Black–White Difference in the Impact of Long-Term Blood Pressure From Childhood on Adult Renal Function: The Bogalusa Heart Study

Abstract

BACKGROUND

To examine racial difference in the impact of long-term burden of blood pressure (BP) from childhood on adult renal function between middle-aged blacks and whites.

METHODS

The study cohort consisted of 1,646 whites and 866 blacks aged 20–51 years at follow-up who had BP measured at least 4 times since childhood, with a mean follow-up period of 25.3 years. The area under the curve (AUC) was calculated as a measure of long-term burden of BP from childhood to adulthood. Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine to assess renal function in adulthood.

RESULTS

Black vs. white adults had significantly higher values of eGFR and long-term burden of systolic BP for both males and females. In multivariable linear regression analyses, adjusting for sex, adult age, body mass index, smoking, and alcohol use, adult eGFR was significantly and negatively associated with adult systolic BP (standardized regression coefficient [β] = −0.10, P = 0.005) and diastolic BP (β = −0.11, P = 0.003) in blacks, but not in whites. The total BP AUC values were also significantly and negatively associated with adult eGFR (β = −0.10, P = 0.005 for systolic BP and β = −0.09, P = 0.013 for diastolic BP) in blacks only. Childhood BP was not significantly associated with adult eGFR in blacks and whites.

CONCLUSIONS

These findings suggest that black–white disparities in the influence of elevated BP on the development of renal dysfunction occur in middle adulthood, which underscores the importance of BP control in the black population.

Chronic kidney disease (CKD) affects about 15% of US adults and represents a major public health problem worldwide.¹ CKD is associated with increased risks of all-cause mortality, cardiovascular disease, and progression to kidney failure.^2,3 The 2002 Kidney Disease Outcomes Quality Initiative guidelines define CKD as renal damage (e.g., albuminuria) lasting for >3 months or declining renal function (assessed by glomerular filtration rate, GFR),⁴ and divide CKD into 5 stages based on GFR.⁴ Reduced GFR independently predicts all-cause and cardiovascular mortality and kidney failure.^5–7 Hypertension is an established risk factor for CKD and end-stage renal disease (ESRD).^1,8,9 Longitudinal studies, including ours, have indicated that childhood blood pressure (BP) is significantly associated with microalbumin and GFR as well as risk of ESRD in adulthood,^10–13 indicating a role of elevated BP in early life for the development of renal disease.

In the United States, blacks confer a greater risk of kidney disease compared with whites, particularly in the more severe stages.^14–17 The prevalence of ESRD is 3.7 times greater in blacks than in whites.¹ In addition, blacks outpace other ethnic groups in the United States in terms of prevalence, early onset, and severity of hypertension, which is one of the mechanisms underlying the racial difference in ESRD.¹⁸ Although childhood BP is known to be associated with renal function and risk of ESRD,^10–13 the racial disparity in the early origin of the influence of elevated BP on kidney function remains largely unknown. Utilizing a longitudinal cohort from the Bogalusa Heart Study with multiple BP measurements from childhood to adulthood, the present study aimed to examine the racial difference in the impact of cumulative burden of BP on adult renal function between blacks and whites.

METHODS

Study cohort

The Bogalusa Heart Study, a series of long-term epidemiologic studies in a semirural biracial (65% white and 35% black) community in Bogalusa, Louisiana, was founded in 1973 by Dr Gerald Berenson. This study focuses on the early natural history of cardiovascular disease since childhood.¹⁹ In Bogalusa, Louisiana, 9 cross-sectional surveys of children aged 4–19 years and 11 cross-sectional surveys of adults aged 20–51 years who were previously examined as children were conducted between 1973 and 2010. Linking these repeated cross-sectional examinations conducted every 2–3 years has resulted in serial observations from childhood to adulthood. In the current study, 2,512 subjects (1,646 whites and 866 blacks; 44.6% men) who had data on serum creatinine in adulthood and BP measured 4–15 times (7.1 times on average, at least 2 times in childhood and at least 2 times in adulthood) were included for analysis. The mean follow-up period was 25.3 years.

All subjects in this study gave informed consent at each examination, and consent of a parent/guardian was obtained for those <18 years of age. Study protocols were approved by the Institutional Review Board of the Tulane University Health Sciences Center.

