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Biomedical subjects

D S Freedman

Publications and source records attributed to D S Freedman.

At least 73 records · Page 4Linked to original sources

Cardiovascular risk in parents of children with extreme lipoprotein cholesterol levels: the Bogalusa Heart Study.

Fasting serum lipids, lipoprotein cholesterol, and other cardiovascular disease risk factors were examined in 321 natural parents of children with low and/or high levels of beta- and pre-beta-lipoprotein cholesterol. Parents of children from low pre-beta-lipoprotein groups had elevated alpha- and lower pre-beta-lipoprotein cholesterol levels. Parents whose children had high beta-lipoprotein cholesterol levels also had high serum total and beta-lipoprotein cholesterol levels. Parents of children with high levels of both beta- and pre-beta-lipoprotein cholesterol had a high prevalence of both abnormal risk factor levels, as well as clinical evidence of early coronary artery disease (before age 50 years). These observations show that parents of children with high beta- and/or pre-beta-lipoprotein cholesterol levels have greatly enhanced risk for cardiovascular disease, and children mirror their parents' lipoprotein cholesterol levels. These observations emphasize the need for cardiovascular risk evaluation early in life, especially in high-risk families.

Adolescent↗

Black-white differences in aortic fatty streaks in adolescence and early adulthood: the Bogalusa Heart Study.

Although white adults have more extensive aortic surface involvement with fibrous plaques than do blacks, adolescent blacks have more aortic fatty streaks (FS) than do whites of similar ages. Possible determinants of these racial differences in aortic surface involvement with FS were therefore examined in 44 decedents who had previously been examined as part of the Bogalusa Heart Study. Ages at death ranged from 6 to 27 years (mean, 18 years); the median interval between the last risk factor examination and death was 3.5 years. More extensive aortic surface involvement with FS was observed in blacks (n = 11) as compared with whites (n = 33; 37% vs 16%, p = .0003). This racial difference was independent of age at death, and was seen in both male and female subjects. Black-white differences in several of the previously measured risk factors (serum lipids and lipoproteins, blood pressure, and obesity) were also observed, and in both races, aortic FS were related to several of these characteristics. (For example, the correlation between levels of low-density lipoprotein cholesterol and aortic FS was 0.49 in whites and 0.73 in blacks.) However, even after controlling for antemortem levels of risk factors, blacks had an additional 16% surface involvement with aortic FS as compared with whites (p less than .001). These findings suggest that the more extensive surface involvement of the aorta with FS in young blacks is not due to differences in clinical risk factors. Because more extensive raised lesions are found in white adults, the transition of FS to advanced atherosclerotic lesions may differ in whites and blacks.

Adolescent↗

Secular trends of obesity in early life: the Bogalusa Heart Study.

Secular changes in height and weight measurements were examined in five- to 14-year-olds from 1973 to 1984. The age-sex specific 85th percentile was used to classify persons as overweight (based on ponderal index; kg/m3). Secular increases in weight (2.5 kg), and ponderosity (0.5-0.7 kg/m3) were found. Gains in ponderosity over the 11-year period were greater at the 75th percentile than at the 25th percentile, and the prevalence of overweight increased from 15 per cent to 24 per cent.

Age Factors↗

The association between cardiovascular response tasks and future blood pressure levels in children: Bogalusa Heart Study.

Children were selected from a total community survey and categorized into three blood pressure (BP) groups (low less than 10 percentile, midrange 10 to 90 percentile, high greater than 90 percentile) based on resting diastolic pressure (DBP). To examine the relationship of cardiovascular reactivity with BP levels 4 years later, three cardiovascular response tasks (orthostatic, handgrip, and cold pressor) were administered. Partial correlations, adjusted for initial resting BP, showed that peak BP responses to the three tasks were related to future resting systolic and diastolic BP. Further analyses showed that DBP reactivity was related to future BP tracking in children with high DBP levels. In the high DBP group, while resting DBP levels did not differ for trackers vs nontrackers, peak DBP responses to each of the three tasks did (orthostatic, p less than 0.001; handgrip, p less than 0.05; cold pressor, p less than 0.01). The combination of resting and peak BP levels may provide more powerful predictions of future BP levels in children.

Adolescent↗

Black-white differences in serum lipoproteins during sexual maturation: the Bogalusa Heart Study.

