Racial Aspects of Blood Pressure in Children and Adolescents

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CHILDHOOD HYPERTENSION

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RACIAL ASPECTS OF BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS Bruce S. Alpert, MD, and Mary E. Fox, MS

RACIAL DIFFERENCES IN CASUAL BLOOD PRESSURE: A META-ANALYSIS

The incidence, prevalence, and severity of essential hypertension is higher in minority adult populations, especially black Americans. Studies have not uniformly shown that, for example, black children and adolescents have higher blood pressure values than whites of the same age. Fewer data are available for Hispanic and Oriental populations of children and adolescents. The goals of this article are to review data available comparing minority and white populations. * Differences among populations were compared by a meta-analysis. In addition, a small section discussing studies addressing racial differences in related topics is included to demonstrate the existing fields of research that may not be familiar to the general pediatrician. Within this second section several hypotheses are raised to explain the greater prevalence of hypertension in the black community. Statistical Methodology

To determine whether there are differences among races-white, black, Hispanic, Oriental-for published values of systolic or diastolic *References 3, 4, 6, 10, IS, 16, 19, 20, 22-24, 29-32, 34-37, 39, 40, 42-44, 48-52, 5661.

From the Division of Pediatric Cardiology, University of Tennessee, Memphis, School of Medicine (BSA, MEF); and University of Tennessee Prevention Institute (BSA); Memphis, Tennessee

PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 40 • NUMBER 1 • FEBRUARY 1993

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ALPERT & FOX

blood pressure, by age group and sex, we performed several analyses. First, we separated studies into those reporting data from birth to 12 years of age (Group 1); 13 to 18 years (Group 2); and 19 to 25 years (Group 3). Then we combined all data within each of the three age groups. We included all manuscripts in which at least two racial population groups were included. From the individual papers we calculated a weighted mean for systolic and diastolic blood pressures by race, sex, and age group. We then calculated weighted t values by age group and sex comparing two races at a time, testing the null hypothesis that the value was zero versus the alternative hypothesis that the value was different from zero. We used the reported means, standard deviations, or errors as needed to generate the meta-analysis. In addition, we tabulated the studies that reported racial comparisons but did not have sufficient data presented to enter into the metaanalysis. We were able to identify 35 studies in English that had appropriate data for analysis. In 6 of the studies10, 35, 44, 49, SO, 52 there were no racial differences found. In 4 of these, only black-white differences were sou.ght; whereas in 1 Hispanics were included. There was 1 study that included blacks, whites, and Orientals. The subjects in this study were primarily at or below 12 years of age (Group 1 of the analysis). The results from the other 29 studies are summarized in Table 1. In all of these, there were significant racial differences for either systolic or diastolic blood pressure, either in males or females, when at least two racial subgroups were compared. In the analysis performed, we made no comparisons between males and females. We did not attempt to keep a strict definition of blacks, Orientals, or Hispanics, but rather pooled data into each racial group as identified by each investigator. Results The weighted mean blood pressure values showed the expected increase in systolic blood pressure from childhood to adolescence (Group 1 and Group 2). For the comparisons, we identified 95,068 white subjects, 42,990 blacks, 7846 Hispanics, and 630 Orientals. Mean data for all age groups combined are not useful because a disproportionate number of studies were available for each racial group. Table 2 lists the meta-analysis results by sex and age groups. The meta-analysis revealed several P values less than 0.1. Because it is difficult to assign arbitrary significance to a P of 0.05, 0.01, etc, we chose to tabulate those values that were <0.1 and give the P values. In this way, the reader may judge the clinical significance of the comparative values. Also, because there was no consistency among studies with respect to height, weight, body surface area, and Quetelet Index, adjustments of the data, were it possible, would tend to "improve" these P values. Table 2 demonstrates those race and age groups with P values in the range of interest. Within the group of males, whites did not have any blood pressure values that exceeded any other group's

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RACIAL ASPECfS OF BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS

Table 1. STUDIES IN WHICH RACIAL DIFFERENCES WERE PRESENT A. 0-12 years of age Study # C

