Theda A. Foster

Parental history and cardiovascular disease risk factor variables in children

Abstract As part of a total community study of cardiovascular disease (CVD) risk factor variables in children (ages 5–17 years), parental histories of heart attacks, hypertension, diabetes, and stroke were obtained for each of 4,074 participating children. Subsequently, each child was examined for serum total cholesterol, triglycerides, lipoproteins (LP) and glucose, measurement of height, weight, triceps skinfold thickness, and blood pressure (BP), and had a physical examination. A family history of high BP was reported by 26.5% of all children, diabetes by 7.1%, heart attacks by 6.8%, and stroke by 2.1%. The children of parents with heart attacks or diabetes were heavier and had different lipid and LP profiles than children without this background. Children of reported hypertensive parents had higher systolic and diastolic BP, were heavier and had thicker skinfolds. The heaviest children were more likely to have a parental history of diabetes, hypertension, and heart attack. Children in the highest decile for systolic or diastolic BP were more likely to come from a family reporting hypertension. Children with the highest cholesterol, triglycerides, β + pre-β-LP and lowest α-LP values tended to have parents with heart attacks or diabetes. These data indicate that familial tendencies in multiple CVD risk factors are observable early in life. Children of parents with CVD or manifested risk factors clearly differ in their own risk factor profiles from children of parents without these conditions.

Normolipidemic Subjects With Low HDL Cholesterol Levels Have Altered HDL Subpopulations

Epidemiological studies have established that plasma concentration of HDL is inversely correlated with the risk of coronary heart disease, even in the absence of increased LDL cholesterol levels. We postulate that specific HDL subpopulations may be responsible for antiatherogenic properties of HDL. HDL subpopulations were quantitated by two-dimensional gel electrophoresis in 79 normolipidemic healthy male subjects. To eliminate the influence of diet, volunteers consumed an average American diet for 6 weeks. After the diet period, subjects were stratified according to their HDL cholesterol (HDL-C) levels to low HDL-C < 0.91 mmol/L (< 35 mg/dL), medium > 0.91 < 1.30 mmol/L (> 35 < 50 mg/dL), and high > or = 1.30 mmol/L (> or = 50 mg/dL) groups. Plasma triglycerides and insulin levels were in the normal range, but subjects with low HDL-C levels had higher concentrations of plasma triglycerides and insulin than subjects with medium or high HDL-C concentrations. The absolute concentration (mg/dL) of apoA-I in the largest alpha-migrating HDL subpopulation (alpha 1) was (P < .01) lower in the low HDL-C subjects compared with the medium and high HDL-C groups. The relative concentration (percent distribution) of apoA-I was decreased (P < .01) in alpha 1 and increased (P < .01) in alpha 3 subpopulations. A positive correlation between HDL-C and alpha 1 (P < .001) and a negative correlation between HDL-C and alpha 3 were observed. The inverse correlation of apoA-I distribution (relative concentration) between alpha 1 and alpha 3 suggests an interconversion of alpha 1 and alpha 3 subpopulations, possibly by cholesteryl ester transfer protein. Pre-beta subpopulations showed an inverse trend with HDL-C, while the pre-alpha subpopulation behaved similarly to the alpha-migrating subpopulation. Colocalization of apoA-I and apoA-II particles in the different HDL subpopulations demonstrated that alpha 1, pre-beta 1, and pre-beta 2 subpopulations are apoA-I-only particles rather than apoA-I:A-II particles.

Measurement error of risk factor variables in an epidemiologic study of children-the Bogalusa heart study.

Estimates of measurement error (precision) and of reliability (reproducibility) were obtained from two cross-sectional epidemiologic surveys of cardiovascular risk factor variables. Anthropometric, blood pressure and serum lipid measurements were obtained on children (ages 5–14 yr, N = 3524, first survey; ages 5–17 yr, N = 4074, second survey) in the biracial community of Bogalusa, Louisiana. The measurement error decreased by one half for the serum total cholesterol (from 9.50 to 4.04 mg%) and triglycerides (from 10.34 to 5.05 mg%,) between the two surveys. Although the measurement error remained stable for the automatic height and weight instruments, it decreased for the manual instruments. A decrease in the measurement error between the two surveys was also noted for the triceps skinfold thickness, the upper-arm length and the upper-arm circumference. Concurrent with the decrease in measurement error, there was an increase in reliability. The anthropometric variables were the most reliable, followed by the laboratory and then the blood pressure variables. The reliability during the second survey ranged from 0.99 to 0.9999 for the anthropometric variables, from 0.87 to 0.98 for the laboratory variables and from 0.75 to 0.89 for the blood pressure variables. The increasing reliability may indicate a reduction in the phenomenon of regression to the mean, the effect of training on the examiners, the increased proficiency in the use of the Technicon AAII and an increased capability of tracking variables over time.