Serum lipid, lipoprotein cholesterol, and apolipoprotein (A-I and B) levels were compared between 940 black and 1710 white children who were between the ages of 5 and 17 years. Stratification, matching, and analysis of covariance were used to determine whether black-white differences in levels of serum triglycerides (TG), very low- (VLDL-C), and high- (HDL-C) density lipoprotein cholesterol, and apolipoprotein A-I (apoA-I) could be explained by differences in sexual maturation, obesity, cigarette smoking, alcohol intake, oral contraceptive use, insulin, and glucose. Independently of these covariates, blacks had elevated levels of HDL-C and apoA-I (males only), and whites had increased levels of TG and VLDL-C. All differences were statistically significant at the 0.001 level. In addition, racial contrasts tended to be greater in sexually mature, as compared with prepubertal, males; a similar divergence of levels with sexual maturation was not observed in females. HDL-C levels in white males were partially explained (R2 = 0.12) by sexual maturation, insulin, and obesity; apoA-I levels were associated with only sexual maturation and insulin. Racial differences in levels of serum lipids, lipoprotein cholesterol, and apoA-I in early life, therefore, exist independently of differences in several lipoprotein determinants. Since the initial stages of atherosclerosis begin in the young, these black-white lipoprotein contrasts may influence differences in adult coronary heart disease rates between the races.

Adolescent↗

Relation of body fat distribution to hyperinsulinemia in children and adolescents: the Bogalusa Heart Study.

The relation of body fat distribution to plasma levels of glucose and insulin during an oral glucose tolerance test was examined in 355 Black and White school-age children. Both central and peripheral fat were similarly related to fasting, 30-min, and 1-h glucose. Unlike peripheral fat, central body fat was more strongly related to the 1-h insulin response (r = 0.35 vs 0.26); this association remained significant for central fat independent of peripheral fat (r = 0.18). The strong relation of central fat to insulin response was noted in both races and sexes but not in either sexually immature or relatively thin children. These findings indicate that, even in early life, a central body fat pattern relates positively to insulin response to glucose load. Thus, knowledge of body fat localization may help identify persons most susceptible to hyperinsulinemia in early life.

Adipose Tissue↗

Adverse influences of alcohol, tobacco, and oral contraceptive use on cardiovascular risk factors during transition to adulthood.

Risk factors for cardiovascular disease were measured in 990 young adults, aged 17-24 years, in a 1982-1983 survey of the biracial (black-white) community of Bogalusa, Louisiana. Even after controlling for age and obesity, several lifestyle factors (cigarette smoking, alcohol consumption, and oral contraceptive use) were independently related (p less than 0.05) to levels of serum lipids, lipoprotein cholesterol fractions, and blood pressure. Oral contraceptive use was associated with increased levels of both serum triglycerides (20 mg/dl, blacks; 25 mg/dl, whites) and low density lipoprotein (LDL) cholesterol (19 mg/dl, whites), and decreased levels of high density lipoprotein (HDL) cholesterol (-6 mg/dl, whites). Linear regression analyses also showed that cigarette smoking was associated with elevated levels of serum triglycerides (ranging from 15 to 26 mg/dl) and decreased levels of HDL cholesterol (ranging from -9 to -11 mg/dl) in white males and females. Although persons who smoked cigarettes were also likely to consume alcohol, alcohol intake in nonsmokers was positively associated with levels of serum triglycerides, LDL cholesterol, and very low density lipoprotein cholesterol in white males, and with blood pressure levels in black males. A statistically significant association between alcohol intake and HDL cholesterol levels (r = 0.24) was observed only in white females who did not smoke. These adverse influences of lifestyle factors on cardiovascular disease risk may provide a rational basis for intervention during adolescence and early adulthood.

Adolescent↗

Designation of children with high blood pressure--considerations on percentile cut points and subsequent high blood pressure: the Bogalusa Heart Study.

