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

Racial Differences of Parameters Associated With Blood Pressure Levels in ChildrenThe Bogalusa Heart Study G. S. Berenson, A. W. Voors, L. S. Webber, E. R. Dalferes, Jr., and D. W. Harsha 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 l-2 yr after initial observation for the following: (1) a physical examination and urinalysis to exclude secondary hypertension; (2) 24hr urine sodium, potassium, plasma renin activity, and serum dopamine phydroxylase; (3) l-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 restingsupine 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 @-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 l-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.

I

T IS WELL RECOGNIZED that there are significant racial differences in the prevalence of hypertension. In the United States, not only is hypertension more prevalent in black than in white people but it is also more severe.“’ The prevalence in blacks is approximately twice

From the Departments of Medicine and Public Health and Preventive Medicine. Louisiana State University Medical Center, New Orleans, La. Receivedfor publication January 22. 1979. Supported in part by funds from the National Heart, Lung, and Blood Institute of the USPHS. Specialized Center of Research-Arteriosclerosis Grant HLI5103. Address reprint requests to G. S. Berenson. M. D., L. S. U. Medical Center, 1542 Tulane Avenue, New Orleans. La. 70112. 0 I979 by Grune & Stratton, Inc. 0026-0495/79/2812-0006$02.00/0

1218

that of whites. In addition to the increased prevalence, reported death rates for hypertension and hypertensive heart disease indicate this to be an even more severe disease in black individuals. Mortality rates are reported approximately three times higher in blacks. From such data it becomes evident that in blacks, hypertension occurring at a relatively young age carries an extremely high risk. We are just now beginning to study the onset of essential hypertension as it begins in childhood and the early natural history of essential hypertension3 Although blood pressure levels in black adults have been clearly established to be higher than in whites in the general population, only a limited amount of information on racial differences has been published on children. Our studies indicate that in children as well, upper-percentile blood pressure levels are higher for blacks than for whites.4 In an effort to study the early onset of essential hypertension, observations were made on a selected sample of children. Racial differences were detected that might contribute to a better understanding of the early natural history of hypertension and of the greater severity of this disease in black people. In 1973 we began the Bogalusa Heart Study on some 5000 children in a geographically defined biracial population of 22,000. A considerable amount of information has now been published from the cross-sectional study conducted in 1973-l 974.“’ Subsequently, special studies related to hypertension have been conducted on children selected by their levels of blood pressure. Summary of Anthropometric, Lipid, and Blood Pressure Diflerences in the Total Population of Children For the total cross-sectional study of 3524 children, ages 5-14 yr, we described marked differences in triceps skinfold, which was consistently thicker in whites than in blacks for each year of age, both for boys and girls.’ Body weight was not higher in whites than in blacks

Metabolism, Vol. 28, No. 12 (December), 1979

RACIAL DIFFERENCES IN CHILD HYPERTENSION

1219

when either age or body height was controlled. Upper arms were slightly but consistently longer in blacks than in whites controlling for age. To confirm the anthropometric differences between the races, we conducted a series of underwater weighings of volunteer children ages 6-16 yr.9 Converting body density into percent body fat,‘” we found, as shown in Fig. 1, that whites had on the average more relative body fat than blacks in boys (22% versus 17%) as well as girls (28% versus 24%), in spite of approximately equal total body weight. Consistent racial differences in serum lipid and lipoprotein fractions were also observed in the total child population of Bogalusa.5*6 Serum triglycerides and pre-P-lipoprotein levels were higher in whites than in blacks for each year of age. Conversely, cu-lipoprotein levels were consistently higher in blacks than in whites, which accounted for slightly higher serum total cholesterol levels in black children. However, a closer relationship between fasting lipids and lipoprotein serum levels and measures of obesity, like triceps skinfold thickness, was observed in whites than in blacks. Racial differences for cardiovascular risk factor variables were observed in blood pressure measurements also. Using the automatic blood pressure recorder, we found small but consistent systolic and diastolic (fourth Korotkoff phase)

loo-

racial differences for each year of age, the blacks having the higher pressures. The average agespecific differences between the races was 1.9 mm Hg systolic and 1.6 mm Hg diastolic. This difference was notably greater in the upper 5% of blood pressure levels for each age and was also detected by indirect measurements with the mercury sphygmomanometer. MATERIALS