Examinations

Standardized protocols were used by trained examiners across all surveys since 1973. Body mass index (BMI, weight in kilograms divided by height in meters squared) was used as a measure of adiposity. BP levels were measured in 8:00–10:00 am on the right arm of subjects in a relaxed, sitting position by 2 trained observers (3 replicates each). Systolic BP (SBP) and diastolic BP (DBP) were recorded using a mercury sphygmomanometer. The fourth Korotkoff phase was used for DBP for children and adults because it is more reliably measured in childhood and more predictive of adult hypertension.²⁰ The mean values of the 6 readings were used for analysis. Hypertension in adults was defined as SBP ≥140 mm Hg and/or DBP ≥90 mm Hg and/or taking antihypertensive medications. For longitudinal analyses of BP, an SBP/DBP value of 140/90 mm Hg was assigned to hypertensive patients who received antihypertensive drug therapy. Information on smoking and alcohol use was obtained by means of a staff-administered standardized questionnaire. Current smoking and drinking were defined as smoking at least 1 cigarette per day and consuming alcohol every day, respectively, during the prior 12 months.

Venous blood samples were collected after fasting for at least 12 hours. Serum creatinine levels were measured as part of a multiple chemistry profile (SMA20; Laboratory Corporation of America, Burlington, NC) using an enzymatic method. Estimated GFR (eGFR) was calculated to assess renal function using the equation proposed by Chronic Kidney Disease Epidemiology Collaboration.²¹

Statistical methods

Long-term burden of BP was measured as the area under the curve (AUC), calculated using the statistical models we previously developed.^22–24 Nonlinear growth curve parameters of SBP and DBP measured repeatedly at multiple time points from childhood to adulthood were estimated using a random-effects mixed model by SAS proc MIXED. The mixed model incorporates fixed and random effects and allows the intercept, linear and nonlinear parameters to vary from individual to individual. The random-effect coefficients represent the difference between the fixed-effect parameters and the observed values. This model also allows for repeated measurements and different numbers of unequally spaced observations across individuals. The model selection was based on the Akaike information criterion (AIC). The most parsimonious model was selected based on P-values of the independent variable (age) at the significance level of 0.05. Age and its higher-order terms were included one by one for model building. The higher-order terms of age were not included in the model if they were not significant or made lower-order terms not significant or did not improve the goodness-of-fit of the model based on AIC values. Age was centered to the mean age (20.1 years) to reduce the collinearity of age with its higher-order terms. The term age2 was divided by 10 and age3 by 20 to improve the model fitting. Cubic curves for SBP and DBP were fitted in race-sex groups. As shown in Figure 1, using SBP as an example, the AUC was calculated as the integral of the curve parameters during the follow-up period for each subject. Because subjects had different follow-up periods, the AUC values were divided by the number of follow-up years and used for the association analyses.

Figure 1.

Illustration of the area under the curve (AUC) of SBP. a = incremental AUC; b = baseline AUC; total AUC = a + b. Abbreviation: SBP, systolic blood pressure.

Multivariable linear regression analyses were performed to examine the association of eGFR with BP in terms of childhood values (the first measurement), adulthood values (the last measurement), and total AUC values by race, adjusted for sex and adult age, BMI, smoking, and alcohol drinking. Before the regression analysis, childhood, adulthood, and AUC values were adjusted for childhood age, adulthood age and average age, respectively, by regression residual analyses in race-gender groups and then standardized by Z-transformation (mean = 0, SD = 1).

RESULTS

Table 1 summarizes childhood, adulthood, and AUC values of study variables by race and sex. The mean levels of continuous variables were compared between race and sex groups, adjusting for age (except age itself). In childhood, sex and race differences were not significant except for sex difference (male > female) in SBP in whites and race difference (white > black) in BMI in males. In adulthood, race and sex differences in SBP, DBP, and BMI were significant except for no race differences in BMI and DBP in males. Hypertension showed significant sex difference (male > female) in whites and race difference (white < black) in females. Creatinine showed significant sex (male > female) and race differences (white < black). Blacks had significantly higher eGFR than whites for both sexes; black females had significantly higher eGFR than black males. Despite the race difference in eGFR, there were 3 black subjects with eGFR<30 ml/min/1.73 m², and no white subjects had GFR below this cut-off. Total AUC values of SBP and DBP showed significant race (white < black) and sex (male > female) differences except for no race difference in DBP among males.

Table 1.

