Origins of the "Black/White" Difference in Blood Pressure
http://www.100md.com
循环学杂志 2005年第4期
the Tulane Center for Cardiovascular Health (J.K.C., F.M., L.L., L.K., S.R.S., G.S.B.) and the Departments of Epidemiology (J.K.C., F.M., R.S., S.R.S., G.S.B.) and Biostatistics (L.S.W.)
Tulane University Medical Center School of Public Health, New Orleans, La
the Clinical Epidemiology Group (J.K.C.), University of Manchester Medical School, Manchester, England.
Abstract
Background— The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence.
Methods and Results— Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years.
Conclusions— If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.
Key Words: blood pressure ; birth weight ; ethnic groups ; pediatrics
Introduction
The idea that the development of blood vessel structure and function could be influenced by early somatic growth emerged from observations of the tracking of blood pressure (BP) during childhood.1–6 Previous findings from cross-sectional surveys of the Bogalusa Heart study showed that height and ponderosity (wt/ht3) of African-American ("black") and European-American ("white") children were both strong correlates of BP at ages 5 to 14 years.7–9 Longitudinal data also indicated not only that initial BP measured from 4 years and older was the most powerful determinant of later BP levels (one definition of "tracking") in blacks and whites but also that later height and weight (as wt/ht3) were further independent determinants.1–3,6 Data from the Muscatine and other longitudinal studies of BP in childhood showed similar effects, but in whites only.5,10 Initial (birth or first year) height and weight were not included in those earlier Bogalusa analyses. The rise in BP in a younger Bogalusa age group of 2.5 to 5 years old was much less than at older ages but depended on its interaction with other standard cardiovascular risk factors11–13 and was also clearly correlated with height,13 with little effect of race/ethnicity.
Birth weight for gestational age, an indicator of fetal growth, has been an independent predictor of later adult high BP in many studies,14 but the strength of the relation has recently been questioned.15 Initial studies in Bogalusa showed relatively weak effects of birth weight on BP except in black males, but follow-up then extended only to ages 7 to 11 years16 before the ethnic difference of higher BP in blacks emerged. Postnatal or first-year growth, perhaps dependent on intrauterine growth performance, may also be important.17,18 Marked changes in postinfant growth, as "catch-up" or faltering growth, across centiles of growth trajectories have been associated with later adult coronary heart disease,19,20 but much less is known of their impact on BP in later life.
In the present study, we tested the hypothesis that the later ethnic/racial differences in BP between black and white adolescents could be accounted for by differences in intrauterine growth, as assessed by birth weight, and in early rather than later childhood growth. We also tested whether any effect of intrauterine growth on later BP could be confounded by very early effects of childhood BP per se.21 Reliable measures of early BP have rarely been available in previous studies. To examine these issues and to compare their relative impact on blacks versus whites, we analyzed the effects of growth from birth to 4 years and of early BP levels on later BP at age 15 to 17 years, uniquely possible to date in a longitudinal component of the Bogalusa Heart Study.
Methods
Participants
In 1973, a large, community-based study of the natural history of cardiovascular disease was started among school children and adolescents in Bogalusa, La, a semirural, biethnic community where paper production was and is the major industry and employer. A detailed description of the demographic characteristics of the biethnic community, as well as the overall design of this large study, has been published elsewhere.1–3,6–9 Since the beginning of the study, participants have been screened several times, with participation rates ranging between 80% and 93%. Throughout follow-up, ethnicity was that assigned by the mother.
Two cohorts from the Bogalusa Heart Study were included in this study. The first cohort was born in 1973 to 1974, and measurements were taken at birth and then at ages 6 months and 1, 2, 3, and 4 years (n=102). The second cohort was born between 1976 and 1980. They were examined at age 4 to 5 years, and their birth weights were obtained from records in the Office of Vital Statistics in New Orleans (n=83), where these data are derived from reports of direct measures, though not of the same quality as in the birth cohort. Participants from both cohorts combined (total=185) took part in subsequent cross-sectional surveys between 1992 and 1994 and between 1995 and 1996 at ages 15 to 17 years. Birth weights in the second group were slightly greater in all ethnic/sex groups than in the birth cohort; their next measures were recorded toward the end of their fourth and early in their fifth year, but their adolescent data were closely comparable (data available on request).