AND METHODS

Study Population During the 1973-1974 school year, 93% of all Bogalusa children ages 5-14 yr were examined. Of the 3524 examinees, 63% were white and 37% black. Sitting and relaxed blood pressure readings were obtained by three observers: two used a mercury sphygmomanometer and one used an automatic blood pressure recorder (Physiometrics, Sphygmetrics, Woodland Hills, Calif.). Each observer measured systolic and diastolic (fourth phase) pressures three times.

Sample Selection Based on Blood Pressure Levels In a statistical analysis, three age groups of children were considered; 6-7 yr, 9-10 yr, and 12-l 3 yr of age. In each of these groups the four race-sex combinations were considered separately, resulting in 12 subgroups. For each subgroup, the rank of the median diastolic blood pressure value by each observer was assessed for each child, and these three ranks were summed. The resulting summed rank scores formed the basis for a stratified random sampling. sexand racespecific, with weighting of the extreme pressure samples. In this manner a sample of 368 children was drawn for an

I

I

I

100

101

1.02

go807060-

Fig. 1.

Cumulative frequency of density and

percent body fat by race and sex in 242 volunteer children in Bogalusa, 1975-1976.

DEWS;O%

sow FAT 500

1

450

401

353

1.03 306

104 260

I

105

106

107

108

I

I

I

I

12.6

83

21.4 170

108muco 1

41 (%I

1220

BERENSON ET AL.

amplified reexamination, grouped in five strata labeled from 1 (low blood pressure) to 5 (high blood pressure), representing all children of the extreme 2% for strata 1 and 5, 70% of the next 4%-9% for strata 2 and 4, and 37~8% of the remaining children for stratum 3, to obtain equal numbers of children for each of the four race-sex groups. The reexamination took place 1-2 yr after the original survey, with 314 children still residing in the community: 53 children had moved out of Bogalusa and one had died. Of those remaining in Bogalusa, 32 refused participation and 4 were unavailable. Thus, 278 (75% of those selected but 89% of those available) were reexamined. Based on findings of proteinuria, abnormal formed elements in the urine, and positive urine cultures, six children were eliminated from the study; this was to exclude children who may have had higher blood pressure levels secondary to renal disease. Among the sample of children for the special study there was balance in age, race, and sex within each of the blood pressure strata.

Twenty-Four-Hour

Urine Collections

Urine was collected on an ambulatory basis during two 24-hr periods immediately preceding a physical examination and venipuncture. Direct contact with parents and teachers, oral and written instructions, provision of nonobstrusive collection equipment, mailed reminders, and home and school visits were all part of an elaborate and rigidly protocol&d program. Feedback to the children on the completeness of urine collected in the first 24-hr period sometimes resulted in improved yields during the second 24-hr period. Plastic containers for urine collection contained 5 ml 1N HCl and 150 mg thymol crystals.

General Flow of Examination The children underwent a series of procedures during an entire morning of examinations. The children reported fasting at 8:00 a.m. and were kept standing and occupied for the next l-l’/2 hr. Their urine collection bottles were received and they were interviewed on completeness of the urine collection and on the details of their fasting. The examination consisted of five parts: Anthropometry. A series of skinfolds and height and weight measurements were performed. These measurements were obtained according to a rigid protocol by the same observer in all cases, with the purpose of estimating total body fat and lean body mass from densitometric studies?,“’ Blood and urine laboratory analyses. Several blood samples were taken from each child between 9:00 and 9:30 a.m. for multiple laboratory analyses. These included uric renin,12 dopamine B-hydroxylase,” glucose, and acid,” insulin (see following). In addition, electrolytes. Na+, K’ Ca++, Mg+‘, and creatinine14 were determined on blood and urine samples (Table 1). Physical examination and urinalysis of a midstream, clean-catch sample. A physician examined each child including a urine sample in an attempt to exclude children with secondary hypertension. The urinalysis consisted of standard dipstick techniques, microscopy of a centrifuged sediment, and culture for microorganisms. Oral glucose tolerance tests. After venipuncture for fasting blood, the child drank 1.75 g glucose/kg ideal body weight as determined by age, height, and sex according to the

