Tracking and Variability in Childhood Levels of BMI: The Bogalusa Heart Study.

OBJECTIVE: Although the tracking of BMI levels from childhood to adulthood has been examined, there is little information on the within-person variability of BMI. METHODS: Longitudinal data from 11,591 schoolchildren, 3,096 of whom were reexamined as adults, were used to explore the tracking and variability of BMI levels. This article focuses on changes in age-adjusted levels of BMI. RESULTS: There was strong tracking of BMI levels. The correlation of adjusted BMI levels was r = 0.88, and 78% of children with severe obesity at one examination had severe obesity at the next examination (mean interval, 2.7 years). Further, an increase in adjusted BMI from +5 kg/m2 (above the median) to + 10 increased the risk for adult BMI ≥ 40 by 2.7-fold. However, BMI levels among children and adolescents were variable. Over a 9- to 15-month interval, the SD of adjusted BMI change was 0.9 kg/m2 , and 0.7% of children had an absolute change ≥ 3.5. This variability was associated with the interval between examinations and with the initial BMI. CONCLUSIONS: Despite the high degree of tracking of BMI, annual changes of 3.5 kg/m2 or more are plausible. Knowledge of this variability is important when following a child over time.

Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood: International Childhood Cardiovascular Cohort Consortium.

BACKGROUND: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. METHODS: The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model. RESULTS: In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P<0.05). The addition of lipids into the nonlaboratory risk model slightly but significantly improved discrimination in predicting high cIMT compared with nonlaboratory-based risk factors only (C statistics for laboratory-based model 0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95% confidence interval, 0.667-0.731]; P=0.02). CONCLUSIONS: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood.

Tracking of BMI z Scores for Severe Obesity.

BACKGROUND: Although the Centers for Disease Control (CDC) growth charts are widely used in studies of childhood obesity, BMI z scores are known to be inaccurate at values greater than the 97th percentile. METHODS: We used longitudinal data from 6994 children in the Bogalusa Heart Study who were examined multiple times to compare tracking of 3 BMI metrics: BMI-for-sex/age z score (BMIz), BMI expressed as a percentage of the 95th percentile (%BMIp95), and levels of BMI z score that adjust for the compression of very high z scores (adjusted z score [BMIaz]). The later 2 metrics, unlike BMIz, do not have an upper limit. The mean interval between examinations was 2.8 years. We were particularly interested in these metrics among children with obesity or severe obesity (%BMIp95 ≥120%). RESULTS: Although there was little difference in the tracking of the 3 metrics in the overall sample, among 247 children with severe obesity, the correlation of BMIz levels between examinations (r = 0.46) was substantially weaker than those for BMIaz and %BMIp95 (r = 0.65 and 0.61). Age-stratified analyses indicated that the weak tracking of BMIz was particularly evident before the age of 10 years (r = 0.36 vs 0.57 and 0.60). Several children with severe obesity showed BMIz decreases between examinations despite having BMI increases of over 5. CONCLUSIONS: Among children with severe obesity, the tracking of BMIz is weak. This is because of the constraints in converting very high BMIs into z scores based on the CDC growth charts. Rather than using BMIz, it would be preferable to express very high BMIs relative to the CDC 95th percentile or to use BMIaz.

Telomeres and the natural lifespan limit in humans.

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.

Adiposity and Cardiovascular Risk Factor Variables in Childhood Are Associated With Premature Death From Coronary Heart Disease in Adults: The Bogalusa Heart Study.

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.

Birth weight was longitudinally associated with cardiometabolic risk markers in mid-adulthood.

PURPOSE: Birth weight (BW) is associated with risk of cardiovascular (CV) disease. The findings from 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. METHODS: Data 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 and 44 years (n = 2,034) were included. RESULTS: BW is inversely associated with insulin resistance, triglycerides, and total cholesterol (P < .01 for all). For 1-kg decrease in BW, insulin resistance increased by 2.3 units, 95% confidence interval (CI) = 0.7-3.9; triglycerides by 8.7 mg per dL, 95% CI = 4.9-12.4, and total cholesterol by 5.4 mg per dL, 95% CI = 1.8-9.1. The association of body mass with adult blood lipids levels is weaker in persons with low versus normal BW. CONCLUSIONS: The 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.

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.

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.

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

Metabolic Syndrome: Bridging the Gap from Childhood to Adulthood.

Childhood and adolescence are particularly vulnerable periods of life to the effects of cardiometabolic risk and later development of atherosclerosis, hypertension, and diabetes mellitus. Developing countries with limited resources suffer most heavily from the consequences of cardiometabolic risk in children and its future implications to the global health burden. A better understanding of mechanisms leading to cardiometabolic risk in early life may lead to more effective prevention and intervention strategies to reduce metabolic stress in children and later disease. Longitudinal "tracking" studies of cardiometabolic risk in children provide a tremendous global resource to direct prevention strategies for cardiovascular disease. In this review, we will summarize the pathophysiology, existing definitions for cardiometabolic risk components in children. Screening and identifying children and adolescents of high cardiometabolic risk and encouraging them and their families through healthy lifestyle changes should be implemented to as a global public health strategy.