Procedures
All observations were made and collected by trained personnel following the same protocol described previously.1 Height was measured manually to the nearest 1 mm, and weight, to the nearest 0.01 kg with a balance-beam scale, both as the mean of 2 measurements. BP was measured with a cuff size suitable to the arm circumference (average of 6 measurements, 3 in each arm of 2 consecutive sessions on calibrated electronic and mercury sphygmomanometers). Systolic BP was recorded at the first Korotkoff phase. Fourth- and fifth-phase measurements of diastolic BP were used in analyses. Body mass index (BMI) is weight (kg) divided by the square of height (m2). Differences between birth weight and weight at age 4 (WT04), between height at 6 months (because it was not measured at birth) and 4 to 5 years, between weight and height at 4 years, and between adolescent weight (WT415) and height were used as indices of early and later childhood growth.
Statistical Analysis
Data are presented as means and 95% confidence intervals. For multivariate analyses with linear regression, separate models were constructed for the 2 outcome variables of adolescent systolic and diastolic BP. Independent variables were birth weight, sex, ethnic group, systolic or diastolic BP at age 4 to 5 years, adolescent height, and BMI. In addition, because the cohorts were pooled, early and later childhood growth was defined as the change in weight from birth to 4 to 5 years (WT04) and from 4 to 5 to 15 years (WT415), respectively. These variables were included in the models simultaneously because each was hypothesized to have potentially independent effects on later BP. Interactions between birth weight and ethnic group (birth weightxethnic group) or birth weight and later growth and ethnicity were tested. Standardized coefficients allow direct numerical comparison of the strength of effect between variables. For all analyses, 2-sided tests were performed with a 5% significance level. All analyses were performed with either SPSS version 11 for Windows or SAS.
Results
The cohort was approximately evenly balanced by ethnic and sex groups (n=47 to 50 each except for black girls [n=41]; Table 1). The birth weights of black infants were a mean of 443 and 282 g lighter than those in white infants, highly significantly so in both boys and girls, respectively. In the subgroup with an ethnic and sex distribution similar to that of the total sample and who had annual measures of height and weight recorded (n=102), BP tended to track, so that after the children were stratified into quartiles of BP at the age of 2 years, on average, BPs at 3, 4, and 15 to 17 years were still in those original quartiles (Figure).
Persistence of systolic blood pressure quartiles at age 2 years by subsequent ages 3, 4, and 15 to 17 years.
By age 4 to 5 years, weights and heights were similar in black and white boys, but black girls were marginally heavier and slightly taller than white girls. Thus, the black children showed slightly but not significantly more catch-up growth. At age 4 to 5 years, BPs were little different in boys, and systolic BPs were still marginally lower in black girls, a previous finding at this age in Bogalusa.13
By the age of 15 years, BMIs were almost identical between blacks and whites, but BMI disguised a significant mean difference of 4 cm in height and of 3 kg in weight between white and black boys (the latter still smaller), but no differences in girls (Table 2). Comparison of the change in weight between birth and 4 to 5 years showed that, on average, black children had increased an extra 0.3 to 0.6 kg than whites, but then between 4 to 5 and 15 years, white boys increased an extra 4 kg, on average, with respect to black boys. Despite this, BPs were 3.4/2 mm Hg higher in black than in white boys, but there was little overt difference in BPs among girls; however, the overall difference between blacks and whites in BP remained significant after adjustment for age and other variables (P<0.05).
Regression Models
Discussion
These data suggest that, at least in the setting of the Bogalusa study, ethnic differences in BP that emerge so powerfully between African-ancestry and European-ancestry Americans during adolescence can be accounted for by differences in intrauterine growth, as indicated by birth weight, followed by slightly lesser effects of early weight gain and growth in height and then of current stature. An independent effect of early BP (at age 4 to 5 years) was also present but weaker, and it did not confound the impact of the other factors. The timing of the effects of further somatic growth on vascular development may be important; it was only evident between birth and 4 to 5 years here, with no significant additional effect of growth from 4 or 5 to 15 years. However, such an effect is implied by the additional significant impact of BMI at age 15 to 17 years in the final model.
The multiple-regression results demonstrate the nature and considerable impact of the effects (see standardized coefficients, Table 3) from all of these measures when considered prospectively. Sex was no longer included (as noted elsewhere in a meta-analysis22). The effect of postnatal growth on BP therefore seems to depend on the age at which the infant starts on his/her growth curve, which is what birth weight (or early length) signifies. Only a proportion of the cohort had BPs measured as early as 1 year; when this variable was included in that smaller dataset (n=98) instead of the BPs at year 4, the effect was similar (data not shown). However, BPs taken at this early age may reflect an infant’s response to the procedure as much as BP itself and therefore might not be reliable.