standards published by Faber.” A second venipuncture occurred 1 hr after the glucose intake. Plasma glucose was assessed by the method of Hultman’6 as modified by Hycel, Inc. (Houston, Tex.), and plasma insulin was assessed by the radioimmunoassay method of Yalow and Berson,” using the Phadebas Insulin Test Kit (Pharmacia Laboratories, Piscataway, N.J.). Blind duplicate samples were analyzed in order to assess the intralaboratory measurement error (standard deviation, absolute and relative to mean value). For plasma glucose the measurement error was 7.4-9.0 mg/dl (7.9%8.3%), and for plasma insulin it was 5.2-12.5 &U/ml (41% 20%). respectively, for the fasting and the I-hr determinations. Cardiovascular response tests. The repeated resting blood pressure measurements are described elsewhere.’ Prior to the series of response tests, the child was taught how to use a handgrip, a 19117M Smedley hand dynamometer (Stoelting, Chicago, Ill.), according to the manufacturer’s manual, and a maximum voluntary contraction (MVC) was assessed in three trials. Each child was randomly allocated to one of two teams of four nurses who performed all cardiovascular response tests in sequence on that child before proceeding with the next child allocated to that team. At the beginning of the test series, the child was connected to electrocardiographic limb leads for recording heart rate. For blood pressure measurements, a Whittaker B250L Sphygmostat (Waltham, Mass.) was used. During the first test for orthostatic response, the child lay supine on an examining table for at least 4 min and then stood up at a signal. A handgrip test followed in which the child sat on a chair and squeezed the handgrip for 3 min at 20% of his MVC; after resting for 3 min the child squeezed the handgrip for 2 min at 30% of MVC. The last response test was a cold pressor test in which the right hand was submerged in ice water for 1 min while the child was seated.‘* Blood pressures and heart rates were measured at I-min intervals during the series of tests.

Statistical

Analyses

In the statistical analyses, data from boys and girls were combined when analyses of the separate sexes showed similar results. In some presentations, strata 1 and 2 were combined to form the “low” stratum and strata 4 and 5 to form the “high” stratum. Because of the age-, race-, and sex-specific stratified sampling procedure, the blood pressure strata were similar with respect to age, race, and sex. A three-factor analysis of variance model for unequal size samples was used to test for race, sex, or blood pressure stratum effects.” If a statistically significant three-factor or two-factor interaction existed, then only simple effects were examined for these variables; otherwise, main effects were tested.

RESULTS

Serum and Urine Electrolytes There were no statistical (p c 0.05) differences between race or sex groups for serum electrolytes. With respect to 24-hr urine calcium and magnesium levels, boys excreted more magnesium than girls, and calcium excretion was higher for the whites and in the higher blood

1221

RACIAL DIFFERENCES IN CHICD HYPERTENSION

Table 1. Analysis of Blind Duplicate Laboratory Samples-Bogalusa

Heart Study, 1975-76

Number of Pairs

Original

Blind Duplicate

ErrorCoefflclentof vanat1on* (%I

118

6.3

6.3

19.8

Mean Vanable Plasma renin (ng/ml/min) Serum dopamine &hydroxylase (~mol/min/liter)

133

26.0

26.5

18.3

Serum creatinine (mg/dll

134

0.6

0.6

13.9

Serum sodium (meq/liter)

