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Abstract 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 0.9135 1 ) was ( P P 1 and increased ( P 3 subpopulations. A positive correlation between HDL-C and α 1 ( P 3 were observed. The inverse correlation of apoA-I distribution (relative concentration) between α 1 and α 3 suggests an interconversion of α 1 and α 3 subpopulations, possibly by cholesteryl ester transfer protein. Pre-β subpopulations showed an inverse trend with HDL-C, while the pre-α subpopulation behaved similarly to the α-migrating subpopulation. Colocalization of apoA-I and apoA-II particles in the different HDL subpopulations demonstrated that α 1 , pre-β 1 , and pre-β 2 subpopulations are apoA-I–only particles rather than apoA-I:A-II particles.

Exposures to toluene diisocyanate (TDI) were studied for effects on respiratory health of workers in two plants manufacturing polyurethane foams. Intensive personal monitoring was used to characterize job exposures. Of 4,845 12-min personal samples, 9% exceeded 5 ppb and 1% exceeded 20 ppb. Initial questionnaire and spirometry were obtained in 386 workers (88.7% of target population). Current smoking was associated with lower mean FEV1 and FEF25-75, but percent predicted (% pred) means were normal in all smoking categories. Multiple regression showed significant adverse effects of cumulative TDI exposure on initial level of FVC and FEV1 of current smokers, and an effect at borderline significance (p less than 0.063) on FEF25-75 over all smoking categories. Logistic regression showed that chronic bronchitis was more prevalent among those with higher cumulative exposures, after controlling for smoking, age, and sex. Methacholine (MCh) reactivity was associated with reduced airway function, -8.5% pred for FEV1 and -20.0% pred for FEF25-75. In 227 with adequate follow-up, the slopes of annual change were abnormal, for example, FEV1 of -67 ml/yr in current and -53 ml/yr in never smokers. Men had worse FEV1 declines than did women, -71 ml/yr versus -43 ml/yr. TDI exposure, lifetime or concurrent, had no significant effect on slopes, despite its demonstrated effects on initial level of lung function and on prevalence of chronic bronchitis.

Background: When developing a new laboratory test for study of human diseases, it is important to identify and control internal and external sources of variation that affect test results. It is also imperative that the precision of the test not only meets pre-established requirements and not exceed allowable total error, but also that these objectives are reached without undue expenditure of either time or financial resources. Methods: This study applies statistical principles in designing a cost-effective experimental approach for determining the analytical precision of a new test. This approach applies the statistical concept of variance components to the problem of balancing a pre-established level of analytical precision against expenses incurred in achieving this precision. Results: We demonstrated (1) estimation of variance components, (2) use of these estimates for improving allocation of costs within the experiment, and (3) use of these estimates for determining the optimal number of replicate measurements. Conclusions: Although elimination of all sources of variation that can affect laboratory test results is unlikely, the application of analysis of variance (ANOVA) statistical techniques can lead to a cost-effective allocation of resources for estimating the precision of a laboratory test.

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (≤35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both low density (LDL) and high density lipoproteins (HDL). We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDL-C) levels have different HDL subpopulation profiles. In low HDL-C subjects (≤35 mg/dL), the apoA-I-only subpopulation α1 is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and α1 concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only α1 subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C. —Asztalos, B., M. Lefevre, L. Wong, T. A. Foster, R. Tulley, M. Windhauser, W. Zhang, and P. S. Roheim. Differential response to low-fat diet between low and normal HDL-cholesterol subjects. J. Lipid Res. 2000. 41: 321–328.

Cell culture is a valuable method of evaluating the biocompatibility of new dental materials. The purpose of this study was to compare the in vitro biocompatibility of an experimental fluoride composite resin with fluoride and non-fluoride-releasing materials currently available. The dental materials tested were: MQ Silicate (silicate cement), KETAC-CEM and FUJI (type II glass ionomer cements), VISIO DISPERS (a light-cured, nonfluoridated, microfilled composite resin), and FR-17 (an experimental fluoride-releasing composite resin). The Smulow-Glickman (S-G) human, gingival epithelial cell line, which exhibits semidifferentiated characteristics, was used in the study as a test system. Biocompatibility was quantified by counting the viable cells per unit area remaining after 24 and 48 h at two radial distances from cured specimens immersed in the cell culture medium. The test materials were observed to be most toxic to cells nearest the materials. A Time-Distance Cytotoxicity Index (TDCI) was calculated to relate the percentage of dead cells to viable cells at each diffusion distance for each exposure time compared to a nontoxic control. The relative toxicity ranking of the materials tested based on the TDCI was VISIO DISPERS (91%), FUJI (82%), FR-17 (30%), MQ Silicate (23%), and KETAC-CEM (10%), which exhibited the least toxicity. The cytotoxicity of the experimental resin FR-17 was within the range of cytotoxicity of currently accepted restorative materials.

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.

