Edward R. Dalferes

Racial differences of parameters associated with blood pressure levels in children—The Bogalusa Heart Study

Racial differences in prevalence of essential hypertension are well known. In order to explore these differences at an early age in terms of etiology, we investigated schoolchildren in an entire, biracial community. A sample of 278 children, stratified by diastolic (fourth-phase) blood pressure and specific for age, race, and sex, was reexamined 1--2 yr after initial observation for the following: (1) a physical examination and urinalysis to exclude secondary hypertension; (2) 24-hr urine sodium, potassium, plasma renin activity, and serum dopamine beta-hydroxylase; (3) 1-hr oral glucose tolerance test; and (4) heart rate and blood pressure at rest and under standarized physical stress. We found that 24-hr urine sodium was positively associated with blood pressure level as measured on the same day for the high blood pressure strata of black children. Urine potassium excretion was lower in blacks than in whites, although their intakes seemed equal. In the high blood pressure strata especially, black boys had lower renin activity than whites, and the resting-supine and stressed systolic blood pressures were higher in black boys than in any other group. In these black boys, resting and stressed systolic pressures were negatively related to plasma renin activity. On the other hand, dopamine beta-hydroxylase levels in white children were higher than in blacks for all blood pressure strata, and in the high blood pressure strata white children had higher 1-hr glucose levels and faster resting heart rates than black children. Different mechanisms may play a role in and contribute to the early stage of essential hypertension.

Plasma Homocysteine Distribution and Its Association With Parental History of Coronary Artery Disease in Black and White Children The Bogalusa Heart Study

BACKGROUND Elevated homocysteine is associated with increased risk for coronary artery disease (CAD) in adults, but its distribution in children is not well documented. We examined the distribution of homocysteine in children and its relation to parental history of CAD. METHODS AND RESULTS A subsample of 1137 children (53% white, 47% black) aged 5 to 17 years in 1992 to 1994 examined in the Bogalusa Heart Study (n=3135), including all with a positive parental history of CAD (n=154), had plasma homocysteine levels measured. Homocysteine correlated positively with age (r=0.16, P=0.001). No race or sex differences in homocysteine levels were observed; geometric mean (GM) levels were 5.8 micromol/L (95% CI, 5.6 to 6.1) among white males, 5.8 micromol/L (95% CI, 5.5 to 6.0) among white females, 5.6 micromol/L (95% CI, 5.4 to 5.8) among black males, and 5.6 micromol/L (95% CI, 5.4 to 5.9) among black females. Children with a positive parental history of CAD had a significantly greater age-adjusted GM homocysteine level (GM, 6.7 micromol/L; 95% CI, 6.4 to 7.1) than those without a positive history (GM, 5.6 micromol/L; 95% CI, 5.4 to 5.7); this relation was observed in each race-sex group. CONCLUSIONS Higher homocysteine levels were observed among children with a positive family history of CAD. Additional studies should elucidate the contribution of genetic, dietary, and other factors to homocysteine levels in children.

Acid mucopolysaccharides of human aorta

Summary Concentrations of acid mucopolysaccharides (MPS) in the aortic intima and outer layers (externa) with varying extent and severity of atherosclerosis have been studied in Negro females. An increase initially, followed by a decrease, of MPS concentrations was observed as the disease extended from 10 to 55 %. The increase of MPS was characteristic of the fatty streaks and the decrease characteristic of fibrous plaques, complicated and calcified lesions. Chondroitin sulfate B concentrations paralleled the extensiveness of the fatty streaks while it was almost absent in intimai tissue from vessels with fibrous plaques. The chondroitin sulfate B increase may represent an intimai reaction, the disappearance of which coincides with advancement of the disease. It appears that the variations in concentration of MPS in the aorta represent diffuse metabolic changes. Certain early changes predispose to the initiation of atherosclerosis, but progression of the disease is associated with a marked alteration of the content of specific MPS.