134

139.6

139.5

0.8

Serum potassium (meq/liter)

134

4.4

4.4

4.9

Serum calcium (meq/liter)

133

4.9

4.9

10.6

Serum magnesium (meq/liter)

133

1.9

1.9

9.0

Plasma glucose (mg/dl) Initial

119

94.1

93.1

7.9

One-hour

117

108.4

108.5

8.3

Plasma insulin (&/ml) Initial

119

12.9

12.6

40.7

One-hour

126

64.1

62.3

19.8

134

4.4

4.4

7.3

Serum uric acid (mg/dl) Urine creatinine (mg/dl) Day 1 School Home

92

107.5

106.3

13.2

132

115.6

116.6

6.8

Day 2 School Home

78

101.6

101.7

12.6

132

119.1

119.8

10.2

Urine sodium (meq/literl Day 1 School Home Day 2 School Home

92

165.0

164.8

5.1

133

166.9

157.7

4.0

78

158.2

158.6

5.9

135

162.3

163.2

5.5

‘By blind duplicate study.

pressure strata. These differences persisted after adjusting for body surface.14 There was a marked difference in potassium excretion between the races. The results of urine sodium and potassium excretion by blood pressure strata are shown in Table 2. The black children excreted K’ on the average (+ 2 SE) 28 + 2 meq/24 hr and the whites 39 + 4 meq/24 hr (t test, p < 0.0001). The racial difference in urinary potassium excretion occurred consisTable 2. Twenty-Four-Hour Urine Sodium and Potassium by Race and Blood Pressure Stratum in Children, Ages 7-15 Yr-Bogalusa

Heart Study, 1975-1976 (N = 249) BloodPressureStratum

Race

Electrolyte Na’ K+

l/J <

Mediumt

106 + 13

Black

97 + 12

White*

39 * 4

34 2 7

42 + 7

Black*

26 f 3

27 + 4

29 * 5

mean ‘+ 2 SE

98 r 17

Hight

White

0.0001.

tmeq/liter.

Lowt

103+

17

109 + 14 115&

18

tently in all blood pressure strata and is unlikely to be due solely to a lower potassium intake by black children. In a 24-hr dietary recall survey among a 50% random sample of all 10-yr-olds in this community,* we found mean (+ 2 SE) daily potassium intakes of 2.22 + 0.18 g (97 + 8 meq) in whites and 2.26 it 0.25 g (98 f 11 meq) in blacks. The relationship between sodium excretion and blood pressure as measured on the same day was explored as follows. In the population from which the present sample was drawn we found that height and weight are strong correlates of blood pressure.” In the present study we observed that sodium excretion is highly correlated with weight or body surface. In order to avoid spurious correlations between sodium excretion and blood pressure, we adjusted 24-hr urine sodium for body surface, and made scattergrams of these values with blood pressure, separately for the three blood pressure strata, each

1222

BERENSON ET AL.

Table 3. Plasma Renin Activity (ng/ml/min. in Children. Ages 7-15

Mean -c 2 SE). by Sex, Race, and Blood Pressure Yr-Bogalusa

Stratum

Heart Study 1975-1976

(Al = 272) Blood Pressure Stratum

sex BOYS

Girls

1 (Low)

2

White

5.7 + 1.7 (8)”

7.1 ‘- 1.7 (15)

6.6 I

1.9 (15)

7.6 + 2.1 (14)

8.6 f 2.4 (9)

Black

6.1 + 3.1 (7)

6.9 t 2.2 (16)

4.2 k 1.1 (21)

4.1 ? 1.3 (18)

3.7 f 2.5 15)

White

7.4 f 1.1 (9)

6.5 r 1.3 (14)

5.9 ? 1.6 (16)

7.7 + 2.3 (17)

8.0 f 2.4(11)

Black

3.5 + 2.0 (6)

6.2 + 1.9 (19)

5.0 * 1.2 (19)

7.0 r 2.1 (15)

4.5 f 1.1 (4)

