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Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear., Methods and Results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n  = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events., Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

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., (© Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2014. This work is written by (a) US Government employees(s) and is in the public domain in the US.)

Gender differences in the relationship between central and peripheral blood pressure (BP) are not well described. We sought to investigate gender differences between central systolic blood pressure (cSBP) and peripheral systolic blood pressure (pSBP) in adults in the Bogalusa study population. This study enrolled adults in a cross sectional survey conducted in 2007 to 2010. BP was measured with a standard cuff and Omron applanation tonometer. Data were available from 876 participants. Participants were 57.9% female and 42.1% male (mean age, 43.5 ± 4.4 years). Mean (standard deviation) for cSBP - pSBP was 1.0 (6.9) for males and 7.4 (5.2) for females (P < .001). Augmentation index (AI) was higher in women (men, 70.8 ± 14 vs. women: 85.5 ± 13; P < .01), as well as AI standardized to heart rate (HR) of 75 (AI@75; men, 68.5 ± 13 vs. women, 84.4 ± 11.8; P < .01). Female participants had greater difference between cSBP and pSBP than males. This suggests that, given similar peripheral BP, females might be at higher risk for developing target organ damage. Women in this study had higher AI, which may contribute to the difference found between cSBP and pSBP. These findings may explain why women have more age-related left ventricular hypertrophy, and poorer prognosis following myocardial infarction compared with males., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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.

Objective: The prevalence of obesity among children and adolescents increased by almost threefold from the 1970s to 2000. We examined whether these secular changes in BMI were accompanied by increases in blood pressure levels., Methods: A total of 24,092 examinations were conducted among 11,478 children and adolescents (aged 5-17 years) from 1974 to 1993 in the Bogalusa Heart Study (Louisiana)., Results: The prevalence of obesity increased from 6% to 17% during this period. In contrast, only small changes were observed in levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and neither mean nor high (based on the 90th percentile from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents) levels increased over the 20-year period. Within each race-gender group, mean levels of SBP did not change, whereas mean levels of DBP decreased by 2 mm Hg (P < .001 for trend). Levels of BMI were positively associated with levels of SBP and DBP within each of the 7 examinations, and controlling for BMI (along with other covariates) indicated that only ~60% as many children as expected had high levels of blood pressure in 1993., Conclusions: Our finding that levels of DBP and SBP among children in this large sample did not increase despite the increases that were seen in obesity indicates that changes in blood pressure levels in a population do not necessarily parallel changes in obesity. Additional study of the potential characteristics that have ameliorated the expected increase in high blood pressure could lead to further reductions in risk.

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<0.01). The combination genetic risk score was associated with diastolic blood pressure from age 9 years onward (β=0.68 mm Hg; 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<0.0001) compared with the lowest quintile, independent of a family history of premature hypertension. These findings show that genetic variants are associated with preclinical blood pressure traits in childhood; individuals with several susceptibility alleles have, on average, a 0.5-mm Hg higher blood pressure, and this trajectory continues from childhood to adulthood.

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., (Copyright © 2011. Published by Elsevier Inc.)

Background: 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., Methods: 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., Results: 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), P < 0.001). 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, P < 0.001) and s.d. of childhood DBP (β = 0.105, P < 0.001), respectively., Conclusions: 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.

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: The aim of this study was to examine the association of prehypertension with measures of cardiovascular disease risk in a biracial (black-white) population of young adults., Methods: As part of the Bogalusa Heart Study, echocardiography and carotid ultrasonography were performed along with cardiovascular risk factor measurements in 1379 young adult participants (age range 20-44 years, average 36 years; 43% men, 70% white). Participants were categorized as normotensives (60%), prehypertensives (27%) and hypertensives (13%)., Results: The prevalence of prehypertension was significantly higher among men than women (35 vs. 22%) and among blacks than whites (29 vs. 27%). Compared with normotensives, prehypertensives had a greater adverse cardiovascular risk factor profile. Male sex and BMI equally and significantly contributed to the prehypertension status in both whites [odds ratio (OR) and 95% confidence interval 2.66 (1.88-3.74) and 1.10 (1.07-1.14)] and blacks [OR: 2.56 (1.51-4.33) and 1.05 (1.01-1.09)]. Additionally, prehypertensives compared with normotensives had significantly higher left ventricular (LV) mass index, LV internal diameter, and carotid artery intima-media thickness., Conclusion: The condition of prehypertension in young adults shows men>women and black women>white women, and participants with prehypertension already have adverse profiles of risk factors and indices of subclinical cardiovascular disease. A greater percentage of blacks at a relatively young age fall into the hypertensive category. These findings underscore the need for aggressive management of cardiovascular risk in youth at levels below those considered as hypertension.

