Distribution and cardiovascular risk correlates of serum triglycerides in young adults from a biracial community: the Bogalusa Heart Study

Elevated serum triglyceride level is increasingly being recognized as an important indicator of cardiovascular risk. The distribution and correlates of serum triglycerides were examined in a biracial (black-white) community-based sample of 1342 young adults (30% black) aged 20-37 years. Triglyceride levels showed significant race (white>black) and sex (male>female) differences. Black females, despite their relatively increased body fatness, had lowest triglyceride levels. In terms of conjoint trait of dyslipidemia based on the National Cholesterol Education Program cutpoints, 9% of white males displayed high triglyceride (> or =200 mg/dl) in combination with low high-density lipoprotein (HDL)-cholesterol (<35 mg/dl). In comparison, none of the black females fell into this category. Serum triglycerides even at levels between 100 and 150 mg/dl were significantly adversely associated with risk variables of insulin resistance syndrome such as adiposity and visceral fatness measures, HDL-cholesterol, insulin, and systolic blood pressure, especially among whites. Visceral fatness as measured by waist circumference (except black males) and insulin were the major predictors of triglyceride levels. Overall, triglyceride levels above 150 mg/dl were associated with increased risk of hypertension (odds ratio (OR)=1.8, 95% confidence interval (CI)=1.8-3.0), type 2 diabetes (OR=3.1, CI=1.4-6.9), parental history of hypertension (OR=1.3, CI=1.0-1.8) and parental history of type 2 diabetes (OR=1.7, CI=1.2-2.3). Thus, serum triglyceride levels may be valuable in the assessment of cardiovascular risk during young adulthood.     

Temporal relation between blood pressure and serum creatinine in young adults from a biracial community: the Bogalusa Heart Study

It is well recognized that end-stage renal disease (ESRD) is associated with accelerated and malignant hypertension. The association of renal disease and what is considered as normal blood pressure is still not clear. The present study examined the temporal relation between blood pressure and renal function reflected by serum creatinine in a biracial (black-white) community-based population enrolled in the Bogalusa Heart Study. The study included 662 young adults aged 19 to 32 years, (white men, n = 188; white women, n = 289; black men, n = 67; and black women, n = 118) who were followed for an average of 7.4 years. In black men, partial correlation adjusted for age, body mass index, serum glucose, uric acid, and cigarette smoking showed that baseline systolic and diastolic blood pressure are not significantly related to baseline serum creatinine, but significantly related to serum creatinine at follow-up (r = 0.38, P = .008 and r = 0.42, P = .003, respectively). Multivariate regression analysis further showed a significant prediction of serum creatinine at follow-up by baseline systolic and diastolic blood pressure (0.031 mg/dL and 0.037 mg/dL rise in follow-up serum creatinine for every 10 mm Hg increase in systolic (P = .000) and diastolic (P = .001) blood pressure at baseline, but not the other way around. Other race and sex groups did not show such significant temporal relations. We conclude that in young black men, higher blood pressure levels within normal range precede and explain part of the increase in serum creatinine, a measure of decline in renal function. Thus, our results underscore the beneficial effect of maintaining blood pressure levels lower than what is considered as the upper normal limit, particularly in black men.     

Echocardiographic functions and blood pressure levels in children and young adults from a biracial population: the Bogalusa Heart Study

M-mode echocardiograms were obtained on 651 healthy subjects, 7-22 years of age, whose diastolic blood pressure levels remained in the same height-, race-, and sex-specific decile during two biannual examinations. Echocardiographic measures of heart size and dynamics were compared across the total blood pressure distribution. Left ventricular stroke volume, cardiac output and ejection fraction, minor axis shortening, velocity of circumferential fiber shortening, and peripheral vascular resistance were correlated with blood pressure levels. There were positive correlations (p less than .001) of cardiac output and stroke volume with both systolic and diastolic blood pressure levels. Left ventricular output and stroke volume were associated with measures of body size, especially height, weight, ponderal index, and body surface area (p less than .001). The left ventricular output and stroke volume increased with age and with systolic blood pressure quintiles in the four race-sex groups. With adjustment for systolic blood pressure and measures of body size, white males had greater cardiac output (1.25 l/minute for ages 18-22 years, p = .01) and stroke volume than black males. Black males had higher peripheral resistance (4.5 mm Hg/(l/minute), p = .01) than whites. These results suggest that different hemodynamic mechanisms operate in the early phase of hypertension in blacks vs. whites in this population.     

