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The value of BP measurements and family history of cardiovascular disease in predicting future BP status was studied in 1,501 children, initially 2 to 14 years of age, who were examined four times during an 8-year period in the Bogalusa Heart Study. Correlation coefficients between year 1 and year 9 BPs were as follows for systolic and diastolic BPs, respectively: 0.41 and 0.35 (P less than .0001). These correlations were significant in all age groups. For children in the upper quartile of BP at any one prior examination, the percentage remaining in the year 9 upper quartile ranged from 41% to 52% for systolic BP and 35% to 44% for diastolic BP. Three serial BP measurements in the upper quartile increased the percentages remaining in the upper quartile to 68% for systolic BP and 62% for diastolic BP. Conversely, of those children not in the upper quartile of systolic BP at year 9, 96.8% did not have all three prior measurements in the upper quartile. Family history of hypertension was shown to independently predict year 9 systolic BP status. These results confirm the importance of serial BP measurements and family history of hypertension for the practicing physician.

The composition of proteoglycans was studied in lungs from rabbits treated intratracheally with pronase, CdCl2, or saline. Proteoglycans were extracted from the lungs by 0.5 M and 4.0 M guanidine hydrochloride (GdnHCl) in sequence. Proteoglycans were isolated from the extracts by CsCl isopycnic centrifugation and fractionated by gel filtration on a Sepharose CL-4B column. The lungs from pronase-treated rabbits had approximately 33% greater total uronate than did lungs from saline-treated control animals, whereas CdCl2-treated rabbit lungs had 28% less uronate than did control lungs. Pronase-treated animal lungs had a greater proportion of hyaluronic acid and dermatan sulfate than did the control animal lungs. Relatively greater amounts of uronate were extracted by 0.5 M GdnHCl from the enzyme-treated rabbit lungs than from the CdCl2- or saline-treated animal lungs. The concentrations of hyaluronic acid and heparan sulfate in 0.5 M GdnHCl extract and dermatan sulfate in 4.0 M GdnHCl extract were greater in pronase-treated animal lungs than in control lungs. Gel filtration of proteoglycans sedimented at q greater than 1.45 revealed that pronase-treated animal lungs had proteoglycans smaller in molecular size than those in control lungs. The observations indicate that intratracheal treatment with pronase and CdCl2 alters the composition of proteoglycans in the lung, and such alterations are likely important in the pathogenesis of emphysema.

The Heart Smart Family Health Promotion identified elementary-school-age children with elevated blood pressure (BP), based on sex-, race-, height-specific 90th percentiles, and ponderal index (wt/ht3), based on sex-, race-, and age-specific 90th percentiles (norms developed in the Bogalusa Heart Study). These children and their parents were recruited into a behavioral program aimed at reducing cardiovascular (CV) risk factors for both children and parents and preventing "tracking" of children's elevated risk factors into adulthood. Cardiovascular screening consisted of BP, anthropometric evaluation, serum lipids, and 24-hour urinalysis. Self-reported assessments were personal and family medical history, eating, exercise, smoking, and alcohol behaviors. Both child and parent subjects were predominantly black and female. Data were stable over two baseline measurements and indicated CV risk factor abnormalities in one or both of the parents selected: 67% of the black parents and 25% of the white parents were hypertensive; 91% had positive familial CV history; 41% had total cholesterol greater than or equal to 220 mg/dl; 50% had LDL-C levels greater than or equal to 140 mg/dl; 74% were overweight; 44% were smokers; and 91% were completely sedentary. Using percentile grids to identify children with elevated BP also identifies families with hypertension and associated risk factors.

Despite encouraging reductions in mortality rates from coronary heart disease (CHD), it remains a major public health problem and the leading cause of death in the United States. Although various explanations have been proposed for declining death rates, a consensus exists regarding the importance of lifestyle alterations for risk factor reduction. Because cardiovascular (CV) risk-related behavioral patterns are acquired during childhood, numerous school-based CV health promotion programs have been implemented. The effectiveness of CV research studies for children during the last decade are reviewed. Intervention strategies to prevent heart disease include (1) the population or public health approach and (2) the high-risk approach. The "Heart Smart" model intervention project is utilized to describe these two main strategies. Policy, position statements, and initiatives on CV risk factors from major professional societies and associations, in addition to governmental organizations and offices, are also provided. Primary care physicians, particularly pediatricians and family practitioners, as well as cardiologists can play a crucial role in the prevention of CHD and essential hypertension through efforts and practices in their offices, the schools, and the community at large. The changing and expanding role of physicians interested in preventive child health care is emphasized, including involvement in school- and community-based CV health promotion programs. More comprehensive CV model projects such as "Heart Smart," which intervene on the total school environment, are critical to the reduction of CV disease in the United States and abroad.