That essential hypertension is associated with metabolic syndrome is known. However, information is scant regarding the course of development of adverse levels of blood pressure and other risk variables of metabolic syndrome in youth at risk for developing hypertension. This aspect was studied, retrospectively, in a community-based cohort of normotensive (n=2206), prehypertensive (n=721), and hypertensive (n=328) subjects examined serially during childhood (4 to 11 years), adolescence (12 to 18 years), and adulthood (19 to 42 years). Prehypertensive subjects versus normotensive subjects had significantly higher body mass index and subscapular skinfold, systolic (SBP) and diastolic (DBP) blood pressures, and triglycerides beginning in childhood; higher glucose in adolescence; and higher low-density lipoprotein cholesterol, fasting insulin, and insulin resistance index in adulthood. Hypertensive subjects versus normotensive subjects had higher adiposity measures, SBP and DBP, glucose, and triglycerides beginning in childhood; higher insulin and insulin resistant index in childhood and adulthood; and lower high-density lipoprotein, cholesterol in adulthood. Most of these variables progressed adversely at an increased rate in prehypertensive and hypertensive subjects. In a multivariate analysis, adverse changes in adiposity, SBP, and DBP were independently associated with prehypertensive status; and adverse changes in adiposity, SBP and DBP, insulin resistant index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides with hypertension status. As young adults, prehypertensive and hypertensive subjects showed significantly higher prevalence of obesity, hyperinsulinemia, hyperglycemia, and dyslipidemias. Thus, excess adiposity and blood pressure beginning in childhood and accelerated adverse longitudinal changes in risk variables of metabolic syndrome through young adulthood characterize the early natural history of hypertension.

Cardiovascular (CV) diseases remain the major cause of illness and death in the United States. Adverse CV outcomes are influenced by race/ ethnicity and sex. Race and sex contrasts of CV risk factors become evident early in life and have implications for prevention and medical care. Changes in the CV system in hypertensive disease are mediated by interplay among body fatness, insulin sensitivity, and other factors such as renin-angiotensin system and electrolyte homeostasis. Observations from the Bogalusa Heart Study found higher blood pressure levels in Black children even without obesity, renin as a component of the metabolic/insulin resistance syndrome mainly in Whites, and Black-White differences in electrolyte handling, eg, lower urinary excretion of potassium in Blacks. Understanding divergences in hemodynamic and metabolic parameters for developing hypertensive disease can help improve approaches to beginning prevention at an early age. The use of low doses of antihypertensive medications along with prudent diet and physical activity may be considered for children with elevated blood pressure.

Cigarette smoking, an established cardiovascular (CV) disease risk factor, is known to impair pulsatile arterial function in middle-aged and older adults. However, information is scant in healthy young adults for whom smoking is the only CV risk factor, at current guidelines. Nonsmokers (n = 145) and smokers (n = 142) aged on average 36 years were selected for not having obesity, hypertension, dyslipidemia, diabetes, or clinically manifest CV disease. Pulsatile arterial function was measured in terms of large artery compliance (C1), small artery compliance (C2), and systemic vascular resistance (SVR) by noninvasively recorded radial artery waveforms. Smokers versus nonsmokers had significantly lower measures of adiposity and LDL-cholesterol; and higher systolic blood pressure and triglycerides. In addition, smokers versus nonsmokers had lower C2 (5.09 v 6.63 mL/mm Hg x 100, P = .0009) and higher SVR (1399.0 v 1325.5 dyn . sec . cm(-5), P = .006), after adjustment for race, sex, and age. Decreases in C2 (P for trend = .001) and increases in SVR (P for trend = .01) were noted with increasing years of smoking. Multivariate analysis revealed that duration of smoking was associated adversely with C2 (P = .004), independent of race, sex, age, systolic and diastolic blood pressures, HDL-cholesterol, triglycerides, glucose, and insulin. The odds of having adverse C2 (bottom 10 percentile) and SVR (top 10 percentile) were, respectively, 2.9 (P = .01) and 2.6 (P = .07) times higher in smokers versus nonsmokers. The observed deleterious effects of cigarette smoking on arterial wall dynamics in otherwise healthy young adults underscore the need for aggressive early prevention and intervention strategies to control smoking behavior.