Race

3

4

5 (High)

*Sample size in brackets; 14 children were not included due to missing data.

for white and black children (these scattergrams are not reproduced in this paper). We observed a general tendency from negative association in the low blood pressure stratum toward positive association in the high blood pressure stratum; this tendency appeared to be stronger in the blacks. Because of the design of sampling of children for blood pressure levels, however, we were unable to probe this observation by appropriate statistical tests.

as is found in adults since the children were not urged to achieve dietary values lower than 100 meq/24 hr.14 Serum Dopamine P-Hydroxylase

The serum DPH levels are given by race, sex, and blood pressure stratum in Table 4. Mean DPH levels are consistently lower in blacks (p < 0.0001). No sex differences were noted, nor differences in DPH levels comparing blood pressure strata. DPH levels tended to increase with age (p < 0.005). D/3H levels are plotted against renin levels for each race in the high blood pressure stratum in Fig. 2. A marked racial difference is noted with the absence of high renin-high DPH children among blacks, indicating a relationship opposite to that in white children. This racial difference of DPH has also been reported by Horwitz et al.*’

Plasma Renin Activity

Average plasma renin activity was 7.1 ng/ml/hr for whites and 5.3 ng/ml/hr for blacks. This racial difference is statistically significant (p < 0.0002). The plasma renin activity is given by race, sex, and blood pressure stratum in Table 3. No sex differences were observed (p > 0.05). The racial difference is noted in the middle strata and especially in the combined high blood pressure strata. Renin levels within races were not significantly different comparing blood pressure strata, although there is a slight decrease in renin for black boys in the high blood pressure strata (race versus blood pressure stratum interaction, p < 0.05). A similar slight decrease in renin for blacks is noted in the older compared to the younger age groups.14 The studies of plasma renin activity by urinary sodium excretion showed no trend such Table 4.

Serum Dopamine &Hydroxylase

(pmollminlliter,

in Children, Ages 7-15

(D@H)

Plasma Glucose and Insulin Levels

Fasting plasma glucose levels were higher in whites than in blacks (p < 0.005). Plasma I-hr glucose levels are given by race and by blood pressure stratum in Fig. 3. Although girls had higher values than boys, especially for whites, sex differences were not remarkable; therefore, further computations were performed combining both sexes. There was a significant interaction between the effects of race and blood pressure Mean f 2 SE) by Sex, Race, and Blood Pressure Stratum

Yr-Bogalusa

Heart Study, 1976-l

976

(N = 272) Blood Pressure Stratum Sex

Race

1 (LOW)

2

3

4

5 IHIgh)

Boys

White

37 + 6 (9)’

29 ? 7 (16)

32 + 8 (16)

28 t 7113)

33 + 8 (9)

Black

26 + 13 (8)

23 -c 5 (17)

17 + 5 (21)

24 + 6 (20)

23 + 13 (5)

Girls

White

30 t 12 (9)

25 + 8 (16)

27 + 8 (17)

29 + 7 (17)

35 f 6(11)

Black

17 + 7 (6)

20 + 7 (20)

22 + 5 (20)

22 r 6 (16)

19 + 18(4)

‘Sample size in brackets; two children were not included due to missing data.

RACIAL

DIFFERENCES IN CHILD HYPERTENSION

4

1223

BLACKS

WHITES I

I

l

0

.

a

@ IN UPPER 10

I

PERCENTILES 1 (REEXAYINATION)

s I

0 2

I -I

l-

0

10

li II

I

I

20

30

I

40

I

50

60

I

1

0

i

l

lb

I

20

I

30

4b

5b

I

t

60

SERUM DOPAMINE-j3-HYDROXYLASE, pmol/min/L Fig. 2. Scattergrams of plasma renin activity compared to serum dopamine &hydroxylase for the high blood pressure stratum in whites and blacks. Median values for children of all strata combined are represented by dotted lines. The preponderance of children with combined high renin and high D@H. expected in high blood pressure strata, is lacking among the blacks. Children whose diastolic mercury sphygmomanometer pressure (fourth phase) as measured during reexamination was in the upper 10% of his/her age and race group are marked (0). They conform to the above conclusion.