Diets of four groups of 10-year-old children (no. = 871, 30% black, 70% white) were examined over 10 years with 24-hour dietary recalls to study temporal trends in cholesterol, fat, and fatty acid intakes in a community. Boys had higher intakes per day and per kilogram body weight than girls for all nutrients (p less than .0001), but there were no sex differences in nutrients per 1,000 kcal. The only racial difference detected was a higher myristic acid intake in whites (p less than .02). There was a 16% decline in dietary cholesterol intake between 1978 and 1982. Three shifts in fatty acid intake increased the P:S ratio from 0.29 in 1973 to 0.45 in 1978: (a) a 5% decline in oleic acid, coupled with a 5% rise in linoleic acid; (b) a quadrupling of linolenic acid; and (c) less stearic and more myristic acid, with palmitic acid unchanged. Total fat intake provided 38% of the calories in each survey, but the changes in proportions of fatty acids paralleled trends in food consumption patterns and nutrient sources. Despite the changes, few children met prudent diet recommendations, and serum total cholesterol and very-low-density-lipoprotein cholesterol levels did not change over time.

To investigate caffeine intake patterns in children, dietary intakes were examined for a biracial sample of 1,284 infants and children. Twenty-four-hour dietary recalls were completed by parents of children aged 6 months and repeated at ages 1, 2, 3, and 4 years; children 10 years old served as their own respondents and were surveyed at ages 13, 15, and 17 years. The sample was 60% white and 40% black. Additional cohorts of 10-year-olds (no. = 686) were studied for temporal trend. Whites consumed significantly more caffeine than blacks as early as 1 year and persisted at a higher intake level from 2 to 17 years. This trend continued whether intake was measured in total milligrams, milligrams per 1,000 kcal, or milligrams per kilogram body weight. Significant sex differences in caffeine intakes per 1,000 kcal occurred among 15- and 17-year-olds (girls greater than boys). Peak periods of consumption occurred at ages 2, 3, 13, and 17. Snacks contributed large quantities of caffeine, particularly for 10-year-olds. Most frequent sources of caffeine were regular carbonated beverages, chocolate-containing foods, and tea. Mean intakes of caffeine for 10-year-olds were consistent from 1973 to 1982. Those observations document caffeine intakes beginning early in life.

In vitro incorporation of 3H-mannose into dolichol phosphate mannose, dolichol pyrophosphate oligosaccharides, and secretory and membrane glycoproteins was investigated in liver slices from streptozotocin diabetic rats. In addition, 14C-leucine incorporation into glycoproteins was studied. 3H-mannose incorporation was significantly less in secretory glycoproteins from diabetic rat liver slices than from control tissues, but 14C-leucine incorporation in these proteins was similar in both groups. Dolichol-phosphate mannose and dolichol-phosphate oligosaccharide synthesis were significantly down-regulated in diabetes. When incubated with insulin, mannosylation of secretory proteins, dolichol-phosphate mannose and dolichol-phosphate oligosaccharides reached control levels in three hours. Dolichol-phosphate mannosyltransferase activity was significantly less in diabetes, while in the presence of insulin, the enzyme activity reached control levels in three hours. These results indicate that key intermediates in glycoprotein biosynthesis are regulated by insulin.

Lipoprotein-glycosaminoglycan (GAG) complexes were isolated from fibrous plaque lesions of human aortas and examined by electron microscopy. After fractionation by gel chromatography and ultracentrifugation, both very low density lopoprotein-GAG and low density lopoprotein-GAG complexes showed particles which were mainly 1,000 to 2,000 A in diameter. Occasional large aggregations 3,000 to 10,000 A in diameter were seen after gel filtration and in the very low density lipoprotein fraction of complexes. In general, the complexes were larger than serum very low density lipoprotein and low density lipoprotein, although serum very low density lipoprotein particles ranged from 250 to 2,000 A. In vitro low density lipoprotein-heparin complexes consisted of spherical particles generally 1,000 to 2,000 A in diameter formed by the aggregation and coalescing of smaller low density liproprotein particles in the presence of heparin and Ca2+. These observations support a concept that GAG of the aortic intimal "ground substance" sequester certain serum lipoproteins in a manner similar to in vitro complexing of lipoproteins and GAG in the presence of Ca2+.

The role of connective tissue of the arterial wall is often overlooked in the consideration of the development of atherosclerosis. In part, this may be due to overemphasis in one area, cholesterol and lipid deposition, yet it is not clear whether the role of lipids is primary or secondary. Virchow, as early as 1856, suggested that atherosclerosis was caused primarily by nonspecific injury and that lipid deposition was a secondary phenomena. It is interesting that current observations are suggesting a mechanism(s), for these phenomena (Wagner and Clarkson, 1973; Ross and Glomset, 1976).