Bogalusa Heart Study: a long-term community study of a rural biracial (Black/White) population

The Bogalusa Heart Study, a long-term population study with a continued relationship with a community, addresses the problem of capacity building in minority health research. The study was originally funded as a Specialized Center of Research-Arteriosclerosis (SCOR-A) by the National Heart Lung and Blood Institute (NHLBI). These centers were to conduct research on atherosclerosis, coronary artery disease (CAD), hypertension, diabetes mellitus, and complications of cardiovascular-renal disease as the major causes of deaths in the United States. From earlier research on atherosclerosis, we became interested in the underlying characteristics in early life that would eventually lead to clinical morbidity and mortality from heart disease. An observation at autopsy showed the degree of atherosclerotic involvement in human aortas, from young to older individuals (Figure 1). For example, at age 40 years, marked individual variability occurred in the severity and involvement with atherosclerotic disease. Some individuals showed very little disease, while almost 70% of the surface was diseased in others. Further studies on arterial wall matrix showed aortas from young individuals varied with the extent of disease and its chemical composition. This background stimulated an interest in studying children for early clinical evidence of major adult heart diseases. The Bogalusa Heart Study was begun in 1972 as an epidemiology study of cardiovascular risk factors in children and adolescents; it eventually evolved into observations of young adults. Bogalusa, LA, is a biracial (black/white) rural community 70 miles north of New Orleans, comparable to many other communities in southeastern United States.     

Serum apolipoprotein E in children and adolescents: the Bogalusa Heart Study

Serum apolipoprotein (apo) E levels and its relationship to lipids and lipoprotein cholesterol fractions were examined in a random subsample (n = 561) of children and adolescents (7 to 17 years of age) from a total biracial community. Mean (+/- SD) levels of apo E were higher in blacks (males 4.8 +/- 1.8 mg/dL; females 5.2 +/- 1.8 mg/dL) than in whites (males 3.9 +/- 1.2 mg/dL; females 4.3 +/- 1.0 mg/dL) irrespective of sex (P less than .001). The black-white difference in apo E persisted after controlling for the covariates: sexual maturation, age, adiposity, cigarette smoking, alcohol use, and oral contraceptive use (P less than .001). A sex differential (females greater than males, P less than .01) for apo E was seen in both racial groups. Apo E levels were inversely associated with age (P less than .01) and sexual maturation (P less than .05) only in white males. Apo E related positively and significantly to total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol fractions (HDL2-C and HDL3-C) in certain race-sex groups. Race, HDL2-C, triglycerides (very-low density lipoprotein cholesterol), HDL3-C, and sex were identified as predictor variables for apo E, in that order, and accounted for 21% of its variability in serum. It is conceivable that the observed race-sex differences in apo E may be related to apo E-HDL subfraction, which is thought to participate in the reverse cholesterol transport.     

Q192R polymorphism of the paraoxanase 1 gene and its association with serum lipoprotein variables and carotid artery intima-media thickness in young adults from a biracial community. The Bogalusa Heart Study