Uric acid has been proposed as an important risk factor in the development of primary hypertension in humans. However, limited information is available linking childhood uric acid levels and blood pressure levels in adulthood. This study examined 334 whites and 243 blacks enrolled in the Bogalusa Heart Study as children aged 5 to 17 years and as adults aged 18 to 35 years. The average follow-up period was 12 years. Childhood uric acid was significantly correlated with childhood and adult blood pressure, both systolic and diastolic. In a multivariate regression analysis, adjusting for age, sex, race, childhood body mass index, childhood uric acid levels, and change in levels of uric acid were significant predictors of adult diastolic blood pressure, whereas change in uric acid was a significant predictor of adult systolic blood pressures. In conclusion, elevated childhood serum uric acid levels are associated with increased blood pressure beginning in childhood and higher blood pressure levels that persist into adulthood, in males and females, whites and blacks, suggesting that early elevations in serum uric acid levels may play a key role in the development of human hypertension.

Impaired endothelial function caused by decreased NO production plays a pathophysiologic role in essential hypertension. Although cross-sectional data are available on the association between endothelial NO synthase gene polymorphisms and hypertension, whether the gene variants and their haplotypes affect the long-term cumulative burden and trend of blood pressure since childhood is not known. This aspect was examined using 4 polymorphisms and a community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45 years who have been examined serially 4 to 13 times (7705 observations) over an on average of 23.4 years. The area under the curve calculated using a growth curve of serial measurements of mean arterial pressure was used as a long-term cumulative burden. Blacks compared with whites displayed significantly lower frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209 versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium in both races. After adjusting for age and body mass index, the 894T and 10T alleles were significantly associated with lower long-term burden of blood pressure since childhood in black females and white females, respectively. With respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10) showed significantly lower long-term burden and trend of blood pressure in white females. In conclusion, the endothelial NO synthase gene influences the long-term burden and trend of blood pressure since childhood in females and may contribute to their predisposition to hypertension.

Background: To assess the awareness of hypertension and dyslipidemia in a semirural population of young adults., Methods: A cohort of 5,707 individuals was surveyed by a questionnaire. The awareness analysis was done on 1,454 subjects screened for cardiovascular risk factors 5 years earlier., Results: Among the respondents (n = 3,699, 65%), the prevalence of hypertension among blacks and whites was 11% and 7.3% (P < 0.0001), respectively; dyslipidemia, 4.7% and 5.8% (P = 0.27). Results from the screening showed a prevalence of 11.4% in blacks versus 6.0% in whites (P < 0.0001) for hypertension; 14.2% versus 17.9% (P = 0.12) for dyslipidemia. Males had a higher prevalence of dyslipidemia than females (24% vs. 12%, P = 0.001). Five years later, among those informed of their hypertension, males were more likely to be aware of their hypertension than females [odds ratio (95% confidence interval) = 5.0 (1.4-17.5)]. Increasing age [1.04 (1.0-1.1)], positive parental history of coronary heart disease [2.6 (1.5-4.3)], and higher education level [2.1 (1.2-33.6)] were associated with the awareness of dyslipidemia. Awareness of the condition increased the proportion of subjects receiving treatment for hypertension, but did not change the proportion receiving treatment for dyslipidemia., Conclusions: These results underscore the need for cardiovascular health education efforts in this population group.

Background: Microalbuminuria is considered as a strong predictor of cardiovascular diseases. However, limited information is available for childhood blood pressure (BP) levels and microalbuminuria in adulthood., Methods: This study examined 2,122 individuals enrolled in the Bogalusa Heart Study as children, aged 5 to 17 years, and as adults, aged 20 to 37 years, with an average follow-up period of 16 years. Microalbuminuria is defined as urinary albumin (in milligrams per liter) to creatinine (mmoles per liter) ratio at or above the 90th percentile specific for age, ethnicity, and sex or urinary albumin levels >/=30 mg/L., Results: As children, African American boys had higher BP than white boys. As adults, African Americans had higher BP and urinary albumin/creatinine ratio than whites. After adjusting for age, sex, and body mass index (BMI), African Americans with microalbuminuria in adulthood by either measure had higher systolic (P =.03) and diastolic (P =.02) BP as adults, and higher diastolic (P <.01) as children than those without this condition. On the other hand, whites showed no such significant association. In a multivariate regression analysis, adjusting for sex, childhood BMI, and age, and current smoking status, childhood BP and rate of change in BP from childhood to adulthood were significant predictors of increased urine albumin excretion in African Americans, but not in whites., Conclusions: Elevated BP beginning in childhood is associated with microalbuminuria in adulthood in African Americans, but not in whites, suggesting that African Americans may be more susceptible than whites to BP-related renal damage.