A self-administered rating scale was developed to assess type A behavior in children. It contains 24 items (7-point scale) thought to reflect the major components of type A behavior. The scale was judged to be reliable and yielded the following factors: eagergy (eagerness-energy), restlessness-aggression, leadership, and alienation. 6 tasks were designed (reading, eating, walking, competition, time estimation, and crossing out number) to validate this new measure. A total of 160 predominantly middle-class public school fifth- and sixth-grade children participated in the following factorial design: 2 (classification-type A and type B) X 2 (condition-control and experimental) X 2 (sex-male and female) X 2 (race-white and black). Type A children performed in a more accelerated or intense manner than did type B children on 5 of the 6 tasks (only females exhibited rapid time estimation) as predicted. Also, children performed in a more accelerated or intense manner if they task instructions emphasized speed or intensity for 3 of the tasks (reading, crossing out number, and walking measures). Sex and race differences are also reported. Partial support is provided for the validity and reliability of this new measure.

Two proteoglycan-hyaluronate complexes were extracted from bovine aorta with 4.0 M guanidinium chloride in the presence of protease inhibitors and purified by cesium chloride density gradient centrifugation under associative conditions. Complex I with higher buoyant density had 22% protein and 18% uronate, whereas Complex II had 11% protein and 23.6% uronate. Glycosaminoglycan (GAG) analysis of the complexes indicated that both complexes contained large amounts of hyaluronic acid, 13.6% and 24.0% of the total GAG in Complexes I and II, respectively. Chondroitin sulfates and dermatan sulfate constituted the remainder of the GAG. Chromatography on Sepharose CL 6B suggested that Complex I had an estimated molecular weight of 800,000 and Complex II, 250,000. The complexes were dissociated into proteoglycan and hyaluronate by cesium chloride density gradient centrifugation under dissociative conditions. The proteoglycans free of hyaluronic obtained from the complexes had similar protein and GAG composition. The molecular weight of the proteoglycan was estimated to be 80,000 and that of the hyaluronate of the complex, 90,000.

Chemical analysis of food actually eaten would be the most accurate method for analyzing the diets of children, but this technique is not feasible for most nutrition staffs. An improved 24-hr. dietary recall can be used by a small, well trained staff to collect more reliable data on a large number of school children. Vigilant monitoring of school lunch operations, incorporation of known recipes in the ETNV, and organizing probing techniques are necessary to insure the reliability of the tool. The low coefficients of variation of duplicate recalls noted in the study indicate that the error of measurement between interviewers is small, if the tool is carefully tested and sophisticated before use in the field and if observers are carefully trained by a written protocol.

Free and protein-bound serum sugars and serum lipids were analyzed in 65 adult diabetic patients, 10 age-matched controls, and 24 male medical students for correlation of carbohydrate changes with the extent of retinal, renal, and cardiovascular disease. In diabetic sera, both protein-bound sugars and free mannose, fucose, and hexosamine were significantly elevated; free galactose and inositol were elevated in some diabetic patients, and essentially undetectable in sera from controls. Serum triglycerides and pre-beta-lipoproteins were also elevated in diabetics, but alpha-lipoproteins decreased. Although no specific relationships were observed with the extent of retinal and renal disease, bivariate analyses by Pearson coefficients of correlation showed correlations between levels of serum-free mannose and systolic blood pressure, free hexosamine and duration of diabetes, and serum protein-bound fucose and age. Serum triglycerides and pre-beta-lipoprotein levels correlated with insulin therapy. These are preliminary leads of laboratory studies related to carbohydrate macromolecular changes which might aid in a better understanding of the cardiovascular complications associated with diabetes.

There is considerable controversy on what actually constitutes the ‘early lesion’, on whether all lesions begin in the same way and whether all develop into fibro-fatty plaques. This introduction outlines the morphology and histochemistry of lesions regarded as ‘early’ in terms of chronology and the general pathology of atherosclerosis (Movat et al., 1959; Haust, 1971a; Geer and Haust, 1972).

Since a positive association between blood pressure and plasma glucose level in child populations has been observed previously, we studied this relationship in a stratified random sample of children ages 7-15 years drawn from a total geographic population. We stratified this population (N = 3524) by diastolic blood pressure and weighted the extreme strata. The sample of children (N = 272) was free of secondary hypertensives and was tested by a restricted glucose tolerance test. As a parameter of cellular glucose kinetics, a "peripheral insulin resistance" was defined as one-hour glucose (mg/dl) X one-hour insulin (microU/ml). For white boys, this product showed an increase from 2745 in the low blood pressure strata to 6615 in the high blood pressure strata. To assess the relationship between blood pressure measured during the reexamination and fasting plasma glucose level, we classified the children according to their peripheral insulin resistance in a low, medium, and high group. After controlling for body weight, only white children in the high blood pressure strata with high insulin resistance had a positive association between fasting plasma glucose and systolic blood pressure. The relationship may be initiated by inappropriate intravascular water retention influencing the blood pressure in children with high peripheral insulin resistance and susceptible to hypertension.