Paraoxanase (PON 1), a high-density lipoprotein-associated enzyme, exerts an antiatherogenic effect by protecting low-density lipoproteins (LDL) against oxidation. A common polymorphism at codon 192(Q/R) of the PON 1 gene has been shown to be associated with an adverse lipoprotein profile and increased coronary artery disease (CAD) risk. However, these observations are based mostly on case-control studies involving relatively older adults. This study examined the frequency and phenotypic (lipoprotein variables) effect of the Q192R variant in a community-based sample of 1786 black and white young adults (mean age: 32.5 years; 69% white, 44% males). In addition, the genotypic effect of this polymorphism on ultrasonographically measured carotid artery intima-media thickness (IMT), a surrogate measure of CAD risk, was examined in a subsample of 436 young adults (mean age: 32.6 years; 70% white, 42% male). The frequency of the variant allele (R192) was higher in blacks than in whites (0.668 versus 0.297, P <0.001). After adjusting for age, sex, body mass index, and smoking status, the R versus Q allele was associated with increased HDL cholesterol in whites (P=0.041), whereas the opposite was true in blacks (P=0.008). Neither the Q nor the R allele was associated with LDL cholesterol and triglycerides in both races. The genotypic effect on the carotid IMT adjusted for the covariates including lipoprotein variables was not apparent in whites or blacks. However, among whites, the carotid IMT was lower in carriers (QR + R) versus non-carriers (QQ) of the variant allele among females (P=0.008) and non-smokers (P=0.026). In addition, the variant allele negated the adverse positive relationship between the carotid IMT and triglycerides among whites (P=0.212 for carriers versus P <0.001 for non-carriers). These results indicate a differential effect of the Q192R variant on HDL cholesterol in whites versus blacks and a beneficial interaction effect of the variant allele with individual's sex, smoking status or triglyceride levels on the carotid IMT among whites.     

Black-white differences in cholesterol levels of serum high-density lipoprotein subclasses among children: the Bogalusa Heart Study

Cholesterol levels of serum high-density lipoprotein (HDL) subclasses, HDL2 and HDL3, were examined in a random subsample (n = 561) of children (7 to 17 years of age) from a total biracial community. Overall, black children in younger (7 to 10 years) and older (11 to 17 years) age groups alike had significantly higher HDL2 cholesterol (HDL2-C) and HDL3-C than their white counterparts. In addition, black children had a relatively higher frequency of joint occurrence of high levels of both HDL2-C and HDL3-C. A significant sex-related difference, with girls showing higher values than boys, was noted among younger age groups for HDL2-C. A male-female crossover trend in HDL2-C levels was apparent only among white children, with girls showing higher values after age 11. Both age and sexual maturation were inversely associated with HDL3-C levels in white children, irrespective of sex (p less than .001). Serum triglycerides were inversely related to both HDL2-C and HDL3-C only in white children (p less than .001). A black-white difference in HDL2-C persisted only among boys and girls in the older age group after adjusting for the covariates (sexual maturation, age, adiposity, oral contraceptive use, cigarette smoking, alcohol use, and serum triglycerides). With respect to HDL3-C, the covariate-adjusted difference remained significant only among boys in the older age group. Metabolic variations between the races in response to both physiologic and environmental factors likely account for the divergence in antiatherogenic HDL pattern.     

High density lipoprotein and coronary artery disease risk factors in children with different lipoprotein profiles: Bogalusa Heart Study

Serum high density lipoprotein-cholesterol (HDL-C) and apoprotein A-1 (apo A-1) profiles were examined in subgroups of children (n = 338), initially aged 2-14 years, whose earlier beta-lipoprotein cholesterol (beta-LPC) and pre-beta-lipoprotein cholesterol (pre-beta-LPC) measurements were in extreme percentiles of values from a biracial community. Relationships of HDL-C and apo A-1 to serum lipoprotein lipids, apoprotein B (apo B), subscapular skinfold thickness, fasting and 1/2 hr postglucose plasma insulin, and fasting and 1 hr postglucose plasma glucose and free fatty acids were examined. Clustering of several coronary artery disease risk factors in these children was observed. HDL-C levels tended to be low in children having high pre-beta-LPC levels and apo A-1 levels were low in boys having high pre-beta-LPC levels. Within beta- and pre-beta-LPC strata, differences were also observed with respect to race, but not sex, in the mean levels of both HDL-C and apo A-1. HDL-C and apo A.1 were related inversely to subscapular skinfold thickness and plasma insulin levels in all children except those with low levels of both beta-LPC and pre-beta-LPC. Ratios of low density lipoprotein-cholesterol/HDL-C and of apo B/apo A-1 were related positively with other coronary artery disease risk factors except in children having low levels of both beta-LPC and pre-beta-LPC. The magnitude of these associations was greater in whites than in blacks. These observations may help to identify, at an early age, children at high risk of developing coronary artery disease in adulthood.     