Carbohydrate macromolecules and atherosclerosis

Abstract This review describes the characteristics of the carbohydrate macromolecules that are found in the matrix of the arterial wall and their possible role in the pathogenesis of atherosclerosis. The chemical and histochemical methods used in studying the acid mucopolysaccharides (MPS) of the aorta are discussed, and information pertaining to changes in the arterial MPS in aging and atherosclerosis and in susceptible and nonsusceptible animal species is presented. The active metabolic state of arterial MPS and their changes during atherosclerosis are outlined. An interaction of MPS and lipoproteins to form MPS-lipoprotein complexes is discussed; these MPS-lipoprotein complexes are important to the development of the fatty lesions of atherosclerosis. In addition, a survey is presented of another group of carbohydrate macromolecules, the glycoproteins of the aorta. Their chemical structure, possible function, and the changes that occur in atherosclerosis are also described.

Acid mucopolysaccharides of human aorta: Part 1. Variations with maturation*

Summary Acid mucopolysaccharide (MPS) contents in the intima and remaining outer wall of human aortas were studied to observe variations with age. Attempts were made to dissociate changes occurring with aging from those related to atherogenesis by the careful selection of vessels. MPS were isolated from 76 female aortas with and without lesions, and compared to 15 samples from Negro females, the only ones available essentially free of atherosclerotic disease. Aortas available in this population limits the study from extending into older age groups. Detailed MPS analyses were carried out on the lesion-free vessels. The total amount of MPS increases to around the third decade, with more marked changes of compounds occurring in the intima. Chondroitin sulfates C and B both increased in concentration in the intima and then decreased; chondroitin sulfate A progressively increased, while hyaluronic acid and heparitin sulfate showed a tendency to reach peak levels at an early age and then only gradually decreased. Other compounds were noted, but were not in sufficient amount to be clearly characterized. The importance of observing changes of each specific MPS compound and a careful selection of tissue to be studied are to be emphasized in these types of observations.

Acid mucopolysaccharides of fatty streaks in young, human male aortas.

Abstract The mucopolysaccharide (MPS) content and composition of fatty streaks (posterior thoracic and abdominal aorta) were compared to carefully selected un-involved aortic intima (anterior thoracic). An altered composition of MPS in the very earliest lesions occurring in adolescent males was observed. An increase of MPS, chondroitin sulfate C in particular, was found in the fatty streaks associated with spindle cell and extracellular lipid in 12 to 25 year age group. The area of the aorta more susceptible to atherosclerosis showed the most striking changes. These studies are a further indication that MPS contribute to the development of fatty streaks, likely through their interaction with lipids.

Lipoprotein-hyaluronate associations in human aorta fibrous plaque lesions

Lipoproteins and glycosaminoglycans were isolated from human aorta fibrous plaque lesions by isotonic saline extraction and treatment with elastase. Hydrolysis by elastase, using suitable inhibitors of nonspecific proteases, yielded about twice the amount of cholesterol and four times more GAG than saline extraction. Bio-Gel A-50m column chromatography of elastase-solubilized materials gave a fraction which contained lipoproteins of 1.006 and 1.063 floating densities and hyaluronic acid. Immunologically the lipoproteins resembled serum apoB-containing lipoproteins. Two species of hyaluronates with estimated molecular weights of 400,000 and 75,000 were observed. In addition to hyaluronate, elastase solubilized other GAG which were not associated with lipoproteins. Association of hyaluronate as the only GAG in the elastase-solubilized lipoprotein fraction emphasizes the important role that hyaluronate may play in the aggregation or entrapment of macromolecules such as lipoproteins in the arterial connective tissue matrix.

Black-white differences in postprandial triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men.