A link between fetal growth conditions, marked by birth weight at term, and later (adult) BP was first postulated in 199321 and was found in many but not all subsequent studies.14 Controversy about the link recently emerged from a more recent meta-analysis, which suggested that there had been considerable publication bias of positive over negative results, overemphasis on studies from the group who originally reported the link, and most important, marked diminution of the effect size in larger compared with smaller studies.15 However, although some of these criticisms were valid, subsequent correspondence including our own pointed out that weighting of the meta-analysis by the largest studies was flawed, not the least because of the 30% imprecision in birth weight self-recall in the 2 largest reports,23,24 and that in 2 of those, there was a clear relation between birth weight and "hypertension" (relative risk of 1.26 in men and of 1.4 in women); in addition, most men in the upper BP quintiles were receiving BP treatment, so that absolute BP values were underestimated. In another very large cohort of Swedish conscripts with a positive link but a small coefficient, the quality of BP measurement without method standardization may not have been high,25 a characteristic relevant to most of the very large studies, which may have led to dilution of any BP–birth weight link.
Another key issue in the controversy about the role of intrauterine growth in determining later vascular development has been the lack of adequate longitudinal data on intervening postnatal and early childhood growth.17 The data provided here, though still of a small sample, provide carefully standardized intermediary measures of such growth as recorded by using carefully standardized, prospective measures. The cohort studied was reduced in size from its original potential, because those without intervening measures, either from birth to any of the annual reviews up to age 4 to 5 years or then up to 15 to 17 years, were not included to maintain the integrity of the intervening data points. Those retained here had characteristics of birth weight and later BP, height, and weight by ethnic and sex groups similar to those of the entire original cohort (data not shown).
Few studies have included genuinely longitudinal data on growth and repeated BP measures under the same conditions. In the earlier Bogalusa report, in much larger numbers, the maximum age of children included was 11 years, ie, before the ethnic difference in BP emerged.17 However, much larger, fully longitudinal data sets are needed, with relevant standardized measures included at several time points. We expect to be able to do this in subsequent studies with further follow-up of original Bogalusa children who are now well into adulthood. Other independent cohorts will be needed also; if the effect is real and repeatable, the result that black-white differences in BP begin in early life will be a major clue to understanding its etiology. Of note for the current report, when a regression model was run according to sex (thus reducing its power because of a decrease in sample size), ethnicity no longer had a significant effect on BP in girls because black/white BP differences were so small, now a well-known finding, based on a meta-analysis that reviewed studies of BP including this age range.26 It was perhaps unusual that the BMIs of black girls were not greater than those of white girls at 15 to 17 years. Compared with national (US) data and other Bogalusa cohorts, as recently reviewed,26 BMI in white girls in this analysis was found to be 1 kg/m2 higher than that 8-study average, but the black girls’ BMIs were as expected from the data of Rosner et al. These slightly higher BMIs in white girls may therefore have reduced any black/white difference in BP that may be emerging at this age.
Similar effects of birth weight have been found for BP differences within samples of African-ancestry children, eg, in the Caribbean,27 and so may be highly relevant to ethnic differences in BP elsewhere, such as between migrant African Caribbeans and Europeans.28 Very few datasets have been available in which the ethnic black/white BP difference and the factors that contribute to it could be examined over time. To our knowledge, based on an electronic literature search, only one other study has examined the issue of birth weight in black Americans in relation to later BP with the use of original data,29 although the hypothesis that such a link might account for excess vascular disease was suggested earlier.30 No study seems to have tested the hypothesis herein that the ethnic black/white BP differences consistently reported in the United States might be related to intrauterine growth differences as reflected by birth dimensions, except our earlier report from Bogalusa in much younger children.16 In the report of Falkner et al,29 137 black American children in the Philadelphia Perinatal Study were followed up to age 28 years, with several intervening measures of growth and BP from early life. No relation was found between birth weight and BP at age 28 years in either men or women or in subgroups of lower birth weight or ponderal index, as an indicator of thinness at birth. Later BP was related only to growth (in height) in males but surprisingly not in females, in whom the correlation was with weight. There is no clear explanation for the divergence in results between the current report and that of Falkner et al. However, a key factor may be that the Bogalusa Study has always been a prospective cohort in which measurement methods and their validation have hardly changed since inception, whereas aspects of the similarly small Philadelphia Study were retrospective. In our recent analysis at older ages, without intervening early growth data, birth weight was again related to BP.31 Clearly, further follow-up to later adulthood, already under way for the Bogalusa Study, and replication of results in other studies are important requirements to verify the current findings. Another issue to consider is that because ethnicity and birth weight are so closely interrelated, attributing causality to the effects of birth weight, or what it signifies in fetal growth, may be only a "mathematical" effect in the statistical models herein, rather than a true biological effect. A cohort study design cannot disentangle this issue, but because ethnicity is unchangeable, concentrating public health efforts on improving fetal growth should have major benefits and experimentally would answer this question directly.