Secondhand smoke exposure is associated with increased carotid artery intima-media thickness: the Bogalusa Heart Study.

BACKGROUND: 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. METHODS: 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. RESULTS: Increased adult composite carotid IMT was significantly associated with SHS exposure (regression coefficient, ß = 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 (ß = 81.2 µm, p = 0.005) and whites (ß = 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 ßs (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 trend<0.001). CONCLUSIONS: 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.

Timing of menarche related to carotid artery intima-media thickness in black and white young adult women: the Bogalusa Heart Study.

PURPOSE: 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. METHODS: 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. RESULTS: 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 (ß = -0.150, P = .01) was observed in black women. CONCLUSIONS: 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.

Genetic association and gene-smoking interaction study of carotid intima-media thickness at five GWAS-indicated genes: the Bogalusa Heart Study.

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.

DCAF4, a novel gene associated with leucocyte telomere length.

BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10(-169) to 3.42×10(-24). CONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.

Tobacco smoking strengthens the association of elevated blood pressure with arterial stiffness: the Bogalusa Heart Study.

OBJECTIVES: The study assessed the hypothesis that smoking strengthens the association of adult arterial stiffness with long-term cumulative burden of blood pressure (BP) from childhood to adulthood. BACKGROUNDS: Tobacco smoking and elevated BPs are important risk factors of vascular stiffness. However, the synergistic effect of these two risk factors is not well established, especially for the long-term burden of elevated BP since childhood. METHODS: The study cohort consisted of 945 adults (661 whites and 284 blacks, aged 24-43 years) who have BP measured 4-15 times since childhood (aged 4-17 years) in Bogalusa, Louisiana. The adult arterial stiffness was measured as aorta-femoral pulse wave velocity (afPWV); the total area under the curve (AUC) and incremental AUC were used as a measure of long-term burden and trends of BP, respectively. RESULTS: Increased adult afPWV was significantly associated with higher adulthood (P < 0.001), total AUC (P < 0.001) and incremental AUC (P < 0.001) values of SBP and DBP, but not with childhood BP, after adjusting for age, race, sex, BMI and heart rate. Furthermore, smoking was a significant predictor of increased adult afPWV and BP levels. In the interaction analyses, the increasing trend of afPWV with increasing adult SBP (P = 0.009) and its incremental AUC (P = 0.007) were significantly greater among the current smokers than among the nonsmokers. DBP showed a similar pattern regarding the smoking-BP interaction on afPWV. CONCLUSION: These results, by showing the synergistic effect of tobacco smoking and long-term BP measures from childhood to adulthood on arterial stiffening process, underscore the importance of undertaking preventive strategies early in life and smoking behavior control.

Uric acid is associated with metabolic syndrome in children and adults in a community: the Bogalusa Heart Study.

BACKGROUND: Elevated serum uric acid (UA) is commonly found in subjects with metabolic syndrome (MetS). This study examined the association of UA with levels of individual MetS components and the degree of their clustering patterns in both children and adults. METHODS: The study sample consisted of 2614 children aged 4-18 years and 2447 adults aged 19-54 years. MetS components included body mass index (BMI), mean arterial pressure (MAP), triglycerides to high-density lipoprotein cholesterol ratio (TG/HDLC), and homeostasis model assessment of insulin resistance (HOMA). Observed/expected (O/E) ratio and intra-class correlation coefficient (ICC) were used as a measure of the degree of clustering of categorical and continuous MetS variables, respectively. RESULTS: UA was positively and significantly associated only with BMI in children but with all four components in adults. The odds ratio for MetS associated with 1 mg/dL increase of UA was 1.74 (p<0.001) in children and 1.92 (p<0.001) in adults. O/E ratios showed a significant, increasing trend with increasing UA quartiles in both children and adults for 3- and 4-variable clusters with p-values for trend <0.001, except for BMI-MAP-TG/HDLC and MAP-TG/HDLC-HOMA clusters in children and MAP-TG/HDLC-HOMA cluster in adults. ICCs of 3 and 4 components increased with increasing UA quartiles in children and adults. CONCLUSIONS: These results indicate that UA may play a role in the development of MetS in both pediatric and adult populations alike, which may aid in the identification and treatment of high risk individuals for MetS and related clinical disorders in early life.

Impact of long-term burden of excessive adiposity and elevated blood pressure from childhood on adulthood left ventricular remodeling patterns: the Bogalusa Heart Study.

BACKGROUND: Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. OBJECTIVES: The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. METHODS: This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. RESULTS: Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. CONCLUSIONS: These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood.

Cigarette smoking exacerbates the adverse effects of age and metabolic syndrome on subclinical atherosclerosis: the Bogalusa Heart Study.

