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Studies of the pathobiologic consequences of high blood pressure in childhood, as well as those following blood pressure levels into young adulthood, indicate that early intervention in the natural history of essential hypertension is warranted. In an exploratory study of the concept, 95 children out of 1604 (aged 8 to 18 years), who persistently scored higher than the 90th percentile for blood pressure over a 4-month period, considering the race, sex, and height of the children, were studied. Five series of replicate measurements with 30 total observations were obtained. Children with evidence of secondary hypertension were excluded. The study children were randomly divided into treatment (n = 48) and high-comparison (n = 47) groups. Treatment consisted of low-dose combined drug therapy (propranolol and chlorthalidone) with an educational program directed towards hypertension and dietary and exercise modification. Monthly follow-up was continued for 30 months. Significant systolic (-3.59 mm Hg) and diastolic (-1.73 mm Hg) changes were noted up to 30 months (p less than 0.05) with minimal side effects. Furthermore, analyses suggested that the blood pressure change, at least in the first month, was mostly attributable to drug therapy. Moreover, the mechanism of blood pressure change appeared to be race-specific, with whites having pulse rate changes and blacks having significant weight changes, which were associated with blood pressure change. This trial shows further research is warranted to determine optimum approaches for early treatment of essential hypertension to prevent future hypertensive disease.

Resting heart rates were ascertained during the 1978-1979 school year in 3590 children aged 5-17 years in the biracial geographic population of Bogalusa, Louisiana. These rates were found to be relatively independent of the method of measurement, whether supine by physician's stethoscope or dressed sitting radial pulse taken by a nurse, and in either case adhering to a strict measurement protocol. Apart from the known influences of age and sex, the authors found a small but consistent racial influence, with whites having 3-4 beats/min higher rates than blacks. Controlling for age, the authors found heart rate to be positively correlated with blood pressure in whites and with subcapsular skinfold thickness in boys. No consistent relation between heart rate and amount of cigarettes smoked was observed. Boys in the upper five percentiles of blood pressure-heart rate ("double") product values were found to have about twice the subscapular skinfold thickness compared to the lower five percentiles. Likewise, boys in the upper five percentiles of subscapular skinfold thickness had significantly increased double products. Since the double product is an index of cardiac oxygen consumption, this finding could point to a possible etiologic link between obesity and chronic cardiac stress in males beyond the mediation of lipoproteins, cholesterol, and diabetes mellitus in contributing to atherosclerotic heart disease, but this issue needs further study. Ascertainment of resting heart rate provides an additional parameter in the study of cardiovascular risk factor variables, in youth as in adulthood, to supplement the natural history of the atherosclerosis-hypertension syndrome with its sequelae.

A model designed as primary hypertension prevention for children ranking high in blood pressure, selected from a total population, was applied to a semirural, biracial community. A Dietary/Exercise Alteration Program Trial (ADAPT), in combination with low-dose medication, was tested on 48 children aged 8-18 years who were randomly selected from 100 children consistently in the upper blood pressure decile. The interactive model a) focuses on a major public health problem that is measurable and modifiable, b) outlines a preventive approach to involve children and parents in establishing healthy life styles, and c) converts community limitations into resources. The comprehensive program was developed to support eating and exercise modifications accepted for hypertension treatment without placing children in a sick role. Sodium reduction, weight control, and regular exercise are the life-style changes promoted. Indicators for evaluating development and implementation of ADAPT are presented. The commitment to written pledges, ie, making simple behavioral changes, had a significant inverse association with post-treatment sodium and energy intakes in regression models that included the child's curriculum and physical activity class attendance. ADAPT represents an initial approach for developing primary preventive treatment of early essential hypertension in a pediatric population.

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.

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.

In preparation for the measurement of blood pressure in children of a total geographic community, several preliminary studies of the validity and reliability of various methods and instruments for indirect blood pressure measurements were performed. These studies included Graeco-Latin Square designs, examination of children in a field setting, and assessments of the replicability of reading automatically recorded blood pressures. Each of the studies was designed to monitor the validity and replicability of instruments, methods, and observers. Controlling for subject, we compute biases due to instrument, method and observer and, where possible, eliminated them in the enusing studies. One automatic instrument, the Physiometrics recorder, was selected and used in conducting epidemiologic studies where it complements the measurements by the mercury sphygmomanometer.