Adult burdens of cardiovascular disease across the world will continue as the proportion of older people in most populations increases; recent estimates from the Global Burden of Disease project placed high BP second in the list of main contributing factors in the 1990s.32 That figure may be an underestimate because data were missing from sub-Saharan Africa, whose populations and those of African descent elsewhere experience an excess prevalence of hypertension.33 African-American babies born at term continue to have lower birth weights than do neonates with predominantly European ancestry,34 as do those elsewhere.35 Important public health benefits could arise if the rate of rise of BP with aging could be slowed, perhaps particularly if small improvements made early in life lead to greater gains later. The data presented here, especially if they can be reproduced in larger or nationally representative datasets, suggest that much of the excess prevalence in (high) BP, so common in black Americans, could be reduced by appropriate early growth but restrained weight gain by adolescence.
References
Voors AW, Webber LS, Berenson GS. Time course studies of blood pressure in children: the Bogalusa Heart Study. Am J Epidemiol. 1979; 109: 320–334.
Voors AW, Webber LS, Berenson GS. Time course study of blood pressure in children over a 3-year period: Bogalusa Heart Study. Hypertension. 1980; 2: 102–108.
Shear CL, Burke G, Freedman DS, Berenson GS. Value of childhood blood pressure measurements and family history in predicting future blood pressure status: results from 8 years of follow-up in the Bogalusa Heart Study. Pediatrics. 1986; 77: 862–869.
Lauer RM, Clarke WR. A longitudinal view of blood pressure during childhood: the Muscatine Study. Stat Med. 1988; 7: 47–57.
Gillman MW, Rosner B, Evans DA, Keough ME, Smith LA, Taylor JO, Hennekens CH. Use of multiple visits to increase blood pressure tracking correlations in childhood. Pediatrics. 1991; 87: 708–711.
Bao W, Threefoot SA, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: the Bogalusa Heart Study. Am J Hypertens. 1995; 8: 657–656.
Voors A, Foster T, Frerichs R, Webber L, Berenson G. Studies of blood pressures in children, ages 5–14 years, in a total biracial community: the Bogalusa Heart Study. Circulation. 1976; 54: 319–327.
Voors A, Webber L,. Frerichs R, Berenson G. Body height and body mass as determinants of basal blood pressure in children: the Bogalusa Heart Study. Am J Epidemiol. 1977; 106: 101–108.
Voors A, Harsha D, Webber L, Berenson G. Relation of blood pressure to stature in healthy young adults. Am J Epidemiol. 1982; 115: 833–840.
Lauer RM, Clarke R. Childhood risk factors for high adult blood pressure: the Muscatine study. Pediatrics. 1989; 79: 1–25.
Foster TA, Voors AW, Webber LS, Frerichs RR. Berenson GS. Anthropometric and maturation measurements of children ages 5–14 years in a biracial community: the Bogalusa Heart Study. Am J Clin Nutr. 1977; 30: 582–591.
Berenson GS, Foster TA, Frank GC, Frerichs RR, Srinivasan SR, Voors AW, Webber LS. Cardiovascular disease risk factor variables at the pre-school age: the Bogalusa Heart Study. Circulation. 1978; 57: 603–612.
Voors AW, Webber LS, Berenson GS. Blood pressure of children, ages 2-5 years, in a total community: the Bogalusa Heart Study. Am J Epidemiol. 1978; 107: 403–411.
Huxley RR, Shiell AW, Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: systematic review of the literature. J Hypertens. 2000; 18: 815–831.
Huxley R, Neil A, Collins R. Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure; [see comment]. Lancet. 2002; 360: 659–665.
Donker GA, Labarthe DR, Harrist RB, Selwyn BJ, Wattigney W, Berenson GS. Low birth weight and blood pressure at age 7–11 years in a biracial sample. Am J Epidemiol. 1997; 145: 387–397.
Lucas A, Fewtrell MS, Cole TJ. Fetal origins of adult diseases: the hypothesis revisited. BMJ. 1999; 319: 245–249.