Pressure–heart rate product changes from childhood to adulthood in a biracial population — a crossover phenomenon: the Bogalusa Heart Study

Cardiovascular (CV) hemodynamic characteristics are major risk factors for heart disease. Cross-sectional surveys of 5,976 individuals (47% males; 63% Whites), aged 4 to 44 years, and a subset of 1,365 individuals examined both in childhood and in adulthood were examined for blood pressure and heart rate along with cardiovascular risk factors. In early childhood, Whites showed significantly faster heart rate than Blacks; at adolescence, blood pressure levels became greater in Blacks. The systolic blood pressure times heart rate, the double product, in childhood (Whites > Blacks) is reversed in adulthood (Blacks > Whites). A “crossover” at the young adult age occurs. The crossover was observed at around 20 years in females and 25 years in males. Multivariate analyses indicated age, race, and homeostasis model of insulin resistance were independently related to the double product. Further, there was a significant interaction between age and race. These hemodynamic parameters change with increasing age with a crossover pattern of the pressure-rate product between the different races in young adults. Changes in the double product suggest a greater sympathetic nervous system activation occurring in Blacks reaching adulthood. Although not measured, central vs. peripheral sympathetic–parasympathetic balance, which determine hemodynamic characteristics, is influenced by increasing obesity and carbohydrate-insulin metabolic changes in adulthood. Further, hemodynamic parameters create a cardiovascular burden over time producing subtle, subclinical disease of the cardiovascular system. Control of obesity in the population remains critical.     

Polymorphism in the 5'-flanking region of the insulin gene and its potential relation to cardiovascular disease risk: observations in a biracial community. The Bogalusa Heart Study

The gene frequencies of a polymorphism in the 5'-flanking region of the insulin gene and its relationship to cardiovascular disease risk were studied in a well defined population of children (mean age 5.5 years) from a biracial community. The BglII endonuclease was used for digestion of the DNA around this polymorphic region. The risk factors studied included parental and grandparental self-reported histories of myocardial infarction and diabetes mellitus, fasting glucose and insulin levels, lipoprotein, cholesterol, and triglyceride levels, and skinfold thicknesses and weight. Four alleles were observed at this locus, with the class 2 allele being significantly more common among blacks than whites. Among white children, the class 3 allele was associated with increased risk for grandparental diabetes mellitus. White children with 2 copies of the class 3 allele had significantly higher levels of glucose. Black children with a copy of the class 3 allele had significantly higher levels of insulin. This study indicates that the class 3 allele is potentially associated with risk for diabetes mellitus and coronary heart disease that can be observed in childhood.     

Longitudinal serum lipoprotein changes in white males during adolescence: the Bogalusa Heart Study

Determinants of follow-up levels of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the ratio of LDL-C to HDL-C were analyzed in a longitudinal study. White boys (n = 81) aged 11 to 12 years, when examined in 1973-1974 (year 1) were reexamined in 1978-1979 (year 6) at ages 16 to 17 years. During follow-up, mean levels of LDL-C increased from 87.6 mg/dL to 89.8 mg/dL, mean levels of HDL-C decreased from 67.0 mg/dL to 48.4 mg/dL and the mean LDL-C/HDL-C ratio increased from 1.45 to 2.12. Cross-sectional associations between the serum lipoproteins and weight, triceps skinfold thickness, and ponderosity (wt/ht3) were stronger in year 6 than in year 1. A persistence of ranks was observed between year 1 and year 6 for LDL-C (r = 0.61), HDL-C (r = 0.51), and LDL-C/HDL-C (r = 0.50). Multiple linear regression indicated that year 6 LDL-C levels were positively related to year 1 LDL-C, year 1 Tanner stage (an indication of sexual maturation), and the change in skinfold thickness during follow-up. Follow-up LDL-C/HDL-C was related both to change in height (negatively) and to change in weight (positively), after controlling for year 1 LDL-C/HDL-C. These longitudinal findings were similar to those obtained from earlier cross-sectional analyses and were further verified on an independent cohort of white boys also followed for five years (1976-1977 through 1981-1982).(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between very-low-density lipoprotein lipid and measures of carbohydrate metabolism in children with different lipoprotein profiles: Bogalusa Heart Study