strata on 1-hr glucose level (p < 0.01). For white children the plasma glucose levels increased from the low to the high blood pressure strata; the slope of the linear regression of l-hr glucose on blood pressure stratum was significantly positive (p < 0.05), but for the blacks this regression slope was not significantly different from zero (p > 0.05). Fasting plasma insulin levels were slightly lower in boys (12 pU/ml) than in girls (15 &l/ml). N o consistent racial differences or trends over blood pressure strata were noted. Plasma 1-hr insulin levels were lower in boys (45 pU/ml) than in girls (78 $J/ml). There was no difference between the races. There was a significant three-way interaction between the effects of sex, race, and blood pressure stratum on I-hr insulin level (p < 0.05). A trend in plasma insulin over the blood pressure strata was observed only for the white boys, where the insulin levels increased from the low to the high blood pressure strata; this positive trend remained after adjustment for body weight (p .C 0.005 in test for linear regression). In order to obtain an index of peripheral insulin resistance, we multiplied the 1-hr glucose with the I-hr insulin level for each child.** This procedure is consistent with the mathematic mode1 proposed by Ackerman et al.*’ There was a significant three-way interaction between the effects of race, sex, and blood pressure stratum on peripheral insulin resistance (p c 0.05). For the white boys the resistance index rose more

iiWhites Blocks

Low

BLOOD

Medium

PRESSURE

High

STRATUM

Fig. 3. One-hour plasma glucose level (mean + 2 SE), by race and blood pressure strata in children ages 7-15 yr. Two out of 272 observations were excluded due to missing data. It might be noted that children in the highest blood pressure stratum were heavier than those in the lowest (by 15 kg on the average). but a similar weight-glucose level relationship was not seen in black children in this stratum.

BERENSON ET AL.

1224

mv

Medium

kdium

BOYS

GIRLS

Index of peripheral insulin resistance (mean + 2 Fig. 4. SE) by race, sex, and blood pressure stratum. index = GLUC x INS, where GLUC is 1-hr plasma glucose level (mgldl) and INS is 1-hr plasma insulin level f&f/ml). Whites appear to have a higher resistance than blacks; in boys. this difference appears to be most marked in the high blood pressure stratum.

from the low to the high blood pressure strata than in any other race-sex group (Fig. 4). We also observed a consistent and strongly positive correlation with body weight, and in the white children this correlation was not eliminated by controlling for age. Although such a relationship is well known in adulthood, the relationship of body weight and carbohydrate intolerance as a potential cardiovascular risk factor is apparently already developing during childhood.

yields blood pressure levels comparable to basal levels. These measurements were repeated on the selected sample of children and the results of the measurements showed that after 1s-2 yr, each stratum maintained its rank for whites and for blacks. Mean values for stratum 5 were 17 mm Hg higher than for stratum 1, both systolic and diastolic. In the upper percentiles, blacks had higher blood pressures than whites.14 The cardiovascular response tests were performed at the end of the sequence of examinations. Resting supine systolic blood pressures of black boys in the high blood pressure stratum had higher systolic levels than any other group. Resting supine pulse pressures were highest in the black boys, especially in those of the high blood pressure stratum. In the black boys of the high blood pressure stratum (N = 25) the various resting systolic blood pressures were negatively related to the plasma renin activity, with correlation coefficients ranging from -0.34 (p > 0.05) to -0.65 (p < 0.001).24 Resting supine heart rates are presented for each race and sex by blood pressure stratum in Fig. 5. There is a marked positive increase in resting heart rate over the blood pressure strata for whites, but this was not noted for blacks