Eighty per cent of all identified children 2 1/2-5 1/2 years old in a total geographic community in Bogalusa, Louisiana, were examined for cardiovascular disease risk factor variables, including blood pressure (BP), anthropometric measurements, and blood lipids. Blood pressure was measured by three instrument types, each with three readings, according to a rigid, randomized design. Results from the three instruments were compared, and potential biases for each instrument are listed. All observations on the children were analyzed by multiple regression with BP as the dependent variable. After controlling for the mood of the child, the authors found that some index of body size was positively related to BP, whereas age, race, and serum lipids were not consistently related. The regressions of blood pressure on height as well as on log weight fit straight lines. These results conform with the findings for the 5- to 14-year-olds in this community. The basal or fundamental reference blood pressure is likely to rise gradually from birth to the age of incipient adult stature, and to be linearly related to height and to log weight. Changes observed over time are needed to relate BP levels in childhood to the early natural history of essential hypertension.

Blood pressure, height, weight, maturation, triceps skinfold thickness, serum lipids, and hemoglobin were measured as risk factors for coronary artery disease in 3,524 children (93% of the eligible population) in Bogalusa, Louisiana. Nine blood pressures were taken on each child by trained observers with mercury sphygmomanometers (Baumanometer) and Physiometrics automatic recorders in a rigid randomized design in a relaxed atmosphere with other children present. The pressures observed were low compared to reported data. Black children had significantly higher blood pressures than white children. This difference, starting before age 10, was largest in the children in the upper five percent of the pressure ranks. Stepwise multiple regression analysis revealed that this racial differnce was significant when measured by an automatic recorder. Body size, expressed by height and by weight/height3 index, was a strong determinant of blood pressure level. Other positive determinants were blood hemoglobin and external maturation.

The onset of essential hypertension early in life is indicated by the high tracking of blood pressure during adolescence; intervention in adults with mild hypertension has been found successful. How, then, can high blood pressure levels in children be modified to prevent early hypertensive cardiovascular disease in adulthood? In an entire biracial town (population 9000) we surveyed 1604 (89%) of all children aged 8--18 years for blood pressure and reexamined those in the upper decile of mean blood pressure (for each race, sex, and height) on three additional occasions. On each examination nine blood pressures were taken by trained observers. All children consistently in the top decile were randomly allocated into either a treatment (n = 50) or comparison (n = 50) group. These two groups and an additional midrange blood pressure comparison group (n = 50) were followed regularly using school facilities including community and school programs. Treatment consisted of 1) dietary guidance; 2) modifications of school lunches and snacks with healthy substitutes; 3) parental involvement; 4) a low dose diuretic and beta-antagonist given by usual standards. All study groups were monitored for blood pressure in a blind manner. In 6 months of observation, blood pressure in the treatment group remained 5 and 3 mm Hg (systolic and diastolic) less than controls (p less than 0.001 and p less than 0.01). An orchestrated community-wide attack on early-stage hypertension is feasible and seems to offer exciting potential for prevention of early hypertensive disease.

Body height and body mass as determinants of basal blood pressure in children--The Bogalusa Heart Study. Am J Epidemiol 106:101-108, 1977. Risk factor variables for coronary artery disease were measured in a total biracial community study of 3524 children, ages 5-14 years. Anthropometric variables, serum lipids, and blood pressure (BP) were measured in a rigid randomized design. Blood pressure data were obtained with an automatic recording instrument that avoids excessive pressure readings in obese children by the use of an over-sized arm cuff bladder with a built-in infrasonic transducer. By reducing the anxiety of the child and by taking multiple readings, pressures were obtained that approached published basal levels. A multiple regression analysis showed that all measured variables could account for 39% of the systolic BP variation. Major determinants were based on weight (W) and height (H). The BP levels, when related to H and to a weight-height index (W/H3), suggest a strong influence of H and an additional influence of W/H3 on BP, both consistent and proportionate over the entire ranges of H and W/H3. The total spectrum of observed correlates of BP, resulting from the multiple regression analysis, suggests that the BP measured under basallike conditions increases as the child grows and is proportional to lean body mass and total body mass. Practical criteria for evaluating abnormal blood pressure levels in children should be based on normative values derived from body weight and body height rather than from age.