Age and metabolic syndrome are major risk factors for atherosclerosis. However, limited information is available regarding whether cigarette smoking, another major, modifiable risk factor, has synergistic effects with age and metabolic syndrome on subclinical atherosclerosis, particularly in young adults. This aspect was examined in 1,051 adults (747 whites and 304 blacks; aged 24-43 years) from the Bogalusa Heart Study. General linear models were used to examine the effects of cigarette smoking and its interactive effects with age and metabolic syndrome on carotid intima-media thickness (CIMT). After adjusting for age, race, and sex, current smokers had lower BMI (mean ± SE: 27.4 ± 0.4, 29.3 ± 0.5, and 29.9 ± 0.3 kg/m2 in current, former, and never smokers, respectively; p<0.0001) and lower levels of fasting glucose (82.8 ± 0.9, 89.5 ± 2.3, and 87.1 ± 1.1 mg/dL, respectively; p = 0.001) and insulin (10.6 ± 0.4, 14.2 ± 1.0, 13.6 ± 0. 6 µU/ml, respectively; p<0.0001). Despite being lean and having favorable levels of glucose and insulin, current smokers had greater CIMT (0.850 ± 0.012, 0.808 ± 0.011, and 0.801 ± 0.006 mm, respectively; p = 0.0004). Importantly, cigarette smoking showed significant interactions with age and metabolic syndrome on CIMT: Age-related change in CIMT in current smokers was significantly greater (0.013 ± 0.002 mm/year) than in nonsmokers (former and never smokers combined) (0.008 ± 0.001 mm/year) (p for interaction = 0.005); the difference in CIMT between those with and without metabolic syndrome was significantly greater in current smokers (0.154 ± 0.030 mm, p<0.0001) than in nonsmokers (0.031 ± 0.014 mm, p = 0.03) (p for interaction<0.0001). In conclusion, cigarette smoking significantly exacerbates the adverse effects of age and metabolic syndrome on subclinical atherosclerosis in young adults, which underscores the importance of prevention and cessation of cigarette smoking behavior in the young.

Sex and race (black-white) differences in the relationship of childhood risk factors to adulthood arterial stiffness: the Bogalusa Heart Study.

BACKGROUND: Cardiovascular risk factors in childhood are predictive of adulthood arterial stiffness. However, it is unknown whether this relationship varies by race or sex. METHODS: Six hundred and eighty adults aged 24 to 43 had been followed for an average of 26.3 years, from the Bogalusa Heart Study. Brachial to ankle pulse wave velocity (baPWV) measured by an automatic oscillometric technique was used as the outcome variable for arterial stiffness during adulthood. Body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, and systolic blood pressure (SBP), all measured in childhood, were used as predictors. The average values of childhood measurements at multiple time points were used, standardized to age, race, and sex-specific z-scores. RESULTS: In the total sample, childhood SBP was the only significant predictor (P < 0.001) for adult baPWV. Significant interactions between sex and BMI (P = 0.001), between sex and LDL-C (P = 0.035), and between race and HDL-C (P = 0.002) on adult baPWV were identified. Childhood predictors of adult baPWV were BMI (30.9 cm/s reduction in baPWV per standard deviation increase, 95% confidence interval [CI]: -55.0, -6.9 cm/s), LDL-C (30.8 cm/s increase, 95% CI: 2.9, 59.5 cm/s), and HDL-C (46.8 cm/s reduction, 95% CI: -76.2, -17.4 cm/s) in white males; SBP (38.2 cm/s increase, 95% CI: 11.0, 65.4 cm/s) in white females; BMI (71.3 cm/s reduction, 95% CI: -119.9, -22.7 cm/s) in black males; and none in black females. CONCLUSIONS: The associations of childhood cardiovascular risk factors with adult arterial stiffness varied by race and sex.

Differences between the fourth and fifth Korotkoff phases among children and adolescents.

BACKGROUND: The relative importance of the fourth (K4) and fifth (K5) Korotkoff phases as the indicator of diastolic blood pressure (DBP) levels among children remains uncertain. METHODS: In a sample of 11,525 youth aged 5-17, we examined interexaminer differences in these 2 phases and the relation of theses 2 phases to adult blood pressure levels and hypertension. The longitudinal analyses were conducted among 2,156 children who were re-examined after age 25 years. RESULTS: Mean (±SD) levels of DBP were 62 (±9) mm Hg (K4) and 49 (±13) mm Hg (K5). K4 showed less interobserver variability than did K5, and 7% of the children had at least 1 (of 6) K5 value of 0mm Hg. Longitudinal analyses indicated that K4 was more strongly associated with adult blood pressure levels and hypertension. In correlational analyses of subjects who were not using antihypertensive medications in adulthood (n = 1,848), K4 was more strongly associated with the adult DBP level than was K5 (r = 0.22 vs. 0.17; P < 0.01). Analyses of adult hypertension (based on high blood pressure levels or use of antihypertensive medications) indicated that the screening performance of childhood levels of K4 was similar to that of systolic blood pressure and was higher than that of K5, with areas under the receiver operator characteristic curves of 0.63 (systolic blood pressure), 0.63 (K4), and 0.57 (K5). CONCLUSIONS: As compared with K5 levels among children, K4 shows less interobserver variability and is more strongly associated with adult hypertension.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.