Serum Uric Acid

Serum uric acid levels (mean f 2 SE) were 4.7 f 0.2 mg/dl for boys and 4.1 + 0.2 mg/dl for girls. There were no obvious differences between races or between blood pressure strata. Resting Blood Pressure and Heart Rate

In an attempt to obtain reproducible blood pressure observations in the cross-sectional study examinations, the children underwent repeated sitting blood pressure examination in an anxietyfree, relaxed atmosphere according to a protocol described earlier.4 In our hands the methodology

Low

Medium BOYS

t

h

Low

Irrledium b GIRLS

Resting-supine heart rate (mean f 2 SE) by Fig. 5. race. sex, and blood pressure stratum in children ages 7-15 yr. For white boys and girls the heart rata is increased in the high blood pressure strata. This is not the case for blacks.

1225

RACIAL DIFFERENCES IN CHILD HYPERTENSION

(race versus blood pressure p < 0.0005).

stratum

interaction,

Cardiovascular Response Tests For the combined races and sexes, resting and maximal values for blood pressure levels showed a rising trend among increasing blood pressure strata. This trend was generally less marked for resting and stressed heart rates. Responses in blood pressure level and heart rate to the stress tests did not show a trend over the blood pressure strata. In a multiple regression analysis in which the systolic and diastolic blood pressure response and the heart rate response were the respective dependent variables and race, sex, and blood pressure strata the independent variables, the regression on high and low blood pressure strata was not statistically significant, with minor exceptions.24 Like the resting supine systolic levels, the maximal stressed systolic levels showed significant positive trends over the blood pressure strata only for black boys (three-factor interaction, p < 0.005). For black boys in the high blood pressure stratum, the systolic levels in the orthostatic and cold pressor tests were significantly higher (p < 0.05) than in each of the other groups. In general, results from stress testing did not show a trend in the stress-caused increases of cardiovascular parameters among the blood pressure strata: children in the high blood pressure strata did not show a greater increase than those in the low strata. Marked trends in systolic and diastolic pressure levels among the blood pressure strata were already present during the resting, sitting examination. Systolic as well as diastolic levels with the average difference of 17 mm Hg between highest and lowest blood pressure stratum reflected the “tracking” of blood pressure in these children from the first observation to the second, l-l ‘/zyr later. The black boys of the high blood pressure strata showed higher resting-supine and stressed systolic blood pressure levels than any other group. Their resting pulse pressures correlated negatively with the plasma renin activity, which was on the average very low in this group.25 In the high blood pressure strata, sitting and relaxed blood pressure levels for black children were positively associated with 24-hr sodium.

DISCUSSION

The nature of racial differences in essential hypertension observed in adults is not clear. Since it is suggested that primary hypertension begins early in life, we attempted to distinguish genetic from environmental causes by investigating children in a biracial community at an age when the disease and end-organ damage are less likely to be established. In our original cross-sectional study we found higher blood pressures in blacks than in whites, notably so in the higher blood pressure strata.4 This observation is particularly important in a consideration of high blood pressure levels and more hypertensive disease in black adults. One major factor in causation of hypertension concerns high dietary sodium. Gleibermann26 surveyed the literature on the relationship between sodium intake and blood pressure in black communities and found a positive association in a composite scattergram. She proposed, as Helmer2’ did previously, an adaptive survival advantage for the genetic trait to conserve human body sodium in black ancestors by preventing them from hyponatremic collapse while losing sodium through sweat and laboring in the heat on a low-sodium diet. In normotensive adults, a sodium excretion in response to a sodium load was found to be slower in blacks than in whites.** The possibility of an increased sodium sensitivity in the upper blood pressure percentiles of black children deserves consideration in a rationale of preventing the expression of hypertension in large numbers of black adults. Significant hormonal differences are found in black children compared to white children. which suggests that mechanisms for blood pressure control have racial differences (Table 5). Although neural and adrenergic influences occur in both races, comparable dietary sodium exposure may have a greater detrimental effect in blacks. The possible reduction in renal potassium excretion by blacks may be related to their known relative decreased sodium excretion under a sodium load.** One possibility would be a genetically determined difference in molecular interaction controlling sodium, potassium, and hydrogen exchange in the renal tubules. Luft et al.,*’ although using a different experimental model, arrived at a similar conclusion. Higher resting-supine systolic blood pressure

BERENSON ET AL.