SBP

Subjects H B

0

57

54

52

11

1080

513

312

203

16 18

480 2380

446 794

302

313

21 23 28 33

996 121 695 6100

1109 49 443 987

B. 13-18 years of age Study # C

M

DBP F

C>B C>B C>B

C>B

C>B

C>B B>C

B>C

B>C

M

F

2928

C>B

3 5

300 4500

236 4679

1469

6 8 9 11

11,513 4183 4788 538

1874 3315 2050 280

H>B H>C C>B

B>C B>H C>B B>H B>C C>B B>C

149

12 13

177 224

118 2267

1220

14 15 19 21 22 25 30 34

1156 207 996 190 12,483 4433 345 19,552

787 590 947 186 748 1889 58 3024

0

2

Subjects H B

7 20

1371 921

335 1365

B>C B>H O>C O>H

36

83

31

C>B B>C B>H B>O H>C C>B C>B C>H B>C B>C

B>C B>C

B>C B>H B>O

M

F

C>B C>H

C>B C>B C>H

C>B B>C

B>H

C>B

B>C B>C B>C C>B

C>B C>B C>B

C>B C>B

C>B B>C B>H C>H O>H B>C B>C H>C

C>B B>C

B>C C>B B>C C>B

B>C

B>C

SBP 0

B>C B>H O>C O>H C>B

DBP

10,949

60

H>C H>B B>C B>H C>H O>H

B>C B>H B>O

9753

32

H>C H>B B>C

SBP

Subjects B H

2

F

B>C B>H B>O H>C B>C B>C

2

C. 19-24 years of age Study # C

M

DBP

M

F

C>B

B>C B>H B>C

M

F

B>C

Table continued on following page

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Table 1. STUDIES IN WHICH RACIAL DIFFERENCES WERE PRESENT (Continued) D. Studies that span primarily more than one age range Study # Age Subjects SBP

DBP

C

B

H

M

F

M

F

10

3-17

769

658

1383

B>H B>C

5-15 3-17

2220 2508

1304 876

B>H B>C B>C B>C

B>H B>C

31 32

B>H B>C B>C B>C

SBP

Abbreviations: B = black, C = caucasian, F = female, H = Hispanic, M = systolic blood pressure, DBP = diastolic blood pressure.

=

male, 0

=

Oriental,

values. Black males' diastolic values exceeded those of whites and Orientals. The pattern of racial difference seen for females was striking. For the four comparisons considered "significant," blacks' values were higher in each case. For systolic blood pressure, three comparisons met criteria (P
In the extant literature, blood pressure values for healthy white and black children and adolescents are plentiful; more than 140,000 values were available for comparisons. Because of the wide variety of age ranges, however, no trends could be dissected from the data within each age range. The separation at 12 years of age was used because of the changes in body habitus that occur with puberty, the number of studies that separated age groups in this manner, and the recommendation to use KS to assign diastolic blood pressure rather than K4, as recommended by the Second Task Force on Blood Pressure Control in Children: 1987. 59 In six studies primarily comparing white with black populations, no differences for either systolic blood pressure or diastolic blood pressure were found. In the other 29 studies included in the metaanalysis, there were one or more significant (P
Males

Females

Age

Measure

Racial Comparison

P Value

0-12 yr

DBP SBP DBP DBP SBP SBP SBP DBP

B>C H>C B>O O>H B>O B>C B>H B>C

P
0-12 yr 13-18 yr 19-25 yr

RACIAL ASPECTS OF BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS

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higher than those of blacks. This relationship parallels that found in adult literature. The meta-analysis was unable to define a clear pattern, however, with respect to age. If, for example, blood pressure values at birth are equivalent and there is some abnormality of physiology or anatomy that is relentlessly progressive with age, we would have expected that no, or few, comparisons would be significant early in life, and by the age range of 19 to 25, adult patterns would have been achieved. We did not observe this trend. It is clear that additional studies in Hispanics, Orientals, Native Americans, Eskimos, Pacific Islanders, and other minorities are needed to "fill in the blanks" for knowledge concerning normal blood pressure for these populations and to help uncover possible mechanisms for the evolution of essential hypertension in the young adult years. The mechanisms by which adult differences in blood pressure values among races evolve is under study in numerous laboratories. An exhaustive review of this topic is beyond the scope of this article. These investigations seek to define either markers for later-onset hypertension or mechanisms by which this difference may be produced. In the former category, for instance, is cardiovascular reactivity, the change in a physiologic parameter such as heart rate or blood pressure in response to a controlled stressor. Examples in the latter category are studies of renal sodium handling, membrane sodium pump function, or alterations in the renin-angiotensin-aldosterone system. There is not a complete separation of these two categories. If, for instance, repeated blood pressure elevations occur in response to physical and social stressors within a racial group, these repeated and sustained elevations may lead to long-term vascular damage. To the best of our knowledge, the first study that demonstrated a racial difference in cardiovascular reactivity appeared from our laboratory in 1981. 1 At rest, there was no black-white difference in systolic blood pressure between groups of healthy, normotensive 6- to 18-yearold subjects. At maximal dynamic exercise, however, black subjects had consistently higher blood pressure values. We pursued the field of reactivity to demonstrate that the same racial reactivity difference occurred in response to an Atari game, Break Out. 45, 46 Since then, investigators in other laboratories have confirmed and expanded these findings. 14, 38, 41, 47 An excellent review of this topic appeared recently. 2 In this article, Anderson reviewed some of the mechanisms by which cardiovascular reactivity may lead to essential hypertension. These mechanisms included racial differences in renin levels, sodium excretion, and perceptions of the social environment. The topic of sodium metabolism has frequently been studied with respect to black-white blood pressure differences. The term used to encompass these investigations is salt sensitivity, Publications too numerous to count have described that blacks with normotension and hypertension have a greater prevalence of blood pressure response to sodium loading or depletion than do whites. l3 , 55 Whether that effect is produced by a renal mechanism directly or indirectly is still under study. We have found that black normotensive school children have a