Plasma glucose and insulin levels in relation to cardiovascular risk factors in children from a biracial population—The Bogalusa heart study

Abstract In order to describe the natural history of cardiovascular risk factors, we studied 4074 children ages 5–17 yr from an entire geographic population (88% participation, 65% white and 35% black). Fasting plasma glucose, serum lipids and lipoprotein fractions, blood pressure, anthropometric, and other characteristics were measured, and additionally plasma insulin was assayed for 403 children selected randomly. For the plasma glucose and insulin, levels and distributions were compared among the various age, race, and sex groups. Glucose levels initially rose with age and then declined at puberty. We noted a positively skewed distribution for insulin while insulin levels increased with age. In the relationship with cardiovascular risk factors, a positive association was observed for glucose or insulin with body weight, height, obesity indices, serum triglycerides, pre-β-lipoprotein, and inversely with α-lipoprotein levels. All of these variables, however, accounted for only 6–10% of the variation of plasma glucose, but for 16–34% of the variation of plasma insulin. In addition, we found for white boys and girls a positive correlation between systolic blood pressure and plasma glucose, controlling for anthropometric variables and age (Pearson partial correlation coefficient = 0.1, p

Transitions of cardiovascular risk from adolescence to young adulthood—The Bogalusa heart study: I. Effects of alterations in lifestyle

Adolescence and young adulthood represents a transition period for biologic and lifestyle characteristics. In a preliminary investigation of young adults (ages 18-20 years), the Bogalusa Heart Study documented patterns of alcohol, tobacco, and oral contraceptive use, as well as changes in education, occupational, marital and parenting status. Such behaviors accelerate the cardiovascular disease process and may differentially influence risk factor patterns of race and sex groups. Adverse levels of systolic blood pressure and alpha-lipoprotein cholesterol were more frequent in married vs single men; elevated triglyceride levels were more frequent in married vs single whites. However adverse levels of beta- and alpha-lipoprotein cholesterol were more frequent in nonparents than in parents. Cigarette smoking and oral contraceptive use were independently related to elevated beta-lipoprotein cholesterol and decreased alpha-lipoprotein cholesterol levels of young white women. Alcohol consumption was highest among white males, with 32% reporting daily consumption of the equivalent of two or more beers or one mixed drink. Alcohol consumption was negatively correlated with blood pressure in white males and positively correlated with alpha-lipoprotein cholesterol in black males. Since such lifestyle factors are related to physiologic risk factors that result in heart disease and adult cardiovascular morbidity and mortality in the older ages, early targeting during adolescence and young adulthood is important.

Serum lipoprotein levels in children: Epidemiologic and clinical implications

Abstract Serum total cholesterol and lipoprotein cholesterol (LPC) were measured in a standardized laboratory in 3568 fasting children and youths, age 5–17 yr, in a biracial population of a total community. Between ages 11–15 yr, mean serum total cholesterol declined 3 mg/dl per year from 155 mg/dl to 143 mg/dl. Both α-LPC (7 mg/dl) and β-LPC (7 mg/dl) decreased while pre-β-LPC (2 mg/dl) increased during adolescence. Measurement errors, based upon a 10% blind duplicate random subsample, and race-sex adjustment factors, were determined for each lipid. Measurement errors were 4 mg/dl for serum total cholesterol and 6, 5 and 2 mg/dl for serum α-, β- and pre-β-LPC respectively. Measurement errors generally exceeded race-sex adjustment factors. For each fasting child serum total cholesterol was standardized for race, sex and age. Deciles for these total cholesterol relative deviates were determined. Mean total and lipoprotein cholesterol were calculated for each decile for each of the four race-sex groups. Both α-LPC and β-LPC steadily increased as the total cholesterol relative deviates increased, but the rate of increase in β-LPC exceeded that for α-LPC. As percentages of total cholesterol relative deviates. β-LPC greatly increased while α-LPC markedly decreased at higher deciles in all race-sex groups. Percentile tables for each lipid were listed with recommendations for use by clinicians caring for children in daily office practice. Guidelines were suggested for total cholesterol and LPC determinations in clinical practice. Children with a total cholesterol level greater than 185 mg/dl should have lipoproteins determined which will enable judgement for therapeutic decisions. Lipid data and lipoprotein ratios from nine selected white male adolescents in the study were presented and discussed. The results suggested a biologic link between earlier post-mortem studies of premature coronary atherosclerosis in young white male adults and epidemiologic studies of coronary heart disease in older adults. Because of the remarkable changes in lipoprotein patterns during adolescence, young men are appropriate targets for the study of methods for intervention to prevent coronary heart disease.

Distributions of serum lipoproteins in children by repeated measurements

Serum lipids and lipoproteins were measured three times over 6 years in a total-community study of children in Bogalusa, Louisiana. Interrelationships and changes in the distributions of serum lipoprotein cholesterol levels were examined in terms of variability and precision of the laboratory measurements. Although distributions of serum lipoprotein cholesterol variables shifted among the three surveys, precision increased markedly as indicated by a decrease in the coefficient of variation for measurement error for total cholesterol, alpha-lipoprotein cholesterol, and triglycerides between Year 1 and Year 4 and then stabilized. Pre-beta-lipoprotein cholesterol was the most difficult variable to measure. The range and magnitude of correlation coefficients between lipid and lipoprotein variables were very similar. Despite quality controls, efforts to standardize laboratory analyses, and adherence to protocols, fluctuations in distributions of lipids and lipoproteins occurred when the same population was restudied. Long-term studies for coronary artery disease prevention should include laboratory safeguards that help to distinguish modest population changes in serum lipids and lipoproteins from laboratory drift.

