at least as accurate as SF sum in identifying children and adolescents who are at metabolic risk. Because of the training and errors associated with skinfold-thickness measurements, the advantages of BMI should be considered in the design and interpretation of clinical and epidemiologic studies.

The aim of this study was to determine the association between homocysteine and arterial wall stiffness in a biracial (black and white) community-based cohort of asymptomatic young adults. That increased plasma homocysteine was adversely associated with atherothrombosis was well recognized. However, findings about the association of homocysteine and arterial wall stiffness, an indicator of vascular damage, were conflicting. Plasma homocysteine and other cardiovascular disease risk-factor variables were measured in 735 white and 294 black subjects aged 24 to 44 years enrolled in the Bogalusa Heart Study. Large-artery stiffness was assessed in terms of aorta-femoral pulse wave velocity (af-PWV) using echocardiography Doppler. Men versus women had higher fasting homocysteine (8.85 vs 7.32 micromol/L; p0.01), and blacks versus whites had higher af-PWV (5.47 vs 5.24 m/s; p0.01). In bivariate analyses, log-transformed homocysteine significantly correlated with af-PWV (p = 0.0004). In multivariate stepwise regression analyses, systolic blood pressure, age, heart rate, log-homocysteine, log-Homeostasis Model Assessment of Insulin Resistance, and smoking, in that order, were independently and positively associated with af-PWV. In conclusion, plasma homocysteine was an independent correlate of arterial stiffness in asymptomatic black and white young adults and may be a potential marker for cardiovascular disease risk in this age group.

Differences in geometric adaptation of the left ventricle and associated cardiovascular risk may reflect the differential effects of classic risk factors and arterial stiffness on the left ventricle. In the present study, the influence of cardiovascular risk factors and arterial stiffness indexes on left ventricular (LV) geometry types were studied in a large community-based cohort of young adults. As part of the Bogalusa Heart Study, echocardiographic examinations of the heart were performed on 786 black and white adults (age range 24 to 43 years, average 36; 42% men, 70% white). Arterial stiffness indexes of the study cohort included aorta-femoral pulse wave velocity, carotid artery elastic modulus, and arterial compliance using tonometry. Pulse pressure in young adults with concentric LV hypertrophy (47 +/- 11 mm Hg) was significantly higher than in those with eccentric LV hypertrophy (40 +/- 8 mm Hg) and normal geometry (37 +/- 7 mm Hg). Multinomial logistic regression analysis showed that widened pulse pressure, the presence of diabetes mellitus, and increased body mass index were associated with concentric LV hypertrophy compared with normal geometry. Similarly, higher Peterson's and Young's elastic modulus of the carotid arteries and lower large- and small-artery compliance, in addition to increased body mass index, diabetes mellitus, and black race, were associated with concentric LV hypertrophy in young adults. In conclusion these data suggested that concentric LV hypertrophy was associated with widened pulse pressure, increased arterial stiffness, and decreased arterial compliance in young adults.

Background and Purpose— Vascular remodeling as depicted by increases in arterial lumen diameter occurs in response to development of atherosclerosis. However, data on the correlates of arterial lumen diameter in younger adults by race and sex are limited. Methods— The study cohort included 734 white and 306 black subjects, aged 20 to 43 years, enrolled in the Bogalusa Heart Study. The common carotid artery lumen diameter at diastole and intima media thickness (IMT) were measured by M- and B-mode ultrasonography, respectively. Results— As a group, blacks versus whites (3.44 mm/m versus 3.37 mm/m, P =0.002) and males versus females (3.45 mm/m versus 3.35 mm/m, P P =0.011 for mean arterial pressure; P =0.033 for IMT); interaction effects of body mass index and mean arterial pressure with sex on height-adjusted lumen diameter were also noted with males showing steeper slopes (difference in slopes: P =0.003 for body mass index; P =0.005 for mean arterial pressure). In addition, the lumen diameter–carotid IMT relationship was stronger in hypertensives than in normotensives (difference in slopes: P =0.038). Conclusions— Common carotid artery lumen diameter is influenced by carotid artery IMT, adiposity, and blood pressure in a race- and sex-specific manner in asymptomatic younger adults, which may have implications for preventive cardiology.

Objectives This study was designed to determine which of the National Cholesterol Education Program or National Health and Nutrition Examination Survey low- and high-density lipoprotein cholesterol classifications of dyslipidemia status in adolescents is most effective at predicting high common carotid artery intima-media thickness (IMT) in adulthood. Background Two classifications of pediatric dyslipidemia status have been proposed. No study has assessed which of these is most effective for predicting adolescents who will develop preclinical atherosclerosis in adulthood. Methods Three population-based, prospective cohort studies collected lipoprotein measurements on 1,711 adolescents age 12 to 18 years who were remeasured as young adults age 29 to 39 years. Lipoproteins in adolescence were classified according to National Cholesterol Education Program and National Health and Nutrition Examination Survey cut points, and high IMT in adulthood was defined as those at or above the age-, sex-, race-, and cohort-specific 90th percentile of IMT. Results Independent of the classification employed, adolescents with dyslipidemia were at significantly increased risk of having high IMT in adulthood (relative risks from 1.6 to 2.5). Differences in predictive capacity between both classifications were minimal. Overweight or obese adolescents with dyslipidemia had increased carotid IMT (males: 0.11 mm; females: 0.08 mm) in adulthood compared with those who did not have both risk factors. Adolescent dyslipidemia status was more strongly associated with high IMT in adulthood than change in dyslipidemia status. Conclusions Pediatric dyslipidemia classifications perform equally in the prediction of adolescents who are at increased risk of high IMT in young adulthood. Our data suggest that dyslipidemia screening could be limited to overweight or obese adolescents.

Leukocyte telomere length (LTL) is ostensibly a biomarker of human aging. Cross-sectional analyses have found that LTL is relatively short in a host of aging-related diseases. These studies have also provided indirect estimates of age-dependent LTL shortening. In this paper, the authors report findings of the first comprehensive longitudinal study of 450 whites and 185 African Americans in Louisiana (aged 31.4 and 37.4 years at baseline (1995–1996) and follow-up (2001–2006) examinations, respectively) participating in the Bogalusa Heart Study. Rate of change in LTL was highly variable among individuals, with some displaying a paradoxical gain in LTL during the follow-up period. The most striking observation was that age-dependent LTL shortening was proportional to LTL at baseline examination. At both baseline and follow-up examinations, African Americans had longer LTLs than whites, and smokers had shorter LTLs than nonsmokers. The longer LTL in African Americans than in whites explained in part the faster rate of LTL shortening observed among African Americans. These findings underscore the complexity of leukocyte telomere dynamics in vivo and suggest that determinants in addition to the ‘‘end-replication problem’’ contribute to telomere shortening in vivo.