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.

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Listening to Korotkoff sounds (K-sounds) to determine systolic and diastolic blood pressure (BP) has been the standard for noninvasive BP measurement in medical practices for nearly 100 years. It is the essential tool used for evaluation and assessment of patients with hypertension and risks of cardiovascular diseases (CVD) by physicians and nurses despite limited understanding of the nature of K-sounds. Analyzing cuff oscillometric signals to obtain BP has been the foundation of most digital BP monitors available today. DynaPulse is an oscillometric digital BP monitor that records and analyzes subtle changes of pulse waveforms during the course of a BP measurement while cuff pressure slowly decreases from above systolic to below diastolic. This study compares systolic and diastolic readings obtained by K-sound method following the Bogalusa Heart Study protocol and BP measured by DynaPulse (DP2000A) monitor, in order to better understand the nature and difference between K-sound and oscillometric methods. Analysis of means and differences is applied to BP data collected from 803 subjects examined in the Bogalusa Heart Study. The results indicated: 1) DynaPulse systolic was 9 mm Hg higher (P < .0001) than Phase 1 (K1) systolic, 2) DynaPulse diastolic was 5 mm Hg lower (P < .0001) than Phase 4 (K4), and 3) is less than 1 mm Hg higher than Phase 5 (K5) diastolic (P < .0001), when compared with K-sound auscultatory measurement. Understanding the methods and differences of DynaPulse oscillometric and K-sound BP measurements is important for clinic BP screening and self-BP monitoring, as well as future research to improve hypertension and CVD managements. [Copyright &y& Elsevier]

BackgroundBlood 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.MethodsThe 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.ResultsBlacks 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), P < 0.001). 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, P < 0.001) and s.d. of childhood DBP (β = 0.105, P < 0.001), respectively.ConclusionsIncreases 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.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.176 [ABSTRACT FROM AUTHOR]

BackgroundLow birth weight, an indictor 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.MethodsThe 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.ResultsBlacks 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 × 10 vs. 15.5 ml/mm Hg × 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 (β = −0.067, P = 0.033).ConclusionsThe 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.American Journal of Hypertension 2010; doi:10.1038/ajh.2009.218 [ABSTRACT FROM AUTHOR]

Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis.Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry.Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01).Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further. [ABSTRACT FROM AUTHOR]

Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/ insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention. [ABSTRACT FROM AUTHOR]

Studies the epidemiology of hypertension from childhood to young adulthood in Afro-Americans, whites and Hispanic populations in the United States. Differences in blood pressure levels; Influence of environmental factors in blood pressure levels; Comparison of blood pressure and body mass index.