Eighty per cent of all identified children 2 1/2-5 1/2 years old in a total geographic community in Bogalusa, Louisiana, were examined for cardiovascular disease risk factor variables, including blood pressure (BP), anthropometric measurements, and blood lipids. Blood pressure was measured by three instrument types, each with three readings, according to a rigid, randomized design. Results from the three instruments were compared, and potential biases for each instrument are listed. All observations on the children were analyzed by multiple regression with BP as the dependent variable. After controlling for the mood of the child, the authors found that some index of body size was positively related to BP, whereas age, race, and serum lipids were not consistently related. The regressions of blood pressure on height as well as on log weight fit straight lines. These results conform with the findings for the 5- to 14-year-olds in this community. The basal or fundamental reference blood pressure is likely to rise gradually from birth to the age of incipient adult stature, and to be linearly related to height and to log weight. Changes observed over time are needed to relate BP levels in childhood to the early natural history of essential hypertension.

The relationship of dietary K+ with Na+ balance in young normotensives was studied. A, In two biracial communities, all children with specified age were stratified by blood pressure level. Children from selected strata collected 24-h urines on ambulatory basis and provided fasting blood for electrolytes and creatinine determination. For the upper percentile ranks (n = 160), the Na+ and K+ clearances correlated closer in Blacks than whites (r = 0.7 versus r = 0.4, p less than 0.005 for difference). B, To test for a causal effect of K+ intake on Na+ excretion, six white and eight Black young healthy normotensive volunteers took 80 mEq KCl daily in addition to their usual diets. They collected 24-h ambulatory urine and stool samples for 3 base-line days, and 4 days during K+ supplementation. Na+ and K+ intake was monitored daily. Upon K+ supplementation, Blacks showed natriuresis (p less than 0.01), negative Na+ balance (p less than 0.05), and a cumulative K+ balance more positive than whites (p less than 0.0001 versus p less than 0.05). Dietary K+ enrichment could affect Na+ balance.

Publisher Summary The question of how changes in behavior can modify the process of atherosclerosis and hypertension during adolescence is practical and important. However, no uniform answers exist to that question. There is an abundance of studies with animals relating nutritional and psychological states to cardiovascular risk factors, but there is a serious question about how applicable those models are for prescribing intervention in the atherosclerotic/hypertensive process. The atherosclerotic/hypertensive process has apparently evolved so recently that even within the human species, blacks and whites have different mechanisms for the development of this process. Inter- and intra-species differences in non-human primates limit the applicability of these studies to cardiovascular disease in man. Further, the limitation of hospital-based studies to symptomatic individuals in later and complicated stages of the process is well known. There is a great need for an epidemiologic approach to cardiovascular disease in man. This chapter discusses nutritional and other behavior associated with increased risk of coronary artery disease and also considers the following four risk factors — obesity, high blood pressure, blood lipids, and blood insulin-glucose.

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.

The relationship between body fat indexes, lipid and lipoprotein levels, and blood pressure was studied in 2230 children, each examined during 1973, 1976, and 1978. The children were grouped with the use of seven percentile (P) intervals of triceps skinfold thickness that were specific for race, sex, and age; cardiovascular risk factor variables were assessed over time. Of the 238 children initially in the lowest P group (less than 15P), 44% remained there, and 65% had skinfold thicknesses below 30P on the three occasions. Of the 352 children in the highest P group (greater than or equal to 85P), who were considered to be very obese, 39% remained at this level while 69% remained at 70P or greater. Of the 366 considered to be obese (greater than or equal to 70, less than 85%P), 38% remained at or above 70P. At baseline, children in the seven groups differed in weight, ponderosity (wt/ht3), systolic and diastolic blood pressures, serum triglyceride levels, and pre-beta- and beta-lipoprotein cholesterol levels. Pairwise comparison of data from children in each of the six other groups with those from children in the middle range (greater than or equal to 40, less than 60P) showed that the obese and very obese children had significantly higher systolic blood pressures (p less than .05), while only those in the highest P group had significantly greater diastolic blood pressures (p less than .05). These differences increased and diverged over time. Those in the obese and very obese groups showed a striking drop over time in alpha-lipoprotein cholesterol levels and increases in pre-beta-lipoprotein cholesterol levels and systolic blood pressure. Triglyceride levels decreased over time for the lowest and middle range groups but remained at higher levels in obese and very obese children. There was a strong tendency for tracking (remaining in the same P group over time) in lean, obese, and very obese children. Those who tracked showed definite differences in risk factor variables at the baseline level and over time when compared with the middle range group. Since consistent obesity in early life enhances cardiovascular risk, the measurement over time of skinfold thickness in children is a useful method to detect the potential for adult cardiovascular disease.

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.

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.