Singhal A, Wells J, Cole TJ, Fewtrell M, Lucas A. Programming of lean body mass: a link between birth weight, obesity, and cardiovascular disease; Am J Clin Nutr. 2003; 77: 26–30.
Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJP. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ. 1999; 318: 427–431.
Barker DJP. Mothers, Babies and Health in Later Life, 2nd ed. Edinburgh, Scotland: Churchill Livingstone; 1998.
Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJ, Cruddas AM, Fall CH. Initiation of hypertension in utero and its amplification throughout life. BMJ. 1993; 306: 24–27.
Lawlor DA, Ebrahim S, Davey Smith G. Is there a sex difference in the association between birth weight and systolic blood pressure in later life; Findings from meta-regression analysis. Am J Epidemiol. 2002; 156: 1100–1104.
Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, Manson JE, Speizer FE, Stampfer MJ. Birth weight and adult hypertension and obesity in women. Circulation. 1996; 94: 1310–1315.
Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation. 1996; 94: 3246–3250.
Nilsson PM, Ostergren PO, Nyberg P, Soderstrom M, Allebeck P. Low birth weight is associated with elevated systolic blood pressure in adolescence: a prospective study of a birth cohort of 149378 Swedish boys. J Hypertens. 1997; 15 (pt 2): 1627–1631.
Rosner B, Prineas R, Daniels SR, Loggie J. Blood pressure differences between blacks and whites in relation to body size among US children and adolescents. Am J Epidemiol. 2000; 151: 1007–1019.
Forrester TE, Wilks R, Bennett FI, Simeon D, Osmond C, Allen M, Chung AP, Scott P. Fetal growth and cardiovascular risk factors in Jamaican schoolchildren. BMJ. 1996; 312: 156–160.
Cruickshank JK, Mbanya JC, Wilks R, Balkau B, McFarlane-Anderson N, Forrester T. Sick genes, sick individuals or sick populations with chronic disease; The emergence of diabetes and high blood pressure in African-origin populations. Int J Epidemiol. 2001; 30: 111–117.
Falkner B, Hulman S, Kushner H. Birth weight versus childhood growth as determinants of adult blood pressure. Hypertension. 1998; 31: 145–150.
Lopes AA, Port FK. The low birth weight hypothesis as a plausible explanation for the black/white differences in hypertension, non–insulin-dependent diabetes, and end-stage renal disease. Am J Kidney Dis. 1995; 25: 350–356.
Mzayek F, Sherwin R, Fonseca V, Valdez R, Srinivasan S, Cruickshank JK, Berenson GS. Differential associations of birth weight with multiple cardiovascular risk variables in blacks and whites: the Bogalusa Heart Study. Ann Epidemiol. 2004; 14: 258–264.
Ezzati M, Hoorn SV, Rodgers A, Lopez AD, Mathers CD, Murray CJ; Comparative Risk Assessment Collaborating Group. Estimates of global and regional potential health gains from reducing multiple major risk factors [see comment]. Lancet. 2003; 362: 271–280.
Cooper RS, Rotimi CN, Kaufman JS, Muna WF, Mensah GA. Hypertension treatment and control in sub-Saharan Africa: the epidemiological basis for policy. BMJ. 1998; 316: 614–617.
Alexander GR, Kogan M, Bader D, Carlo W, Allen M, Mor J. US birth weight/gestational age-specific neonatal mortality: 1995–1997 rates for whites, Hispanics, and blacks. Pediatrics. 2003; 111; e61–e66.
Harding S, Rosato MG, Cruickshank JK. Lack of change in birthweights of infants by generational status among Indian, Pakistani, Bangladeshi, Black Caribbean, and Black African mothers in a British cohort study. Int J Epidemiol. 2004; 33: 1279–1285.(J.K. Cruickshank, MD; F. )
Tulane University Medical Center School of Public Health, New Orleans, La
the Clinical Epidemiology Group (J.K.C.), University of Manchester Medical School, Manchester, England.
Abstract
Background— The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence.
Methods and Results— Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years.
Conclusions— If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.
Key Words: blood pressure ; birth weight ; ethnic groups ; pediatrics
Introduction
The idea that the development of blood vessel structure and function could be influenced by early somatic growth emerged from observations of the tracking of blood pressure (BP) during childhood.1–6 Previous findings from cross-sectional surveys of the Bogalusa Heart study showed that height and ponderosity (wt/ht3) of African-American ("black") and European-American ("white") children were both strong correlates of BP at ages 5 to 14 years.7–9 Longitudinal data also indicated not only that initial BP measured from 4 years and older was the most powerful determinant of later BP levels (one definition of "tracking") in blacks and whites but also that later height and weight (as wt/ht3) were further independent determinants.1–3,6 Data from the Muscatine and other longitudinal studies of BP in childhood showed similar effects, but in whites only.5,10 Initial (birth or first year) height and weight were not included in those earlier Bogalusa analyses. The rise in BP in a younger Bogalusa age group of 2.5 to 5 years old was much less than at older ages but depended on its interaction with other standard cardiovascular risk factors11–13 and was also clearly correlated with height,13 with little effect of race/ethnicity.