The relationship of VLDL lipid (cholesterol and triglycerides) levels to fasting and postglucose plasma glucose, plasma glucose, insulin, and free fatty acid (FFA) levels were examined in four subgroups of children (n = 311, ages 6 to 18 years) from a total biracial population whose earlier beta- or pre-beta-lipoprotein cholesterol levels (or both) were in the extreme quintiles or quartiles. High beta-lipoprotein cholesterol strata with or without elevated pre-beta-lipoprotein cholesterol showed significantly high levels of FFA and glucose response (mean, 30 and 60 minutes) to oral glucose load, whereas postglucose insulin responses were markedly higher in the high pre-beta-lipoprotein cholesterol strata. VLDL triglycerides related closely with fasting plasma glucose levels (r = 0.53 to 0.60, P less than 0.001) and to a lesser extent with postglucose plasma glucose response (r = 0.37 to 0.44, P less than 0.001) in all cases. For insulin and FFA, however, correlations were significant only in certain subgroups. Similar relationships were noted for VLDL cholesterol. Measurements relating to carbohydrate tolerance, age, and race accounted for 35% to 48% of the variability in VLDL lipid values. Surprisingly, fasting plasma glucose showed the highest partial regression coefficient for VLDL lipid in all subgroups except high pre-beta-lipoprotein cholesterol and low beta-lipoprotein cholesterol category, in which age was the major predictor variable. These results demonstrate that subtle abnormalities in the above-mentioned metabolic interrelationships are established early in life.     

Blood pressure and echocardiographic measures in children: the Bogalusa Heart Study

M mode echocardiograms were obtained from 654 healthy subjects, 7 to 22 years of age, whose diastolic blood pressure levels remained in the same height-, race-, and sex-specific decile during two biannual examinations. Echocardiographic measures of heart size, obtained according to the recommendations of the American Society for Echocardiography, were compared across the entire systolic and diastolic blood pressure distributions. Echocardiographic indexes of left heart size varied as a function of both blood pressure levels and body size. Significant positive correlations were present between systolic blood pressure and different measures of left ventricular size. Left ventricular wall thickness in systole correlated with systolic blood pressure (r = .42, p less than .0001), and persistence of this relationship was noted after adjustment for body size. Left ventricular wall thickness in diastole correlated with blood pressure before adjustment (r = .31, p less than .0001), but the relationship was not significant after adjustment for body size. The ratio of left ventricular thickness to chamber size (systole) correlated with systolic blood pressure levels both before and after adjustment for body size (r = .20 and r = .22, p less than .001). Male subjects of both races demonstrated significantly higher adjusted left ventricular mass, left ventricular wall thickness, and left ventricular chamber size. Adjusted left ventricular wall stress was significantly related to both systolic (r = .14) and diastolic blood pressure levels (r = .14, p less than .001). Measures of left ventricular wall thickness increased throughout the entire blood pressure distribution, indicating a consistent trend rather than a threshold effect seen only in the highest blood pressure groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of carbohydrate intolerance to serum lipoprotein profiles in childhood. The Bogalusa Heart Study