Divergent responses of serum lipoproteins to changes in dietary carbohydrate and cholesterol in cynomolgus monkeys

Abstract The metabolic effects of dietary carbohydrates (simple versus complex) on lipogenesis, glucose, and insulin responses are well known, but information is lacking on the effect of carbohydrate types on different serum lipoprotein fractions. We therefore studied the differences in responses of serum lipids, lipoproteins, apoproteins, and plasma glucose and insulin to changes in dietary carbohydrates and cholesterol in 12 male cynomolgus monkeys (Macaca fascicularis). For 6 weeks, each monkey was fed one of four semipurified, high-carbohydrate (76.5% cal) diets that provided sucrose or starch with and without 1 mg/kcal cholesterol. Sucrose diet without added cholesterol resulted in consistently higher serum total cholesterol than with a similar starch diet. In contrast, cholesterol-enriched starch diet caused marked increase in serum total cholesterol when compared to similar sucrose diet. Neither starch nor sucrose diets elicited a VLDL-triglyceride response. Observations on apoB, VLDL- and LDL-cholesterol levels essentially reflected serum total cholesterol changes by diet. Changes in HDL-subfractions to dietary carbohydrates were seen mainly in HDL2, with starch producing lower values than sucrose (p sucrose) and cholesterol effect for HDL2. Neither plasma glucose nor insulin showed any diet-related differences. Thus, a high level of dietary carbohydrate with and without added cholesterol provoked divergent responses of serum lipids and lipoproteins between sucrose and starch. Although reasons for the paradoxical responses are not readily apparent, the experiment provides a useful model for further metabolic studies.

Longitudinal changes of serum lipid and apoB levels in a newborn-infant cohort

Longitudinal changes in serum apoB levels in relation to serum lipid levels were determined in a subset (n = 30) of a newborn-infant cohort selected from infants (n = 440) of Bogalusa, Louisiana who were born between January 1, 1974 and June 30, 1975. Serum total cholesterol, triglycerides, beta + pre-beta-lipoprotein cholesterol and apoB levels were measured at birth, 6 mo, 1 yr, 2 yr, and 3 yr of age. The mean +/- SD, mg/dl, levels of these variables increased dramatically (p less than 0.0005) from birth to 6 mo (Total cholesterol: 65.0 +/- 15.7 versus 136.3 +/- 27.4; triglycerides: 32.9 +/- 18.9 versus 82.3 +/- 28.9; beta + pre-beta-lipoprotein cholesterol: 31.8 +/- 9.1 versus 87.3 +/- 25.7; apoB: 20.8 +/- 5.3 versus 49.0 +/- 13.5). On the other hand, the ratio of apoB to beta + pre-beta-lipoprotein cholesterol at birth was significantly higher than at 6 months of age (0.69 +/- 0.24 versus 0.58 +/- 0.12, p less than 0.0005). None of the variables changed significantly between 6 mo and 3 yr of age except the increase in serum total cholesterol level from yr 2 to yr 3 (142.6 +/- 26.6 versus 156.4 +/- 23,0, p less than 0.01). A high intra-child year to year correlation for serum apoB was noted beginning at 6 mo of age (r = 0.67, p less than 0.0001); while the apoB levels were proportional to beta + pre-beta-lipoprotein cholesterol levels in some children, others had varied levels of apoB in relation to cholesterol carried by this apoprotein. The fact that apoB levels persist beginning at 6 mo of age and that we are beginning to observe interindividual differences in levels of cholesterol carried by this apoprotein may have clinical implications for coronary artery disease.

Subtle Electrocardiographic Changes in Children with High Levels of Blood Pressure

One hundred thirty-four children, aged 8 to 17 years, were studied to evaluate differences in left ventricular (LV) voltages with mid-range and high blood pressure (BP) levels. The children were selected from 1,604 children after a series of replicate measurements of BP over a 4-month period. Ninety children were selected from those whose BP persisted at the upper 10% and 44 whose BP remained at the middle range (between the fiftieth and sixtieth percentiles). Factors influencing the electrocardiographic voltage (i.e., triceps skinfold, weight, age, race and sex) were also analyzed. Children in the upper 10% of BP levels showed larger LV voltages R1 + SV1 + RV4 than did those in the middle range. This difference was strongly influenced by larger voltages shown by white children. Males showed larger voltages than females using the same index. Triceps skinfold, age and BP account for 6 to 14% of the electrocardiographic variability in the high BP group. Thus, subtle voltage differences in children with early elevations of BP levels do occur. The larger ventricular voltages on the electrocardiogram may represent an early sign of increased LV mass, as has been noted by echocardiography.