Birth weight for gestational age, an indicator of fetal growth, has been an independent predictor of later adult high BP in many studies,14 but the strength of the relation has recently been questioned.15 Initial studies in Bogalusa showed relatively weak effects of birth weight on BP except in black males, but follow-up then extended only to ages 7 to 11 years16 before the ethnic difference of higher BP in blacks emerged. Postnatal or first-year growth, perhaps dependent on intrauterine growth performance, may also be important.17,18 Marked changes in postinfant growth, as "catch-up" or faltering growth, across centiles of growth trajectories have been associated with later adult coronary heart disease,19,20 but much less is known of their impact on BP in later life.
In the present study, we tested the hypothesis that the later ethnic/racial differences in BP between black and white adolescents could be accounted for by differences in intrauterine growth, as assessed by birth weight, and in early rather than later childhood growth. We also tested whether any effect of intrauterine growth on later BP could be confounded by very early effects of childhood BP per se.21 Reliable measures of early BP have rarely been available in previous studies. To examine these issues and to compare their relative impact on blacks versus whites, we analyzed the effects of growth from birth to 4 years and of early BP levels on later BP at age 15 to 17 years, uniquely possible to date in a longitudinal component of the Bogalusa Heart Study.
Methods
Participants
In 1973, a large, community-based study of the natural history of cardiovascular disease was started among school children and adolescents in Bogalusa, La, a semirural, biethnic community where paper production was and is the major industry and employer. A detailed description of the demographic characteristics of the biethnic community, as well as the overall design of this large study, has been published elsewhere.1–3,6–9 Since the beginning of the study, participants have been screened several times, with participation rates ranging between 80% and 93%. Throughout follow-up, ethnicity was that assigned by the mother.
Two cohorts from the Bogalusa Heart Study were included in this study. The first cohort was born in 1973 to 1974, and measurements were taken at birth and then at ages 6 months and 1, 2, 3, and 4 years (n=102). The second cohort was born between 1976 and 1980. They were examined at age 4 to 5 years, and their birth weights were obtained from records in the Office of Vital Statistics in New Orleans (n=83), where these data are derived from reports of direct measures, though not of the same quality as in the birth cohort. Participants from both cohorts combined (total=185) took part in subsequent cross-sectional surveys between 1992 and 1994 and between 1995 and 1996 at ages 15 to 17 years. Birth weights in the second group were slightly greater in all ethnic/sex groups than in the birth cohort; their next measures were recorded toward the end of their fourth and early in their fifth year, but their adolescent data were closely comparable (data available on request).
Procedures
All observations were made and collected by trained personnel following the same protocol described previously.1 Height was measured manually to the nearest 1 mm, and weight, to the nearest 0.01 kg with a balance-beam scale, both as the mean of 2 measurements. BP was measured with a cuff size suitable to the arm circumference (average of 6 measurements, 3 in each arm of 2 consecutive sessions on calibrated electronic and mercury sphygmomanometers). Systolic BP was recorded at the first Korotkoff phase. Fourth- and fifth-phase measurements of diastolic BP were used in analyses. Body mass index (BMI) is weight (kg) divided by the square of height (m2). Differences between birth weight and weight at age 4 (WT04), between height at 6 months (because it was not measured at birth) and 4 to 5 years, between weight and height at 4 years, and between adolescent weight (WT415) and height were used as indices of early and later childhood growth.
Statistical Analysis
Data are presented as means and 95% confidence intervals. For multivariate analyses with linear regression, separate models were constructed for the 2 outcome variables of adolescent systolic and diastolic BP. Independent variables were birth weight, sex, ethnic group, systolic or diastolic BP at age 4 to 5 years, adolescent height, and BMI. In addition, because the cohorts were pooled, early and later childhood growth was defined as the change in weight from birth to 4 to 5 years (WT04) and from 4 to 5 to 15 years (WT415), respectively. These variables were included in the models simultaneously because each was hypothesized to have potentially independent effects on later BP. Interactions between birth weight and ethnic group (birth weightxethnic group) or birth weight and later growth and ethnicity were tested. Standardized coefficients allow direct numerical comparison of the strength of effect between variables. For all analyses, 2-sided tests were performed with a 5% significance level. All analyses were performed with either SPSS version 11 for Windows or SAS.