Three hundred-eighty-eight children were selected from a total community and biracial (black-white) population for a special in-depth study related to serum lipoproteins and carbohydrate metabolism. Based on two previous serum lipoprotein determinations of high and/or low beta and pre-beta-lipoprotein cholesterol, they were stratified into four groups. A glucose tolerance test was performed for fasting, 30-minute, and one-hour glucose, insulin, free fatty acids, calcium, and magnesium. Observations of height, weight, and triceps skinfold were also obtained on the children. Children in the high beta-lipoprotein cholesterol groups tended to have higher glucose levels and were more obese than the other groups, while children in the high pre-beta-lipoprotein cholesterol group tended to have high insulin levels following the glucose load. Fasting blood levels were not appreciably different in the various groups, but after the glucose load an unusually high insulin secretory response occurred in black children, especially black girls. Black girls also demonstrated somewhat lower blood sugars than the other race-sex groups. The insulin/glucose ratios were dramatically different in the black children, especially black girls. These differences were particularly noted in the groups with the high pre-beta-lipoprotein. Black children also tended to have higher insulin/free fatty acid ratios during the glucose tolerance test. These differences persisted even after adjusting for obesity. Although not significant, calcium levels consistently decreased in all groups following a glucose load. The observation of racial contrasts in glucose and insulin responses are interesting. While black girls appear to show low glucose and high insulin responses to a glucose load, low and delayed insulin response along with high glucose response occur in whites, especially white girls. Since white children have greater body fat content, these observations suggest more insulin resistance in white children. Even at low levels of obesity, subtle carbohydrate lipid metabolic aberrations are found in children having high levels of serum lipoproteins. A persistence of these conditions could contribute to accelerated atherosclerosis and subsequent coronary artery disease.     

Distribution and metabolic syndrome correlates of plasma C-reactive protein in biracial (black-white) younger adults: the Bogalusa Heart Study

The association between plasma C-reactive protein (CRP), a marker of systemic inflammation, and the metabolic syndrome is well recognized. However, information is scant regarding the component of metabolic syndrome that is critical in modulating CRP levels in younger adults. This aspect was examined in a biracial (black-white) community-based sample of 1083 younger adults (mean age, 36.1 years; 71% white, 45% male) enrolled in the Bogalusa Heart Study. Plasma CRP along with metabolic syndrome variables were measured. CRP levels showed a significant race (black>white, P=.01) and sex (female>male, P=.0001) differences, and related to measures of obesity (body mass index [BMI], waist circumference, and sagittal diameter), blood pressure (systolic, diastolic, and mean arterial blood pressure), lipoproteins (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, total cholesterol-high-density lipoprotein cholesterol ratio), glucose homeostasis (insulin, glucose, homeostasis model assessment of insulin resistance), and uric acid, after adjusting for age, race, sex, and cigarette smoking. Furthermore, CRP levels increased with increasing number of metabolic syndrome risk factors, as defined by the National Cholesterol Education Program Adult Treatment Panel III, regardless of race and sex (P for trend<0001). In multivariate analysis, using 3 separate models for different obesity measures, obesity was the major contributor to the explained variance in each model with BMI, waist, and sagittal diameter contributing 17.0%, 13.4%, and 17.1% of the variance, respectively. In contrast, homeostasis model assessment of insulin resistance contributed 1.2%, 0.3%, and 0% to the explained variance in the models with BMI, waist, and sagittal diameter, respectively. In conclusion, CRP levels differ among race and sex groups and correlate to metabolic syndrome variables in younger adults. In addition, these findings strongly suggest that although obesity and insulin resistance are the main underlying features of the metabolic syndrome, the former appears to be the major mediator of CRP levels, which has important health implications.     

Racial (black-white) differences in serum lipoprotein (a) distribution and its relation to parental myocardial infarction in children. Bogalusa Heart Study.