Characteristics of study participants by race and sex

	White		Black		P for race difference
	Male (n = 743)	Female (n = 903)	Male (n = 378)	Female (n = 488)	Male	Female
Childhood (first exam)
Age (year)	9.7 (3.2)	9.6 (3.3)	9.5 (3.0)	9.2 (3.0)	0.179	0.023
BMI (kg/m2)	17.5 (3.3)	17.5 (3.4)	17.1 (3.1)	17.3 (3.4)	0.034	0.434
SBP (mm Hg)	100.1 (9.7)*	99.0 (9.9)	99.3 (11.0)	98.0 (10.3)	0.194	0.083
DBP (mm Hg)	61.1 (8.1)	61.3 (8.4)	61.9 (8.3)	61.0 (8.6)	0.132	0.488
Adulthood (last exam)
Age (year)	35.8 (8.7)	35.3 (8.8)	33.2 (9.4)	33.6 (9.1)	<0.001	0.001
BMI (kg/m2)	28.7 (6.2)†	27.8 (7.6)	28.0 (7.1)†	30.5 (8.6)	0.082	<0.001
SBP (mm Hg)	119.3 (13.2)†	112.1 (13.5)	124.0 (17.4)*	119.9 (18.5)	<0.001	<0.001
DBP (mm Hg)	80.1 (9.7)†	75.3 (9.3)	81.0 (13.3)†	78.9 (12.7)	0.220	<0.001
Creatinine (mg/dl)	1.00 (0.16)†	0.77 (0.13)	1.13 (0.60)†	0.82 (0.24)	<0.001	<0.001
eGFR (ml/min/1.73m2)	97.0 (14.9)	100.1 (15.9)	104.0 (19.5)†	110.9 (19.5)	<0.001	<0.001
Hypertension, n (%)	188 (25.3)†	172 (19.1)	114 (30.2)	143 (29.3)	0.083	<0.001
Smoker, n (%)	244 (32.8)	294 (32.6)	143 (37.8)*	125 (25.6)	0.097	0.007
Drinker, n (%)	264 (35.5)†	376 (41.6)	94 (24.9)†	163 (33.4)	<0.001	0.003
Total AUC
Average age (year)	20.9 (5.7)	20.8 (5.7)	19.3 (5.5)	19.6 (5.4)	<0.001	<0.001
SBP (mm Hg)	112.5 (7.7)†	107.6 (6.9)	114.4 (9.4)†	111.1 (8.7)	0.001	<0.001
DBP (mm Hg)	71.5 (6.0)†	69.6 (5.1)	71.5 (7.6)†	71.2 (6.5)	0.948	<0.001

Values are mean (SD) for continuous variables. Abbreviations: AUC, area under the curve; BMI, body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure.

*P < 0.05 and ^†P < 0.01 for sex difference within racial groups.

Table 2 presents standardized regression coefficients of adult eGFR on childhood, adulthood, and total AUC values of BP, adjusted for sex and adulthood age, BMI, smoking, and alcohol drinking in 3 separate regression models. Childhood values of SBP and DBP were not significantly associated with adult eGFR. Adult eGFR was significantly and negatively associated with adulthood and total AUC values of SBP and DBP in blacks, but not in whites. In addition, the differences in the regression coefficients of adulthood and total AUC values of SBP and DBP were significant between blacks and whites (P < 0.01).

Table 2.

Standardized regression coefficients of blood pressure from childhood on adult eGFR

Independent variable	White		Black		P for race difference
	β (SE)	P	β (SE)	P
Childhood
SBP	−0.04 (0.03)	0.136	−0.02 (0.04)	0.528	0.528
DBP	−0.04 (0.03)	0.131	0.04 (0.04)	0.300	0.300
Adulthood
SBP	0.01 (0.03)	0.782	−0.10 (0.04)	0.005	0.005
DBP	0.02 (0.03)	0.522	−0.11 (0.04)	0.003	0.003
Total AUC
SBP	−0.02 (0.03)	0.560	−0.10 (0.04)	0.005	0.005
DBP	−0.01 (0.03)	0.993	−0.09 (0.04)	0.013	0.013

All P values were adjusted for sex, adult age, BMI, smoking, and alcohol drinking. Abbreviations: AUC, area under the curve; β, standardized regression coefficient; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; SE, standard error.

Figure 2 presents mean levels of covariate-adjusted eGFR by quartiles of SBP and DBP, respectively, in terms of childhood, adulthood, and total AUC values by race. After adjusting for sex, adult age, BMI, smoking, and alcohol drinking, the mean levels of eGFR decreased across increasing quartiles of adulthood (P = 0.003 for trend) and total AUC (P = 0.024 for trend) values of SBP in blacks but not in whites. The eGFR values also showed decreasing trends across quartiles of adulthood (P = 0.030 for trend) and total AUC (P = 0.064 for trend) values of DBP in blacks. In addition, blacks with hypertension had lower eGFR than those without hypertension (P = 0.012) but not for whites (Figure 3).

Figure 2.

Covariate-adjusted eGFR by quartiles of SBP and DBP by race. Covariates included sex, adult age, body mass index, smoking, and alcohol drinking. Abbreviations: AUC, area under the curve; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure.

Figure 3.

Covariate-adjusted eGFR in normotension and hypertension in adults by race. Covariates included sex, adult age, body mass index, smoking, and alcohol drinking. Abbreviation: eGFR, estimated glomerular filtration rate.

DISCUSSION

In this community-based cohort study, we used the area under the growth curve as a measure of cumulative burden of BP from childhood to adulthood. We found that adulthood and total AUC values of SBP and DBP were significantly and negatively associated with eGFR in blacks but not in whites. There were no significant associations between childhood BP and adult eGFR in both blacks and whites. The findings from this study suggest that the black–white disparity in the association between renal function and BP begins in middle age.