Normal levels and trends of cardiovascular disease risk factors in childhood have been well documented by numerous epidemiologic surveys. Expected levels of blood pressure, lipids and lipoproteins, and body size can be determined by the child's physician using race- and gender-specific grids. These grids allow for the identification and follow-up of children with high-risk profiles. Evidence of increased left ventricular mass and vascular changes in renal arteries in association with childhood blood pressure level along with atherosclerotic fatty streak and fibrous plaque development in the aorta and coronary arteries shows that children with elevated risk factors are at risk for early target organ damage. These data demonstrate the potential importance of early intervention on the natural history of cardiovascular disease. Based on our own data from the Bogalusa population, as well as evidence from other epidemiologic investigations in children, the following recommendations can be made, regardless of the risk factor variable under consideration: Cardiovascular disease risk factor variables should be measured carefully and in a serial manner to classify a child as abnormal. Serial measurements serve to reduce the effect of regression to the mean and increase the predictive value of the measurements. The misclassification of normal children into the high-risk category can be avoided by serial and replicate observations. Interventions that have attendant side effects (for example, pharmacologic therapy for high blood pressure) have to be measured against the effectiveness of diet, exercise, and other aspects of primary prevention. Risk factor levels consistently greater than the ninetieth percentile deserve medical attention. Care should be taken prior to using specific grids of normal levels of cardiovascular disease risk factors in children. The measurement techniques employed on individuals should be similar to those used by the epidemiologic study to generate the grids in a reference population. The grids should become part of the child's permanent medical record, as they provide a rapid visual assessment of the cardiovascular disease risk profile over time. High-risk trackers may require more intensive follow-up and will allow for early intervention and an assessment of the efficacy of the intervention program. In conclusion, cardiovascular disease risk factor screening in childhood is quick, effective, and inexpensive. The potential payoff in prevention of adult cardiovascular disease is enormous and allows the physician to provide more comprehensive care to a pediatric population.

This paper provides the rationale, design, description, and evaluation of a unique comprehensive health promotion model, wherein an interdisciplinary group of professionals from three organizations--a medical school, university, and community collaborated to implement a cardiovascular (CV) health project entitled "Heart Smart" on a total school environment (K-6). Preliminary program findings are reported. Major lessons learned are also discussed which suggest a number of recommendations for the successful adoption of a school-based CV health intervention. The expertise and interaction of a multidisciplinary group of health care, research, and educational professionals has been a successful endeavor which has greatly enhanced the quality of the health promotion model for "Heart Smart." More comprehensive models such as "Heart Smart," which intervene on a total school environment, are vital to the reduction of CV disease in the United States and abroad.

We compared serum lipoprotein cholesterol concentrations in a randomly selected subsample (n = 406) population of children (ages 5 to 17 years), as measured by the heparin-Ca2+ and the heparin-Mn2+ precipitation methods. Statistical analysis showed significant differences between results by these methods, especially in values for VLDL- and HDL-cholesterol (mean difference: VLDL-cholesterol, -61 mg/L; HDL-cholesterol, + 108 mg/L). Lipoprotein electrophoretic data indicated that estimating VLDL-cholesterol from serum triglyceride concentrations invariably resulted in higher values for children with an extremely faint pre-beta-lipoprotein band. Among the HDL-subfractions, 14 to 20% of HDL2 was precipitated by heparin-Mn2+ despite the presence of 80 g of albumin per liter. Heparin affinity chromatography of HDL2 in the presence of Ca2+ and Mn2+ showed an interaction of apolipoprotein E-containing HDL2 subfraction only in conditions involving Mn2+. The heparin-Ca2+ procedure precipitated the equivalent of 2 g of beta- plus pre-beta-lipoprotein cholesterol per liter from serum, with no detectable apolipoprotein B in the supernate. We conclude that these precipitations are affected by cation specificity and by differences in lipoprotein makeup of a given individual or population group.

A survey of children for cardiovascular risk factor variables has determined serum lipids and lipoproteins on some 5,000 children from birth through adolescence. Dietary studies have been conducted on a selected sample. Considerable variability of the serum lipids and lipoproteins occurs with significant relationships to age, race, and sex. Serum lipoproteins are altered with obesity especially in white children and a correlation of dietary intake of fat by infants and children had been noted with serum lipids and lipoproteins. A consistent ranking over time or tracking of the serum lipids and lipoproteins, especially beta-lipoprotein, occurs, and a clustering of multirisk factors including high levels of serum total cholesterol and beta-lipoproteins can be observed, especially in the older children. The trend toward increasing interrelationship of multirisk factors suggests an increasing environmental impact with age. The relationships of dietary components with risk factor variables are of a low order, even though children are consuming a relatively high fat, high cholesterol, high salt diet. Dietary factors are potentially the major environmental influence on the high incidence of coronary artery disease. The evidence of the relationship of diet to the serum lipid levels in children warrants further investigation in an effort to understand the precise role of diet in the prevention of adult cardiovascular disease.