Results
The cohort was approximately evenly balanced by ethnic and sex groups (n=47 to 50 each except for black girls [n=41]; Table 1). The birth weights of black infants were a mean of 443 and 282 g lighter than those in white infants, highly significantly so in both boys and girls, respectively. In the subgroup with an ethnic and sex distribution similar to that of the total sample and who had annual measures of height and weight recorded (n=102), BP tended to track, so that after the children were stratified into quartiles of BP at the age of 2 years, on average, BPs at 3, 4, and 15 to 17 years were still in those original quartiles (Figure).
Persistence of systolic blood pressure quartiles at age 2 years by subsequent ages 3, 4, and 15 to 17 years.
By age 4 to 5 years, weights and heights were similar in black and white boys, but black girls were marginally heavier and slightly taller than white girls. Thus, the black children showed slightly but not significantly more catch-up growth. At age 4 to 5 years, BPs were little different in boys, and systolic BPs were still marginally lower in black girls, a previous finding at this age in Bogalusa.13
By the age of 15 years, BMIs were almost identical between blacks and whites, but BMI disguised a significant mean difference of 4 cm in height and of 3 kg in weight between white and black boys (the latter still smaller), but no differences in girls (Table 2). Comparison of the change in weight between birth and 4 to 5 years showed that, on average, black children had increased an extra 0.3 to 0.6 kg than whites, but then between 4 to 5 and 15 years, white boys increased an extra 4 kg, on average, with respect to black boys. Despite this, BPs were 3.4/2 mm Hg higher in black than in white boys, but there was little overt difference in BPs among girls; however, the overall difference between blacks and whites in BP remained significant after adjustment for age and other variables (P<0.05).
Regression Models
Discussion
These data suggest that, at least in the setting of the Bogalusa study, ethnic differences in BP that emerge so powerfully between African-ancestry and European-ancestry Americans during adolescence can be accounted for by differences in intrauterine growth, as indicated by birth weight, followed by slightly lesser effects of early weight gain and growth in height and then of current stature. An independent effect of early BP (at age 4 to 5 years) was also present but weaker, and it did not confound the impact of the other factors. The timing of the effects of further somatic growth on vascular development may be important; it was only evident between birth and 4 to 5 years here, with no significant additional effect of growth from 4 or 5 to 15 years. However, such an effect is implied by the additional significant impact of BMI at age 15 to 17 years in the final model.
The multiple-regression results demonstrate the nature and considerable impact of the effects (see standardized coefficients, Table 3) from all of these measures when considered prospectively. Sex was no longer included (as noted elsewhere in a meta-analysis22). The effect of postnatal growth on BP therefore seems to depend on the age at which the infant starts on his/her growth curve, which is what birth weight (or early length) signifies. Only a proportion of the cohort had BPs measured as early as 1 year; when this variable was included in that smaller dataset (n=98) instead of the BPs at year 4, the effect was similar (data not shown). However, BPs taken at this early age may reflect an infant’s response to the procedure as much as BP itself and therefore might not be reliable.
A link between fetal growth conditions, marked by birth weight at term, and later (adult) BP was first postulated in 199321 and was found in many but not all subsequent studies.14 Controversy about the link recently emerged from a more recent meta-analysis, which suggested that there had been considerable publication bias of positive over negative results, overemphasis on studies from the group who originally reported the link, and most important, marked diminution of the effect size in larger compared with smaller studies.15 However, although some of these criticisms were valid, subsequent correspondence including our own pointed out that weighting of the meta-analysis by the largest studies was flawed, not the least because of the 30% imprecision in birth weight self-recall in the 2 largest reports,23,24 and that in 2 of those, there was a clear relation between birth weight and "hypertension" (relative risk of 1.26 in men and of 1.4 in women); in addition, most men in the upper BP quintiles were receiving BP treatment, so that absolute BP values were underestimated. In another very large cohort of Swedish conscripts with a positive link but a small coefficient, the quality of BP measurement without method standardization may not have been high,25 a characteristic relevant to most of the very large studies, which may have led to dilution of any BP–birth weight link.