Hypertension is one of the most important risk factors contributing to the development of CKD and ESRD.^8,25 A meta-analysis including 1,003,793 participants suggested that high-normal BP was associated with an increased risk of future ESRD compared with optimal BP²⁶. A large longitudinal study of middle-aged rural Chinese men and women showed that there was a dose–response relationship between baseline BP and renal function decline.²⁷ In addition, studies have shown that children with elevated BP had a higher prevalence of microalbuminuria,^28,29 indicating that BP-related renal damage has occurred in early life. It is well known that BP tracks from childhood into adulthood and childhood elevated BP predict adult hypertension. Several longitudinal cohort studies followed up from youth have provided evidence that elevated BP in early life plays an important role in the development of renal damage in later life. A longitudinal study with 40-year follow-up showed that elevated BP in late adolescence was an independent predictor of ESRD in middle age.¹² Another cohort study followed up from childhood indicated that high and middle pulse pressure trajectories in early life predicted an increased risk of subclinical renal insufficiency at age 30 years.¹³ Our previous study found that elevated BP in childhood was significantly associated with microalbuminuria in adulthood in blacks, but not in whites.¹⁰ In the present study, all values of BP were not associated with adult eGFR in whites; eGFR was significantly associated with total AUC and adult values of BP but not with childhood BP in blacks. The lack of the association between childhood BP and adult eGFR in blacks may be explained by the relatively limited statistical power of the sample size to detect the weak-to-moderate associations. Future studies with larger samples are required to investigate this association.

A large body of evidence has suggested that blacks vs. whites experience a disproportionate burden of ESRD in the United States.^1,30,31 In 2015, the prevalence of ESRD was about 3.7 times greater in blacks compared with whites.¹ It should be noted that although the mean values of eGFR were higher in blacks than in whites in our study, the 3 subjects with CKD stage 4 or 5 (eGFR < 30 ml/min/1.73 m²) were all blacks, and no whites had such a low eGFR. In line with these findings, a previous study of young adults reported similar results showing that blacks vs. whites had higher levels of eGFR, but higher prevalence of CKD at stages 4 or 5.³² The results from previous studies and ours support the hypothesis that blacks have higher filtration function of the kidney in the early phase, but a steeper decline in eGFR and faster progression from CKD to ESRD.³⁰ One potential explanation for racial disparity of ESRD burden is that blacks have markedly higher prevalence of hypertension,^33,34 diabetes,³⁵ and other related risk factors than whites. However, studies have indicated that the excessive incidence of ESRD in blacks is not completely explained by differences in the prevalence of these risk factors.³⁶

A study showed that blacks had 2.3-fold higher prevalence of microalbuminuria in hypertensives than whites.³⁷ Our previous study indicated that black adults had significantly higher prevalence of microalbuminuria than whites; childhood BP and its rate of change from childhood to adulthood were significantly associated with adult microalbuminuria in blacks but not in whites.¹⁰ In the present study, BP measured in adulthood and as a cumulative burden from childhood to adulthood were significantly and negatively associated with adult eGFR in blacks but not in whites. These observations suggest that blacks might be more susceptible to BP-related renal damage and dysfunction than whites. Renal hemodynamic and anatomic differences between black and white hypertensive patients may be responsible for racial disparity in the association between BP and renal dysfunction. For instance, black hypertensive patients have a greater reduction in renal blood flow as well as more severe nephrosclerosis than white patients.³⁸ In addition, salt sensitivity is associated with increased albumin excretion and glomerular capillary pressure,³⁹ and black hypertensive subjects are more likely to be salt sensitive than white hypertensives.⁴⁰

This community-based longitudinal cohort study provides a unique opportunity to examine the racial difference in the association between BP measured from childhood to adulthood and renal function in adulthood. However, there were several limitations in the present study. First, estimated GFR based on serum creatinine remains relatively imprecise, and more accurate filtration markers such as cystatin C, beta-trace protein or b2-microglobulin were unavailable and thus not examined. Second, hypertensive subjects with pharmacological treatment represent a subgroup who would be expected to have the highest BP levels without treatment; therefore, the forced BP values of these participants may result in bias in the growth curve parameter estimation. Third, physical activity, dietary data, and other risk factors of renal dysfunction were not or partly available in the present cohort. Their influences on the observed association could not be examined.

In summary, this longitudinal study demonstrated race difference in the impact of long-term burden of BP from childhood to adulthood on the development of renal dysfunction between whites and blacks. The development of race-specific prevention and intervention strategies should be encouraged for controlling BP to reduce the risk of renal disease in adult life.

DISCLOSURE

The authors declared no conflict of interest.