Dietary patterns and racial differences in nutrient intake were observed in children 6 months to 4 years of age in the Bogalusa Heart Study. Even in this sample of young children, the composition of the intakes of the majority of children was not compatible with prudent recommendations of less than 35% and 10% of energy from total and saturated fat, respectively. Mean cholesterol intake of the 4-year-old children (390 mg) was approximately one half of the average daily adult levels. The polyunsaturated to saturated fatty acid ratio ranged from 0.41 to 0.53 and sucrose to starch ratio from 1.32 to 1.57, reflecting a high saturated fat and sucrose intake. White children had greater intakes of sucrose than black children; however, total fat and cholesterol intakes were greater in black children. Gender differences were noted among the 2, 3, and 4-year-old children: energy, sugar, and starch intakes were greater in boys, and cholesterol intake per 1,000 kcal was greater in girls. Mean intakes per 1,000 kcal in Bogalusa were higher for fat and carbohydrate and lower for protein than reported in the Second Health and Nutrition Examination Survey. However, when the National Research Council recommended dietary allowances for protein and energy are used for comparison, a more than adequate intake was noted in these children. The data found in this newborn-infant cohort contribute information regarding the early development of dietary habits that likely influence eating behavior in later childhood and adolescence.

Serum lipids and lipoprotein cholesterol fractions were examined in a newborn cohort that was followed from birth to 7 years of age. Although white and female infants had higher cord blood levels of high-density lipoprotein cholesterol (HDL-C) than did black and male infants, respectively, these differences did not persist throughout early childhood. Mean levels of all serum lipids and lipoproteins increased greatly in the first 6 months of life, and by 2 years of age, levels approached those seen in adolescents. Infants consuming cow's milk had higher 6-month levels of serum total cholesterol and low-density lipoprotein cholesterol than did formula-fed infants. However, milk source in infancy did not significantly influence total cholesterol or low-density lipoprotein cholesterol levels at age 7 years. Serum lipid and lipoprotein levels at age 7 years were associated with previously measured levels as early as 6 months of age, and infants with unfavorable levels were likely to have similar adverse levels at 7 years of age. In addition, increases in obesity between 6 months and 7 years of age were positively associated with increases in levels of serum triglycerides. These results suggest that certain persons at increased risk for cardiovascular disease can be identified in infancy.

A self-administered workbook for dietary assessment in small groups was compared with 24-hour dietary recall interviews. Forty-seven 10- to 18-year-olds, in groups of 5 to 8, recorded consumptions during the previous 24 hours and responded to individual recall interviews. Photographs and names of foods served as probes. Standardized food models were used to estimate portions. Nutritionists calculated gram amounts of foods and beverages consumed and analyzed diets for nutrient intakes. Significantly higher niacin (17.4 mg vs. 15.8 mg, p less than .05) and slightly higher protein, animal protein, carbohydrate, and cholesterol (N.S.) were estimated by the group workbook method. Correlations for individual dietary components ranged from 0.69 to 0.93. Dinner accounted for most differences, with statistically greater mean intakes of nine dietary components shown by the workbook method. Thirty-four dinner foods (8%) were not listed in common by the two methods. Sixty-six foods (15%) listed by the two methods had differing gram amounts. Improvements should include increased parental verification of the evening meal, additional training with food models, and periodic rest sessions. The workbook method may expand the time frame studied per individual and increase the number of eating periods examined. Replicate examinations per individual provide measurement of intra-individual variation. This method has applications in studies for which large samples or repeated measures are required.

This paper reports on a study of all school-age children from Bogalusa, Louisiana, examined during the 1973-1974 and 1976-1977 school years by personnel of the Specialized Center of Research-Arteriosclerosis. For these children, the authors estimated the proportion of total variability in risk factors for atherosclerosis resulting from the influences of heredity (h2) and of common environment (c2). The authors' method of classifying half siblings underestimated h2 but overestimated c2. The results showed statistically significant values of h2 for height (0.91), weight (0.90), systolic blood pressure (.137), triglycerides (0.88), beta-lipoprotein (1.16), and alpha-lipoprotein (0.63). In addition, c2 was statistically significant for height (0.20), weight (0.32), triceps skinfold (0.19), systolic blood pressure (0.30), beta-lipoprotein (0.21), and alpha-lipoprotein (0.13). Because of the definition of c2, all traits for which it is significant must increase in value for some Bogalusa environments, and decrease for others. Therefore, for such traits, future analyses may identify favorable common environments that intervention studies can use to decrease the risk of atherosclerosis in Bogalusa. The values found for h2 and c2 in Bogalusa were compared and contrasted with values found for other communities.