The effects of changing the percentile cut points of prior blood pressure measurements (both single and serial examinations) on prediction of subsequent high blood pressure, and of the definition of subsequent high blood pressure were assessed in 1,501 children from Bogalusa, Louisiana. Subjects were 2-14 years old at initial examination (year 1, 1973-1974) and were reexamined three, five, and eight years after the initial examination. Increasing the stringency of the prior measurement cut point resulted in increased specificity and positive predictive value, but decreased sensitivity and negative predictive value. For prediction of subsequent systolic blood pressure at the 90th percentile from year 1 levels, increasing the year 1 cut point from the 80th to the 95th percentile resulted in decreased sensitivity from 42.8 to 13.0%, and increased specificity from 83.0 to 97.3%. For systolic pressure, requiring all prior serial measurements to be above specified cut points resulted in further increases in specificity (maximizing at 100%) and decreases in sensitivity (minimizing at 2.1%). Using a year 1 cut point at the 90th percentile, increases in the definition of subsequent high blood pressure (from the 80th percentile to 140/90 mmHg or on treatment, respectively) resulted in increased sensitivity (from 20.5 to 33.3%) and negative predictive value, with decreasing specificity (from 93.9 to 91.3%) and positive predictive value. The results indicate that use of stringent criteria (serially at the 95th percentile) to identify children at risk for future essential hypertension will result in a substantial portion of the childhood population who will escape early identification but who will develop adult hypertension. Less stringent criteria will increase sensitivity and thereby provide the opportunity for primary prevention to a larger portion of the general childhood population who are at high risk for adult hypertension.

Adolescent↗

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.

Adolescent↗

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

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

Adolescent↗

Body fat patterning and blood pressure in children and young adults. The Bogalusa Heart Study.

The relationship of central body fat (measured by subscapular skinfold) and peripheral body fat (measured by triceps skinfold) to blood pressure was investigated in 3784 subjects aged 5 to 24 years old from the biracial community of Bogalusa, Louisiana. After adjustment for height, age, sex, and race, significant relationships were found for both central body fat (r = 0.19 and 0.14, p less than 0.0001) and peripheral body fat (r = 0.15 and 0.12; p less than 0.0001) with systolic and diastolic (fourth phase) blood pressure, respectively. However, the relationship between peripheral body fat and blood pressure, after controlling for the level of central body fat, was negligible (r = 0.00 and 0.01 for systolic and diastolic blood pressure, respectively). In contrast, the central body fat-blood pressure relationship remained statistically significant even after controlling for the peripheral body fat level. For central body fat, the partial correlations with systolic blood pressure were highest in young children (r = 0.15), dropped slightly during adolescence (r = 0.12), and became nonsignificant only in 18- to 24-year-old female subjects; correlations remained high in both black and white 18- to 24-year-old male subjects (r = 0.18 and 0.16, respectively). Mean levels of systolic blood pressure from the lowest to the highest quartile of central body fat ranged from 100.4 to 108.9 mm Hg. The adult hypertension-central body fat relationship, which has been shown by others, appears to exist in children. Continued efforts at early identification and prevention of obesity in children are warranted.

Adipose Tissue↗

Persistence of juvenile-onset obesity over eight years: the Bogalusa Heart Study.

The persistence of obesity and overweight over eight years was assessed in a biracial (Black-White) cohort of 1,490 two-to 14-year-olds. Initial levels of triceps skinfold thickness (TRSF) and Rohrer index (weight/height3) were moderately predictive of subsequent levels: r = 0.54 and 0.67, respectively. However, TRSF and Rohrer index tended to track most strongly in Black females (r = 0.64 and 0.72) and less well in both White females (r = 0.45 and 0.57) and preschool children (r = 0.45 and 0.54). Based on elevated levels of TRSF or Rohrer index, children were classified as obese or overweight, respectively. Of the 222 children who were initially above the 85th percentile for TRSF, 43 per cent remained obese after eight years. Persistence of overweight was slightly greater at follow-up, with 50 per cent of initially overweight children staying above the 85th percentile for Rohrer index. Severe, initial obesity/overweight (greater than 95th percentile) and consecutively elevated levels increased the probability of remaining obese/overweight. Results indicate that moderate, juvenile-onset obesity is malleable, but that the child who is extremely obese over consecutive examinations is likely to become an obese adult.

Adolescent↗

Cardiovascular risk factors from birth to 7 years of age: the Bogalusa Heart Study. Serum lipids and lipoproteins.

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.

Age Factors↗

Cardiovascular risk factors from birth to 7 years of age: the Bogalusa Heart Study. Design and participation.

Cardiovascular risk factor variables were examined in a cohort of 440 infants from birth through 7 years of age. Anthropometric measures, BP, serum lipid and lipoprotein values, and dietary intake data were obtained according to detailed protocols. Various quality controls to ensure the collection of valid and reliable data were instituted. Participation remained high throughout the study with 80% of the children examined at 6 months and 60% at 7 years of age. Rates were slightly higher for black than for white children. Children born in the private hospital were more likely to continue in the study than children born in the charity hospital. Children of parents examined when the child was 2 years of age were more likely to be examined during the preschool phases, but parental examination was not related to child examination when the child was 7 years of age. As in studies of school-aged children, measurement errors were lowest for height, weight, and serum total cholesterol. Measurement errors for BP were highest at the younger ages, particularly for diastolic BP. Examination of a newborn cohort throughout time affords the opportunity to study early development of relationships and tracking of cardiovascular risk factors.