BACKGROUND. The value of lipoprotein (a) [Lp(a)] in the prediction of coronary artery disease risk very early in life remains to be established in different racial groups. METHODS AND RESULTS. Serum Lp(a) distribution and its relation to parental histories of myocardial infarction were examined in 2,438 children (8-17 years old) from a biracial community. Parental myocardial infarction was used as a surrogate measure of future risk of disease in the offspring. Lp(a) levels averaged 1.7-fold higher in blacks than in whites (p less than 0.0001). A small but significant sex difference (females greater than males, p less than 0.05) was seen in both races. Race was the only independent variable that contributed appreciably (9%) to the variability of Lp(a) in serum. White children with parental myocardial infarction (n = 90) had increased levels of Lp(a) compared with those without parental myocardial infarction (22.4 versus 17.1 mg/dl, p less than 0.01). Furthermore, among white children, the prevalence of parental myocardial infarction was higher in those with Lp(a) levels of more than 25 mg/dl than in those with values of 25 mg/dl or less (9.5% versus 5.4%, p less than 0.01). In contrast, the relation of Lp(a) to parental myocardial infarction was not seen in black children. No associations were observed between parental myocardial infarction and serum levels of any of the lipids or lipoprotein cholesterol classes in children of either race. CONCLUSIONS. Serum Lp(a) levels may prove valuable in the assessment of coronary artery disease risk early in life among white populations. These findings also emphasize the need to evaluate the atherogenic potential of Lp(a) in different racial groups.     

Serum metabolites associate with lipid phenotypes among Bogalusa Heart Study participants

Background and aimsDyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics.Methods and resultsUntargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance.Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10⁻⁵, and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10⁻³, in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses.ConclusionThe current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels.     

Persistence of high diastolic blood pressure in thin children. The Bogalusa Heart Study

Relationships between initial anthropometric variables and subsequent diastolic blood pressure (fourth phase) were examined in children identified as being in the upper quintile for diastolic blood pressure at Year 1. Of 156 white children, aged 10 to 14 years, with diastolic blood pressure levels in the upper age-race-sex-specific quintile at Year 1, 38% remained in the upper quintile at Year 4. However, there was a definite trend for leaner children, defined by ponderosity (weight/height3) to remain in the highest diastolic blood pressure quintile (p less than 0.001). Of white children originally identified in the highest quintile for diastolic blood pressure and the lowest quintile for ponderosity (lean group), 67% (18 of 27) remained in the upper quintile at Year 4. In contrast, only 21% (11 of 52) of white children identified as being in the highest quintile for both diastolic blood pressure and ponderosity (obese group) at Year 1 were in the upper diastolic blood pressure quintile at Year 4. Similar results were seen in children examined 5 years later. Pearson correlation coefficients and linear regression analyses confirmed the negative relationship between initial ponderosity and subsequent diastolic blood pressure, especially in older children. A similar relationship was noted in black children. Potential differences in the etiological process of obesity-related and non-obesity-related high blood pressure were examined. These observations indicate that characteristics other than obesity can contribute to high blood pressure in late childhood.     

Influence of apolipoprotein E polymorphism on serum lipids and lipoprotein changes from childhood to adulthood: the Bogalusa Heart Study

The influence of apolipoprotein (apo) E polymorphism on serum lipoproteins from childhood to adulthood was examined in 1520 individuals, aged 5-14 years at baseline, followed over a 16-year period. At both times, the e2 allele associated with lower LDL cholesterol (P < 0.001) and higher HDL cholesterol (P < 0.05-0.01), the e4 allele with higher LDL cholesterol (P < 0.001). The e2 allele lowered the adulthood LDL cholesterol level to a greater extent than the childhood level (P < 0.05). With respect to tracking, at the lowest quartile of LDL cholesterol distribution, the persistence in ranks over time was higher in the apoE2 group with E2/3 and E2/2 phenotypes compared with the apoE3 group with E3/3 phenotype and the apoE4 group with E3/4 and E4/4 phenotypes (P = 0.001). Longitudinal increases in the ponderal index (weight/height3) lowered the adulthood HDL cholesterol to a larger extent in e2 carriers (P = 0.017). The interindividual variability in LDL cholesterol due to childhood and adulthood ponderal index was 1.8- to 2.3-fold greater in the apoE2 group versus the apoE3 group. Likewise, cigarette smoking, alcohol use and oral contraceptive use in adulthood explained greater variability in triglycerides (5.3-fold), VLDL cholesterol (7.8-fold) and HDL cholesterol (2.9-fold) in the apoE2 group versus the apoE3 group. Thus, the apoE locus influences not only the levels and tracking of certain lipoproteins from childhood to adulthood but also modulates the association between lifestyle-related factors and lipoproteins.