The aortic connective tissue components, collagen, elastin, and glycosaminoglycans were isolated and quantitated from monkeys with experimentally-induced fatty streaks, from monkeys on a diet allowing regression of these lesions, and from controls. Although no variations were noted for total, soluble, and autoclavable collagen based on concentration, nonautoclavable collagen was significantly less (p less than 0.02) and elastin was reduced (p less than 0.001) in tissues with fatty streaks. There were no significant differences in total glycosaminoglycan content among the groups, but a large increase of hyaluronic acid (50 to 220 per cent) and a decrease of chondroitin sulfate C (40 to 66 per cent) occurred after regression. Dynamic alterations of arterial connective tissue shown to occur with induction as well as with regression of fatty streaks indicate the importance of connective tissue in maintaining integrity of vascular structures.

We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.

Proteoglycans were extracted from bovine lung gas exchange tissue, pleura, and bronchioles with 4.0 M guanidinium chloride at 5 degrees C in the presence of protease inhibitors. Preliminary purification of the proteoglycans was achieved by an initial CsCl isopycnic centrifugation (rho 0 = 1.33) and through precipitation with cetylpyridinium chloride in 0.5 M KCl. Further purification and fractionation of proteoglycans was achieved by a second CsCl isopycnic centrifugation (rho 0 = 1.45) in 4.0 M guanidinium chloride. Based on the ultracentrifuge profiles and electrophoretic behavior, the major fractions were pooled. They were purified further by gel filtration on Sepharose CL-2B and characterized by extensive analyses. A heparan sulfate proteoglycan was the major proteoglycan identified in the gas exchange tissue and in the pleura. The major proteoglycan component from the bronchioles was a chondroitin sulfate proteoglycan. Approximate molecular weight of 2 x 10(6) for the heparan sulfate proteoglycan from the pleura and chondroitin sulfate proteoglycan from the bronchioles and 1 x 10(6) for the heparan sulfate proteoglycan from the gas exchange tissue were estimated from gel filtration analyses. After incubation with hyaluronic acid, the chondroitin sulfate proteoglycans from the bronchioles showed an increase in specific viscosity and a higher molecular weight compound eluting near the void volume in Sepharose CL-2B column chromatography. The proteoglycans exhibited varied anticoagulant activities in Stypven, partial thromboplastin and thrombin clotting times and inhibited thrombin-induced platelet aggregation.

A large pedigree with high prevalence of heart disease is investigated to analyse the association between polymorphic blood markers and quantitative risk factors for cardiovascular disease. The analysis incorporates a familial correlation structure among the individuals in the pedigree and a generalized power transformation to induce approximate residual normality of the risk factors. A total of 380 marker/risk factor combinations are analysed, and at the normal 1% significance level, positive associations are found between the A antigen of the ABO locus and both serum total cholesterol and low-density lipoprotein cholesterol, and negative associations are found between the B antigen of the ABO locus and serum total cholesterol, and between the B allele of acid phosphatase (AP) locus and systolic blood pressure.

The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes.

Electrolyte and mineral intakes assessed by 24-hour dietary recall were examined for race and sex differences in cohorts of infants and school-age children at 6 months and at 1, 2, 3, 4, 10, 13, 15, and 17 years. A fourfold increase in sodium intake occurred from 6 months to 4 years, and potassium intake doubled. Sodium increased from 0.88 gm at 6 months to 3.21 gm at 4 years and 3.67 gm by 17 years; a slight increase for potassium was noted from 4 to 17 years for boys. Calcium intake was relatively constant from 6 months to 17 years. Boys had higher intakes of sodium and sodium per kilogram body weight than did girls. Black children at 2, 3, and 4 years had significantly higher sodium, potassium, calcium, phosphorus, and magnesium expressed as total intake and per kilogram body weight than white children did. At 6 months, 66% of the infants exceeded the National Research Council's recommended range for sodium. At 1 to 10 years, 90% to 100% and at 13 to 17 years, 60% to 65% exceeded the recommended range. In contrast, 58% to 77% of preschool children and only 5% to 20% of school-age children surpassed the recommended potassium range. Fifty percent to 70% of children more than 10 years old achieved the recommended range for potassium. Approximately half of the children 6 months through 4 years of age met the Recommended Dietary Allowance (RDA) for calcium. Sixty percent to 80% of adolescents ingested less than two-thirds the RDA. Girls had lower intakes than did boys.(ABSTRACT TRUNCATED AT 250 WORDS)

We separately evaluated split specimens of serum for lipoprotein cholesterol in 38 five- to 14-year-old children, by the heparin/Ca2+ precipitation method and the ultracentrifugation/dextran sulfate precipitation method. Statistical analysis of the results indicated an excellent agreement (especially in beta- and alpha-lipoprotein cholesterol values) between results by the two methods. The percentage of alpha-lipoprotein cholesterol (mean +/- SD: 38.6 +/- 5.0) in children further confirmed the earlier observations that cholesterol derived from alpha-lipoprotein in children constitutes a relatively greater part of the serum total cholesterol than is true of adults.