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of carotid and femoral artery atherosclerotic plaque in a community-based population of asymptomatic African American and white men and women, with an age range of 29 to 51 years, and the potential relations with cardiovascular risk factors. Methods: Between 2007 and 2010, 914 subjects, 58% women and 69% white, who were part of the Bogalusa Heart Study, an ongoing study of a southern biracial community in Bogalusa, Louisiana, were followed up from childhood through adulthood and assessed for plaque formation using ultrasound. Of the total number of subjects, those with a history of cardiovascular/cerebrovascular events were excluded. Results: Plaque prevalence ranged from 8% to 14%, with greater frequency in white men. Plaque formation was also associated with smoking, hypertension, diabetes mellitus, age, and white race, in descending order. Conclusions: In this population, studied sequentially since 1973, the presence of plaque correlated with widely recognized cardiovascular risk factors, although we did not detect significant contributions from either obesity or elevated lipids, including low-density lipoprotein cholesterol. It is possible that interventions, such as diet alteration and statin therapy, may have a positive impact on these potential contributors to plaque formation, and hypertension, diabetes mellitus and smoking remain of great importance. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) dilatation may be an early sign of cardiac decompensation progressing to LV dysfunction. Determinants of LV dilatation in young asymptomatic adults are unknown. Five hundred six asymptomatic subjects (mean age 32 ± 3 years) enrolled in the Bogalusa Heart Study underwent echocardiographic examination. LV dilatation (LV end-diastolic diameter >5.5 cm) as measured by M-mode echocardiography was found in 31 subjects (6%). Subjects with LV dilatation had greater body mass indexes (32 ± 9 vs 27 ± 6 kg/m2, p <0.0001), systolic (119 ± 15 vs 112 ± 12 mm Hg, p = 0.007) and diastolic (79 ± 12 vs 75 ± 9 mm Hg, p = 0.04) blood pressures, and LV mass (230 ± 50 vs 123 ± 39 g, p <0.0001). Age, gender, race, and metabolic parameters (glucose, insulin, and lipoprotein levels) did not differ significantly between the subjects with and without LV dilatation. After correction for age, gender, and race differences, adulthood obesity (body mass index >30 kg/m2) was associated with a threefold odds ratio (2.9, 95% confidence interval 1.4 to 6.1), and hypertension (defined as per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) was also associated with a threefold odds ratio (3.0, 95% confidence interval 1.2 to 7.1) for an increased incidence of LV dilatation. There was an incremental increase in LV end-diastolic dimension depending on the presence of hypertension or obesity, and subjects with obesity and hypertension in adulthood had the greatest degree of LV end-diastolic dimensions. In multiple regression analyses, body mass index in childhood was the only significant predictor of LV dilatation in adulthood (odds ratio 1.47, 95% confidence interval 1.03 to 2.09). In conclusion, obesity beginning in childhood and obesity and hypertension in young adulthood are predictors of LV dilatation in an otherwise healthy young adult population. [Copyright &y& Elsevier]

The Framingham risk score (FRS), developed in a white cohort aged 30–74 years, is increasingly used in the early risk identification for coronary artery disease (CAD). This study examines the relationship between FRS and carotid artery intima-media thickness (IMT), a surrogate marker of coronary atherosclerosis, in black and white individuals aged 20–37 years. Five hundred seventeen young adults (aged 20–37 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study had carotid artery ultrasonography. Age, gender, systolic blood pressure, total cholesterol to HDL cholesterol ratio, cigarette smoking habit, type 2 diabetes, and left ventricular hypertrophy (LVH) were used to calculate FRS. Results indicated a significant, positive linear relationship between tertiles of FRS and IMT of the common, bulb, and internal carotid segments in blacks and whites alike. In a multivariate analysis including FRS, race, BMI, parental history of CAD, stroke, type 2 diabetes, or hypertension, log triglycerides, log insulin, alcohol consumption (ml/week), and regular physical activity, the FRS was independently associated with all three carotid segments. Further, the FRS as a main predictor variable explained relatively more of the variance in the IMT of the carotid bulb (9%) than in the common (5%) or internal (3%) carotid segments. These results support the use of FRS in both white and black young adults and underscore the importance of prevention and control of multiple risk factors in youth. [Copyright &y& Elsevier]

Background: Few studies have examined whether hypertension in pregnancy imposes long-term cardiovascular risk compared to a normal pregnancy. The objective of this study was to examine if previous history of hypertension in pregnancy is a risk for hypertension after pregnancy. Methods: A case-control analysis was performed using the Bogalusa Heart Study database. Cases were defined as women whose systolic blood pressure =140 mmHg or diastolic = 90 mmHg, or having hypertension treatment. Controls were defined as women with normal blood pressure. After exclusions, 604 women (67% white and 33% black, aged 32-44 years) were included for analysis. Univariable and multivariable logistic regression were used to estimate the odds ratio (OR) and 95% confidence interval (CI). Results: The prevalence of hypertension in women was 12.1% (73/604). Hypertensive women had higher proportion of previous history of hypertension in pregnancy (25/73, 34%) than normotensive controls (83/531, 13.7%), with an OR of 2.81 (95% CI: 1.64-4.81). After adjustment for age, race, body mass index and smoking, adjusted OR (aOR) of having previous history of hypertension in pregnancy for developing hypertension later was 1.36 (1.00-3.75). In addition, age, black ethnicity and body mass index were associated with hypertension, with aORs of 1.16 (1.09-1.25), 3.73 (2.13-6.52), and 1.09 (1.05-1.13), respectively. Conclusions: Hypertension in pregnancy may be associated with an increased risk of hypertension in later life. Further studies are needed to separate the effect of pregnancy-induced hypertension and pre-exiting chronic hypertension on the subsequent risk of hypertension later in life. [ABSTRACT FROM AUTHOR]