A sample of 310 white, ambulatory elderly adults (n = 116 men, n = 194 women, ages 65 to 99 years) from the Dunedin Program in Florida were examined for serum total and lipoprotein cholesterols, weight, and blood pressure. Women had higher age-adjusted mean levels of total cholesterol (p less than .0001), low density lipoprotein cholesterol (p less than .0001), high density lipoprotein cholesterol (p less than .0005), and weight/height (p less than .0001). Systolic blood pressure increased with age in both sexes, but the trend rose more sharply in women (p less than .0001). Both systolic (p less than .05) and diastolic (p less than .025) blood pressure increased with obesity in women but were unrelated to obesity in men. Approximately 70% (218) of the sample had elevated levels of at least one risk factor. This included 12% (38) having elevated levels of two risk factors and 1% (3) with three. The distribution of risk factors for coronary heart disease in this sample indicates a homogeneous population derived through selective survival remains by age 70 years. These results emphasize the need for additional investigations of genetic and environmental variables promoting longevity.

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

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.

A cross-sectional study of 4074 children, ages 5--17 years, in Bogalusa, Louisiana indicated significant changes of serum lipids and lipoproteins occurring during puberty. These changes could be related to both age and maturation and likely reflect the influence of sex hormones on serum lipoprotein metabolism. Considerable differences were observed in the race/sex groups, with boys showing a more marked decrease of serum total cholesterol, reflecting decreases of beta- and alpha- lipoproteins. While the ratio of mean beta-lipoprotein cholesterol/mean alpha-lipoprotein cholesterol for the white girls and black children remained relatively constant over the age span, the ratio beginning around age 11 years rose dramatically in white boys, reflecting an inordinate decrease of alpha-lipoprotein and an earlier beginning rise of beta-lipoprotein. The observations have important implications for earlier coronary artery disease in white men.

A method is proposed to model individual patterns of growth over time by linear combinations of optimally chosen weighted orthogonal vectors. The goal is to distinguish individuals who track from nontrackers. Nontrackers are defined as those who follow different, usually more complex, growth patterns than trackers. Thus, nontrackers require more vectors than do trackers in modeling their longitudinal observations. A method of specifying the class-specific vectors and individual weights is demonstrated. When the proportion of nontrackers in the population is small, a modified form of the Akaike maximum entropy criterion is used to select the number of vectors appopriate for each person and also to classify each person into a tracking category. When the proportion of nontrackers is large, the modified Akaike criterion together with scatterplots of the growth curve weights are needed to distinguish trackers from nontrackers. The apprach is illustrated with longitudinal observations of height measured in an e...

In a study of 324 term pregnancies, fetal measurements (biparietal diameter, femur length, and abdominal diameter) obtained within one week of delivery correlated more strongly with relative birth weight than with menstrual age.

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.

plasma and aortic tissue lipid changes in atherosclerotic Macaca fascicularis monkeys were studied following various regression regimens for 18 months. Atherosclerosis was induced in groups of 18 Macaca fascicularis monkeys by feeding a semipurified diet containing 43% of the calories as fat and 1.2 mg/kcal cholesterol for 6 months. Five groups of animals were continued on the same diet containing 0.34 mg/kcal cholesterol during the regression period, and were given the following hypocholesterolemic regimens: none (positive controls); D-thyroxine; pyrimidine derivative; cholestyramine; and alfalfa. Another group of animals was maintained on regular monkey chow alone during the regression period (negative control). Among the hypocholesterolemic agents, cholestyramine very effectively reduced the plasma cholesterol, and aorta free- and esterified cholesterol and phospholipids. D-Thyroxine significantly lowered the plasma cholesterol levels but, surprisingly, tissue lipid levels were the highest among the groups studied. Alfalfa, although not as effective as cholestyramine, tended to reduce the plasma and tissue lipids more than other drugs. Pyrimidine derivative actually increased the mean levels of plasma and tissue cholesterol. Plasma cholesterol correlated positively with aortic tissue cholesterol, free and esterified cholesterol. Both the plasma percentage distribution of alpha-lipoprotein and the phospholipid/cholesterol ratio were inversely related to all tissues lipids. Plasma cholesterol accounted for 43% and 30% respectively of the variability in tissue total and esterified cholesterol. Thus the effectiveness of any hypocholesterolemic regimen is probably dependent on achieving a favorable lipoprotein distribution in plasma without any adverse effect on the arterial wall metabolism.

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 R 1 + SV 1 + RV 4 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.

Four cross-sectional epidemiologic studies of children 5–17 years of age were conducted between 1973 and 1982 in the community of Bogalusa, La. Anthropometric, blood pressure and serum lipid variables were measured. Measurement error (precision) and reliability (reproducibility) were estimated for these risk factor variables of coronary artery disease. Precision was less than 0.8 cm for height, 0.8 kg for weight, and 1 mm for triceps and subscapular skinfold over the four surveys. Measurement error for the mercury sphygmomanometer and automatic blood pressure instruments was between 4 and 5 mmHg during this same period. Except for triglycerides and total and α-lipoprotein cholesterols that stabilized at lower levels after the first survey, precision of laboratory variables remained nearly constant over the 9 years of survey. Anthropometric measurements were found to be the most reliable followed next by the laboratory and then blood pressure measurements. These estimates offer guidelines applicable to data collection and processing in future investigations of risk factor variables for coronary artery disease.

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.

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.

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.

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.