Chondroitin sulfate-dermatan sulfate proteoglycans (PG) were isolated from bovine aorta-intima by extraction with 4.0 M guanidinium chloride in the presence of protease inhibitors and purified through cetylpyridinium complexes. The PG were fractionated by CsCl isopyknic centrifugation into three fractions with different chemical composition. The anticoagulant activity of the PG fractions was studied by Stypven time, partial thromboplastin clotting time (PTT), and thrombin time assays. The three PG fractions delayed coagulation in the three assays. The PG fractions did not affect the ADP and collagen-induced platelet aggregation but inhibited the aggregation induced by 0.2 units per ml. of thrombin. The PG fractions released lipoprotein lipase in rabbits when injected, and the enzyme activity released by the major PG fraction was approximately 60 per cent of that of heparin. This PG fraction interacted with serum low density lipoproteins but not with high density lipoproteins. Certain biologic properties are probably due to the presence of dermatan sulfate in the PG fractions. These studies suggest important functional roles for PG in the arterial wall.

We compared the serum lipoprotein cholesterol concentrations in subgroups of children (n = 360), ages 5-17 years, as measured by the heparin-Ca2+ and preparative ultracentrifugation methods. Children were grouped from the total population on the basis of their previous results for serum beta- and pre-beta-lipoprotein cholesterol (Group I: low beta- and low pre-beta-; Group II: high beta- and low pre-beta; Group III: high beta- and high pre-beta-; Group IV: low beta- and high pre-beta-). The values for very-low-density (VLDL) cholesterol by ultracentrifugation method were 44, 53, 15, and 10 mg/L greater than the values for pre-beta-lipoprotein cholesterol by the heparin-Ca2+ method in Groups I, II, III, and IV, respectively; the differences were not significant in Group IV. The values of low-density (LDL) cholesterol were 64, 137, 144, and 73 mg/L less than the values for beta-lipoprotein cholesterol in Groups I, II, III, and IV, respectively (p less than 0.005). On the other hand, high-density (HDL) cholesterol concentrations in the respective four groups were 10, 37, 93, and 52 mg/L greater than alpha-lipoprotein cholesterol concentrations; the differences were significant for Groups II, III, and IV (p less than 0.005). Overall, the values for LDL-cholesterol correlated highly with beta-lipoprotein cholesterol (r = 0.94), whereas correlations for VLDL- and HDL-cholesterol values with pre-beta-lipoprotein cholesterol (r = 0.76) and alpha-lipoprotein cholesterol (r = 0.77) were somewhat lower. The differences between these two methods may result from their different operational definitions for measuring serum lipoproteins and the possibility that without appropriate corrections the values obtained by preparative ultracentrifugation do not serve as reference values.

It is unknown how different calculation procedures for quantitating foods can influence variation in nutrient values. Precision of calculation and transcription, plus a double-checking procedure, is standard Bogalusa Heart Study protocol. These procedures likely would minimize human error. Nevertheless, converting gram weight values for food (BHS) into the closest household measure (NCC) could influence analysis. If calculation procedures are similar, different nutrient values in 2 food composition tables would then account for most variation in results. Consistently lower values for sucrose by the NCC likely reflect the program's carbohydrate rationale, i.e., the classification of total carbohydrate into 3 categories--sucrose, starch, and other. Sucrose may then be underestimated, as the other carbohydrate value "indicates combinations of sugars and/or sugars and starch," such as those found in commercial products. The ETNV total sucrose value is a sum of the naturally occurring sucrose and sucrose added in commercial preparations. For this small sample, the group means of selected nutrients by 2 dietary computer analyses systems are quite similar, with the exception of sucrose. With fairly large standard errors for most components, a large sample might create a statistically significant difference. Periodic comparability checks are essential to document quality and similarity of data bases. Quality control procedures in dietary methodology should be analogous to techniques for physiological and biochemical measures, e.g., the Centers for Disease Control and LRC methods and standards. Low-level correlations observed between dietary intakes and risk factor variables imply no association. Comparison and improvements of data bases are timely and should increase the probability of identifying associations between dietary components and indicators of diseases.