1226

Table 5. Racial Differences

Related to Blood Pressure

of Children: Higher Values for Characteristics Whites

Blacks All blood pressure strata

Percent body fat Plasma renin activity Serum dopamine b-hydroxylase (Dfil-0 Twenty-four-hour urine K+ Fasting serum glucose High blood pressure strata Resting heart rate Renin activity and DPH combined One-hour serum glucose

Sitting blood pressure levels Positive association of 24-hr urine Na+ versus sitting blood pressure Systolic blood pressures in boys Negative association of plasma renin versus systolic blood pressures (black boys only)

levels and sitting systolic pressure under stress in black boys compared to black girls and white children in the high blood pressure stratum may be an early parameter of hypertension. The blood volume, presumably high through large lean body mass, may be enhanced by sodium retention, possibly through action of testosterone or androgen, which are sodium retaining.29 One main finding of this study is the low renin activity of blacks, especially boys, in the higher blood pressure strata. In young black adults with a preponderance of low renin hypertension, hypertension has been described.30 Coupled with our other studies that indicate blood pressure tracking occurs in childhood,3’ this finding may suggest that the low renin activity may be a characteristic of a group of young black children who will become hypertensive as adults, or it may represent hypertensive disease already present in black children. Brunner et al.30 reported an excess of low-renin type hypertension among young adult black hypertensive patients, which may relate to the reported slower excretion after sodium loading by blacks than by whites.28 The high 1-hr glucose levels in white relative to black children, especially in the high blood pressure strata, may be reflecting racial differences in body fat and in an interface in lipidcarbohydrate metabolism, since racial differences in lipid levels have been reported for the total study population as summarized herein.‘16 Even though we did not find a significantly

positive correlation between I-hr glucose levels and resting blood pressures taken on the same day after controlling for body weight (data not presented in this paper), the possibility of an influence of blood glucose levels on the blood pressure of some children cannot be easily dismissed. Florey et aL3’ reported a positive correlation between postprandial blood glucose and blood pressure in white children and this relationship is well known in white adults.33 Oberman et al.,34 Paffenbarger et al.,35 Frohlich et al.,36 and Kahn et al.” have found that high heart rate is predictive of high blood pressure. Apparently, this may be true in early stages, primarily for white individuals. Weiss et that a higher a1.j’ have recen tl y indicated cardiac index positively related to heart rate may precede early hypertension with an increased peripheral resistance accompanied by a lowered cardiac output to normal ranges. The studies by Guyton et al.39 on the importance of blood volume and cardiac output in the regulation of blood pressure, the early hemodynamic changes of heart rates and cardiac output in early hypertension,-‘* the variability of plasma excretion,40 a renin activity3’ and aldosterone relationship of carbohydrate intolerance to hypertension,32,33 and the racial differences related to blood pressure4’ all contribute to an appreciation of the complex mechanisms that are instrumental in the development of essential hypertension. The racial differences in severity of hypertensive cardiovascular disease in adults coupled with observations now being made in children illustrating a racial influence on factors related to blood pressure levels, help to establish differing mechanisms that are potentially operative in the production of essential hypertension. The potential difference in renal tubular handling of electrolytes is consistent with a different phylogenetic development of racial groups, which are now being exposed to similar environmental conditions of salt consumption that has a greater deleterious effect in blacks. ACKNOWLEDGMENT We thank Imogene W. Talley for her outstanding work as a community coordinator, the entire Bogalusa Heart Study staff for their measurement assistance, and the Bogalusa children and their parents without whom this study would not have been possible.

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RACIAL DIFFERENCES IN CHILD HYPERTENSION

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