Absenteeism↗

The relation of apolipoproteins A-I and B in children to parental myocardial infarction.

Clinical studies suggest that serum levels of apolipoproteins A-I and B may be more strongly related to coronary artery disease than are their respective lipoprotein-cholesterol fractions. Therefore, we assessed the association between levels of apolipoprotein B, apolipoprotein A-I, lipids, and lipoprotein cholesterols in children and the reported histories of myocardial infarction in their parents in a survey of 2416 black and white school-age children. As compared with children whose fathers did not report a myocardial infarction, those whose fathers reported having had an infarction (n = 139) had a lower mean level of apolipoprotein A-I (137 vs. 141 mg per deciliter; P = 0.04) and a lower ratio of low-density lipoprotein cholesterol to apolipoprotein B (1.08 vs. 1.11; P = 0.007), along with a higher ratio of apolipoprotein B to apolipoprotein A-I (0.64 vs. 0.61; P = 0.04). These associations existed independently of the children's race, sex, age, and history of obesity, smoking, alcohol intake, and use of oral contraceptives. Children whose mothers reported having had a myocardial infarction (n = 56) had no decrease in the ratio of low-density lipoprotein cholesterol to apolipoprotein B, but they tended to have an elevated ratio of apolipoprotein B to apolipoprotein A-I. In contrast, serum lipoprotein-cholesterol fractions in children were not related to myocardial infarctions in either parent. These results provide further evidence that apolipoproteins are more strongly related to the risk of cardiovascular disease than are lipoprotein-cholesterol fractions.

Adolescent↗

Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study.

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.

Adolescent↗

Fasting plasma glucose and insulin levels and their relationship to cardiovascular risk factors in children: Bogalusa Heart Study.

Plasma glucose and insulin levels were determined in a total biracial community of 3313 children, ages 5-17 years. Black children have significantly higher insulin and lower glucose levels than white children of comparable age and sex. Children of diabetic parents have elevated levels of age- and weight-adjusted fasting cholesterol. Moderate tracking (r = 0.31) of glucose levels over a 3-year period was seen. Insulin levels, however, track well (r = 0.36) only in older children (ages 9-14 years at initial examination). Fasting insulin levels are positively related to measures of obesity, systolic and diastolic blood pressure, triglyceride, beta-lipoprotein cholesterol and pre-beta-lipoprotein cholesterol levels. In addition, insulin levels are negatively related to alpha-lipoprotein cholesterol levels. Fasting glucose levels are positively related to systolic and diastolic blood pressure, triglycerides, pre-beta-lipoprotein cholesterol, and obesity levels. The relationship of plasma glucose and insulin levels to the traditional cardiovascular risk factors in children emphasizes the importance of subtle abnormalities in carbohydrate metabolism in the early natural history of cardiovascular disease.

Adolescent↗

Prevention of atherosclerosis in childhood.

Atherosclerosis begins in infancy, with fatty streaks appearing at the age of 3 years and fibrous plaques appearing during adolescence. Fatty streaks and fibrous plaques are related to serum total cholesterol, LDL-C, and systolic blood pressure levels. Children with elevated levels of cholesterol and blood pressure track (i.e., maintain elevated levels over time) and are candidates for premature coronary artery and cerebrovascular disease, especially if there is a positive family history of premature CVD. Screening for CVD risk factors in children is rapid, simple, inexpensive, and effective, with tremendous potential to prevent future adult CVD. At their annual physical examinations, children 5 years of age or older should have careful blood pressure measurements by two observers, and determinations of serum total cholesterol levels. Levels should be plotted on standard percentile grids (Figs. 5-7) in the child's permanent medical record. Those with persistently elevated levels of blood pressure and/or serum LDL-C require nonpharmacologic intervention initially, but may require antihypertensive or antilipid medication if unresponsive to behavioral modification for diet, physical activity, and cigarette smoking. Pediatric health professionals can play vital roles in primary prevention and reduction of adult CVD.

Adolescent↗