Black-white differences in serum triglycerides and high-density lipoprotein (HDL) cholesterol concentrations are known. However, the metabolic basis for these differences is not clear. This study determined the magnitude of postprandial triglyceride concentrations, lipoprotein lipase and hepatic triglyceride lipase activities in postheparin plasma, and serum lipid and lipoprotein cholesterol concentrations in healthy young adult black men (n = 22) and white men (n = 28). Postprandial triglyceride concentrations were measured at 2, 3, 4, 5, 6, and 8 hours after a standardized test meal. Serum lipid and lipoprotein cholesterol concentrations were similar between the races in this study sample. However, incremental (above basal) increases in triglycerides were significantly greater in white men versus black men at 2 hours (P = .01) and tended to be greater at 3 hours (P = .12) and 4 hours (P = .06) after the fat load. In a multivariate analysis that included age, race, apolipoprotein E (apoE) genotype, fasting triglycerides, obesity measures, alcohol intake, and cigarette use, fasting triglycerides (P = .04) and, to a lesser extent, race (P = .07) were associated independently with the 2-hour incremental increase in triglycerides. The incremental triglyceride response correlated inversely with HDL cholesterol in both whites (r = -.38, P = .04) and blacks (r = -.59, P = .004). Lipoprotein lipase activity was higher (P = .049) and hepatic triglyceride lipase activity lower (P = .0001) in black men compared with white men; racial differences persisted after adjusting for the covariates. While lipoprotein lipase activity tended to associate inversely with the postprandial triglyceride concentration in both races, hepatic triglyceride lipase activity tended to correlate positively in whites and inversely in blacks. These results suggest that compared with whites, blacks may have an efficient lipid-clearing mechanism that could explain the black-white differences in lipoproteins found in the population at large.

Analyses of glycosaminoglycans by gas-liquid chromatography and the nature of hexuronic acids in heparin☆

Abstract Glycosaminoglycans in microgram quantities were analyzed by gas-liquid chromatography (GLC). Analyses were made of the total and individual hexuronic acids and hexosamines. Glycosaminoglycans were hydrolyzed with formic acid (90%) at 100° for 20 hr in nitrogen atmosphere. The resulting uronic acids and/or lactones were trimethylsilylated (TMS), and the TMS derivatives were analyzed by GLC on an Apiezon column at 190°. Glucuronic and iduronic acids each showed two peaks on the chromatograms. The areas of the peaks were found proportional to the concentration of the sugar. Uronic acids in several polysaccharides were determined by this method using α-methyl- d -glucoside as an internal standard, and the results were found in good agreement with theoretical values. The method, however, was not found suitable for quantitative analysis of total uronic acids in heparin and heparan sulfates due to incomplete hydrolysis of these polysaccharides even after 40 hr. The nature of uronic acids in heparin was investigated by making use of GLC. Peaks corresponding to the retention times of iduronic acid and/or lactones were observed in the chromatograms of heparin after hydrolysis with formic acid. Effluent fractions from GLC column corresponding to peaks on the chromatograms of hydrolyzed heparin were collected and the identity of these fractions with xylose, iduronic acid, and glucuronic acid was established through their infrared spectra. Although there are limitations in determining the total amount of hexuronic acids in heparin and heparan sulfate by the methods described, these techniques are very useful in resolution of ratios of the different hexuronic acids and detection of trace quantities not heretofore possible.

Review: Atherosclerosis and its Evolution in Childhood

Cardiovascular risk factors in childhood are related to arterial wall changes that lead to atherosclerotic coronary artery disease in later life. Atherosclerosis begins early in life. The observations of early arterial wall connective tissue changes and accompanying early lipid deposition show the importance of understanding cardiovascular risk factors in children. Since risk factors found in childhood are potentially predictive of adult coronary heart disease, methods for prevention of atherosclerosis should begin in children. Rational strategies should be directed to removing atherogenic forces that work in a child at high risk. Primary prevention of atherosclerosis has its maximal potential when begun before advanced irreversible lesions can occur. Consideration needs to be directed to how cardiovascular connective tissue changes and lipid and calcium deposition can be modulated in the injury and healing processes. It is important to recognize that adult coronary artery disease is really a major pediatric problem.