Another key issue in the controversy about the role of intrauterine growth in determining later vascular development has been the lack of adequate longitudinal data on intervening postnatal and early childhood growth.17 The data provided here, though still of a small sample, provide carefully standardized intermediary measures of such growth as recorded by using carefully standardized, prospective measures. The cohort studied was reduced in size from its original potential, because those without intervening measures, either from birth to any of the annual reviews up to age 4 to 5 years or then up to 15 to 17 years, were not included to maintain the integrity of the intervening data points. Those retained here had characteristics of birth weight and later BP, height, and weight by ethnic and sex groups similar to those of the entire original cohort (data not shown).
Few studies have included genuinely longitudinal data on growth and repeated BP measures under the same conditions. In the earlier Bogalusa report, in much larger numbers, the maximum age of children included was 11 years, ie, before the ethnic difference in BP emerged.17 However, much larger, fully longitudinal data sets are needed, with relevant standardized measures included at several time points. We expect to be able to do this in subsequent studies with further follow-up of original Bogalusa children who are now well into adulthood. Other independent cohorts will be needed also; if the effect is real and repeatable, the result that black-white differences in BP begin in early life will be a major clue to understanding its etiology. Of note for the current report, when a regression model was run according to sex (thus reducing its power because of a decrease in sample size), ethnicity no longer had a significant effect on BP in girls because black/white BP differences were so small, now a well-known finding, based on a meta-analysis that reviewed studies of BP including this age range.26 It was perhaps unusual that the BMIs of black girls were not greater than those of white girls at 15 to 17 years. Compared with national (US) data and other Bogalusa cohorts, as recently reviewed,26 BMI in white girls in this analysis was found to be 1 kg/m2 higher than that 8-study average, but the black girls’ BMIs were as expected from the data of Rosner et al. These slightly higher BMIs in white girls may therefore have reduced any black/white difference in BP that may be emerging at this age.
Similar effects of birth weight have been found for BP differences within samples of African-ancestry children, eg, in the Caribbean,27 and so may be highly relevant to ethnic differences in BP elsewhere, such as between migrant African Caribbeans and Europeans.28 Very few datasets have been available in which the ethnic black/white BP difference and the factors that contribute to it could be examined over time. To our knowledge, based on an electronic literature search, only one other study has examined the issue of birth weight in black Americans in relation to later BP with the use of original data,29 although the hypothesis that such a link might account for excess vascular disease was suggested earlier.30 No study seems to have tested the hypothesis herein that the ethnic black/white BP differences consistently reported in the United States might be related to intrauterine growth differences as reflected by birth dimensions, except our earlier report from Bogalusa in much younger children.16 In the report of Falkner et al,29 137 black American children in the Philadelphia Perinatal Study were followed up to age 28 years, with several intervening measures of growth and BP from early life. No relation was found between birth weight and BP at age 28 years in either men or women or in subgroups of lower birth weight or ponderal index, as an indicator of thinness at birth. Later BP was related only to growth (in height) in males but surprisingly not in females, in whom the correlation was with weight. There is no clear explanation for the divergence in results between the current report and that of Falkner et al. However, a key factor may be that the Bogalusa Study has always been a prospective cohort in which measurement methods and their validation have hardly changed since inception, whereas aspects of the similarly small Philadelphia Study were retrospective. In our recent analysis at older ages, without intervening early growth data, birth weight was again related to BP.31 Clearly, further follow-up to later adulthood, already under way for the Bogalusa Study, and replication of results in other studies are important requirements to verify the current findings. Another issue to consider is that because ethnicity and birth weight are so closely interrelated, attributing causality to the effects of birth weight, or what it signifies in fetal growth, may be only a "mathematical" effect in the statistical models herein, rather than a true biological effect. A cohort study design cannot disentangle this issue, but because ethnicity is unchangeable, concentrating public health efforts on improving fetal growth should have major benefits and experimentally would answer this question directly.
Adult burdens of cardiovascular disease across the world will continue as the proportion of older people in most populations increases; recent estimates from the Global Burden of Disease project placed high BP second in the list of main contributing factors in the 1990s.32 That figure may be an underestimate because data were missing from sub-Saharan Africa, whose populations and those of African descent elsewhere experience an excess prevalence of hypertension.33 African-American babies born at term continue to have lower birth weights than do neonates with predominantly European ancestry,34 as do those elsewhere.35 Important public health benefits could arise if the rate of rise of BP with aging could be slowed, perhaps particularly if small improvements made early in life lead to greater gains later. The data presented here, especially if they can be reproduced in larger or nationally representative datasets, suggest that much of the excess prevalence in (high) BP, so common in black Americans, could be reduced by appropriate early growth but restrained weight gain by adolescence.
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