Clinical and anatomical observations from the Bogalusa Heart Study over a 15-year span provide data on cardiovascular risk factors and the early natural history of arteriosclerosis. These studies established that: cardiovascular risk can be predicted in early life; interrelationships of risk factors in children are similar to those observed in adults; and concentrations of serum lipoproteins change during sexual maturation. Strategies involving the general population and high-risk groups should be considered to help reduce atherosclerosis and coronary artery disease. Active modification of risk factors in the general populace would include using such methods as screening, education, and mass-media campaigns. Educational promotion ("Heart Smart") has already been implemented in the New Orleans area, focusing on using the total school environment to teach cardiovascular health and to encourage children to adopt desirable lifestyles. Inclusion of cardiovascular health education into general educational studies of children should be a major objective of the future.

The interactions of a chondroitin sulfate-dermatan sulfate proteoglycan with serum very low (VLDL), low (LDL), and high density (HDL3) lipoproteins were studied with special reference to the nature of the interaction of LDL and the proteoglycan. The proteoglycan formed insoluble complexes with VLDL and LDL, but no complex was formed with HDL3. The proteoglycan (40 micrograms/ml) converted 98% of added LDL (150 micrograms of cholesterol/ml) into insoluble complex at a Ca2+ concentration of 30 mM. Physiologic concentrations of albumin inhibited insoluble complex formation with VLDL and LDL by 61.5 and 40.7%, respectively. The proteoglycan formed soluble complexes with LDL even in the absence of Ca2+. Optimum soluble complex formation occurred when the medium contained 66.6 micrograms of proteoglycan and 166.6 micrograms of LDL cholesterol/ml. Specific modifications of the lysine and/or arginine residues of LDL prevented complex formation with the proteoglycan, thus indicating the requirement of the positive charges of the protein moiety of LDL in the interaction. Removal of the protein core or the glycosaminoglycan chains of the proteoglycan prevented interaction with LDL. Desulfation of the proteoglycan molecule also inhibited complex formation with LDL. Thus, the native state of the arterial proteoglycan molecule confers optimum charge density for specific interaction with serum apoprotein B-containing lipoproteins.

Robust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait-marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL-C levels, the HDL-C to apo A1 ratio, the LDL-C to apo B ratio, and a measure of relative content of cholesterol in HDL-C and LDL-C. Linkage between haptoglobin and the HDL-C/apo A1 ratio was suggested, with a lod score of 1.72 at theta = 0.05.

Caucasian and Afro-American schoolchildren participating in a community-based cardiovascular screening program in Bogalusa, Louisiana are characterized with respect to phenotypic and allelic frequencies at 10 enzymatic and 3 nonenzymatic polymorphic loci. Biracial gene frequencies in Bogalusa are compared with those reported for other populations of similar ethnic composition. Intra- and interracial genetic distances within and between the racial subpopulations of Bogalusa and Seattle, Washington are compared. While the comparisons do not support the concept that northern, urban blacks have more Caucasian admixture than blacks residing in the rural South, they do suggest microdifferentiation of the two white populations.

Since atherosclerosis and essential hypertension are believed to begin asymptomatically in early life, much interest has recently been shown in the study of risk factor variables in children. Extensive information is now available on cardiovascular (CV) disease risk factor variables of children in a general population, somewhat comparable to information from similar studies of adults (Monograph 1978). Additional research is now providing longitudinal observations following time-course changes of CV risk factor variables (Voors et al. 1979b, Frerichs et al. 1979) and determining how levels during the pediatric years may relate to adulthood, when the risk of coronary heart disease or essential hypertension can be judged by morbid events. Although there is a lack of understanding of the clinical significance and aftermath of disease in children, such as it occurs in adults, there are certain advantages to studying children. Heretofore, most of the epidemiologic studies described adult disease during a time when biologic changes of risk factors are less obvious. For example, in adults, stature, body weight, and serum total cholesterol change relatively little when compared to the dramatic changes that occur in the developing infant or child (Berenson et al. in press). These temporal changes in children occur during life periods when clues to mechanisms responsible for different levels of risk factor variables are available. The observation of race and sex contrasts enhances the potential usefulness of a pediatric study.

We evaluated the variability in total cholesterol concentrations in serum in a large population of children over a period of time, to help us discern the limitations in reliability of current clinical laboratory methods for its analysis. We analyzed sera from a population of approximately 4000 children over a four-year period, quality-control sera, pooled sera, and surveillance samples from the Centers for Disease Control over a seven-year period, with a Technicon AutoAnalyzer II. Two methods of correction were suggested to adjust deviations in yearly serum total cholesterol means: yearly screening data were corrected on the basis of monthly variability in pooled-serum determinations and on the basis of deviations from values suggested by the Centers for Disease Control. Both correction methods were insufficient. These changes occur very slowly, and unless there is close monitoring and frequent comparison with a known standard, changes in laboratory results still can occur.