• There is evidence that atherosclerosis, coronary artery disease, and essential hypertension begin early in life. The Bogalusa (La) Heart Study has examined cardiovascular risk factors and their determinants during the pediatric age span in a total community study. Reliable measurements were obtained and then analyzed to identify "tracking" of risk factors over time and clusters or aggregations of various risk factors at high levels. Serum lipoprotein levels, obesity, BP, and plasma insulin levels were all correlated after a glucose load, implying causal interrelationships. Although such relationships are only partly elucidated, the associations potentially enhance premature atherosclerosis. Certain kinds of behavior, for example cigarette smoking and type A behavior, may also contribute to early coronary artery disease. Our observations suggest that practicing physicians should assess risk factors in children and encourage changes in life-style to combat the high incidence of coronary artery disease and essential hypertension in the United States. (Am J Dis Child1982;136:855-862)

Indirect blood pressure (BP) was measured by mercury sphygmomanometer on 3524 children, ages 5-14 years, representative of a defined geographic population. Year 1 to Year 4 correlations ranged from 0.52 to 0.63 systolic blood pressure (SBP) and from 0.23 to 0.45 diastolic 4th phase blood pressure (DBP4). Some 55% of those originally in the upper decile remained in the uppermost two deciles 3 years later. All children ages 5, 8, 11, and 14 years were reexamined annually, and the mean year-to-year standard deviation (SD) within the child was computed to be 5.5 mm Hg SBP and 5.9 mm Hg DBP. After 3 years, for all available children (n = 2601) the age-specific cross-sectional SD was found to be 8.7-9.7 mm Hg SBP and 7.6-8.0 mm Hg DBP. These data enabled us to quantify the regression to the mean due to within-child variation for the uppermost and the lowest decile BP, using the Gardner-Heady model. These children had an average BP at examination that differed from the expected level (adjusting for regression to the mean due to within-child variation) by 1 mm Hg SBP and DBP. Quantification of the degree to which children's BP "tracks" is important for early diagnosis and intervention in high BP.

To investigate whether cuff bladder dimensions relative to the length and circumference of the upper arm affect the outcome of epidemiologic blood pressure surveys, multiple observers took multiple measurements on each of 92 grade school children from Franklinton and 351 children from Bogalusa, Louisiana. For the present study, the broad, hard surrounding cuff of the Physiometrics blood pressure recorder using a transducer embedded in the ample cuff bladder gave "true readings." Baumanometer readings were performed using standard cuff sizes selected according to currently recommended criteria. "Excess pressure reading" equal to mean Baumanometer reading minus mean true reading. "Deficient cuff bladder length" equal to percentage of upperarm circumference not covered by the rubber bladder. Pearson correlation coefficients for the two groups of children supported the hypothesis (at the 5% level of significance) that deficient cuff bladder length is associated with excess pressure reading. The relevant correlation coefficients for the two groups of children were 0.18 and 0.31 (systolic pressure) and 0.24 and 0.19 (diastolic pressure). In addition to sufficient cuff width, the complete surrounding of the entire arm circumference by the rubber bladder is recommended for epidemiologic studies of children.

Essential hypertension, a highly prevalent and devastating disease, likely begins in childhood, and presumably might respond at this stage to general preventive measures. The problems encountered in the recording of reproducible blood pressure levels are largely of a quantitative nature, and involve instrument validity, observer (examiner) training, and the interaction between the child and the physician's office environment. The problems of early diagnosis of hypertension are related to the lack of long-term observations of children. Population percentiles of normal blood pressure values could aid in the early diagnosis of hypertension. For this purpose the method of blood pressure measurement in the physician's office has to be strictly comparable to methods employed in accumulating the percentile or reference observations. Repeated measurements under basal-like conditions are advised, and the weight or height of the child is more important for standardization than is age.

BP was measured in 440 children followed longitudinally from birth to 7 years of age in Bogalusa, LA. Levels, trends, and determinants of BP were evaluated in this newborn cohort. Both systolic and diastolic BP levels remained relatively constant between the ages of 6 months and 7 years. BP levels varied between the different instruments, and differences were also noted between measures obtained using the same instrument before and after venipuncture. White children were noted to have slightly higher levels of systolic and diastolic BP pressure at 6 months and 1 year of age, even after adjustment for body size. Significant prediction of year 7 BP rank occurred as early as 6 months of age for systolic and at 1 year of age for diastolic BP levels. Body size was inconsistently related to BP levels from ages 6 months through 4 years, but the relationship was stronger and more consistent with changes in body size. Of interest is the relatively constant levels of indirect BP during this period of rapid growth, as measured by currently available instruments. These data emphasize the importance of cardiovascular risk factor measurement during early life and of the need to improve methods of indirect BP measurement in infancy.