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greater sensitivity to sodium manipulation than their white counterparts. For this reason, we would hypothesize that there is an inherited (congenital) difference in the body's metabolism of sodium, because these children are too young to exhibit target organ damage from chronic blood pressure elevations. The erythrocyte membrane has served as a model for the study of transmembrane sodium flux in the vascular endothelium. Studies in our laboratoryS3 and those by Canessa et al/,8 Falkner,13 and others, in humans using skin fibroblast cells,S, 33 also describe black-white differences in sodium membrane transport. Thus, an abnormality of sodium handling present not only in the renal cells but possibly in all cells may lead to lifelong increases in intracellular sodium and altered hemostasis. There is a confirmatory literature I2, 17, 21 from the clinical standpoint of hypertension management that confirms these paths of experimental evidence. It has long been known that blacks who have hypertension usually require a diuretic as part of their successful pharmacologic management.9, 12, 28 The mechanism by which sodium may interact with a blood pressure regulatory endogenous system has been the subject of investigations related to catecholamines and the renin-angiotensin-aldosterone system. Dimsdale et aPI demonstrated a black-white difference in the response to a high salt diet. Blacks showed an increased pressor sensitivity in response to dietary intervention; whites showed a nonsignificant decrease (no change). If blacks consume a diet relatively high in sodium, then the stressors of everyday life may lead to excessive and prolonged blood pressure elevations. The observation in our laboratory by Harshfield et aP that blacks have a reduced nocturnal decline in blood pressure led us to investigate the relationships among the renin-angiotensin-aldosterone system, sodium intake and excretion, and ambulatory blood pressure. 25,27 It would appear that even in normotensive children there are black-white differences in the kidneys' ability to excrete a sodium load associated with alterations in the renin-angiotensin-aldosterone regulatory system that produced sustained higher blood pressures in blacks. Another area that might serve either as a marker or mechanism of increased blood pressure in blacks is left ventricular hemodynamics, as determined by echocardiography. Data from a major ongoing longitudinal study in Bogalusa54 defined black-white differences in the often debated areas of cardiac output and systemic vascular resistance. White males had greater cardiac output and stroke volume, implying a lower systemic vascular resistance. Blacks in this 7- to 22-year-old population had higher systemic vascular resistance, implying that there was a racial difference in hemodynamic mechanisms in this prehypertensive population. The actual properties of blood vessels have been studied from subjects in the Bogalusa study who died between the ages of 6 and 27 years. I8 The black subjects' aortas had a higher prevalence of fatty streaks (37%) than those of white subjects (16%). Even after controlling for antemortem risk factors, blacks had an additional 16% aortic surface involvement than predicted. These data imply an as yet

RACIAL ASPECTS OF BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS

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undefined mechanism of atherosclerosis in blacks. It is well known that hypertension itself is a major risk factor for atherosclerosis, so these black subjects may have demonstrated differing blood pressure patterns if they had undergone ambulatory blood pressure monitoring or cardiovascular reactivity assessment. As mentioned earlier, studies relating to precursors of hypertension or mechanisms of hypertension are plentiful. The reader is referred to an exhaustive review 21 and a recent international congress summary17 for more extensive background material and current work. The mechanisms for the membrane, cellular, and subcellular alterations that lead to the higher prevalence of hypertension in one racial population, blacks, are only partly understood. The work by Canessa7, 8 and Songu-Mize,53 for example, continues to lead to data dissecting to the molecular mechanisms 26 responsible. It is our bias, however, that the "key" finding relates to the relative physiologic excess of sodium in westernized society for a black race that evolved for thousands of generations in a sodium-depleted natural habitat. Sodium is only a marker perturbation in the overall homeostasis controlled by the simultaneous interactions of numerous feedback systems. The direction of future investigations should focus on cellular and subcellular targets. Once the final lock has been opened, we must remember to extend the implications of this knowledge back to pediatricians for aggressive intervention studies. The primary prevention of hypertension, not the effective therapy of a devastating disease, should be our goal as we enter the 21st century. Supported by the Plough Foundation Endowed Chair of Excellence in Pediatrics and NIH R01 HL 35788.

ACKNOWLEDGMENTS The authors would like to thank Greg Harshfield, Grant Somes, Derrick Pulliam, and Judy Adams for their invaluable assistance in the evolution of this article.

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Address reprint requests to Bruce S. Alpert, MD Division of Pediatric Cardiology University of Tennessee, Memphis, School of Medicine Suite 215 777 Washington Avenue Memphis, TN 38105