Abstract
African Americans have a wide range of continental genetic ancestry. It is unclear whether racial differences in blood pressure (BP) control are related to ancestral background. The authors analyzed data from the Jackson Heart Study, a cohort exclusively comprised of self‐identified African Americans, to assess the association between estimated West African ancestry (WAA) and BP control (systolic and diastolic BP < 140/90 mm Hg). Three nested modified Poisson regression models were used to calculate prevalence ratios for BP control associated with the three upper quartiles, separately, vs the lowest quartile of West African ancestry. The authors analyzed data from 1658 participants with hypertension who reported taking all of their antihypertensive medications in the previous 24 hours. WAA was estimated using 389 ancestry informative markers and categorized into quartiles (Q1: <73.7%, Q2: >73.7%‐81.0%, Q3: >81.0%‐86.3%, and Q4: >86.3%). The proportion of participants with controlled BP in the lowest‐to‐highest WAA quartile was 75.2%, 76.1%, 76.6%, and 74.4%. The prevalence ratios (95% CI) for controlled BP comparing Q2, Q3, and Q4 to Q1 of WAA were 1.00 (0.93‐1.08), 1.02 (0.94‐1.10), and 0.99 (0.91‐1.07), respectively. Among African Americans in the Jackson Heart Study taking antihypertensive medication, BP control rates did not differ across quartiles of WAA.
Keywords: African Americans, blood pressure control, hypertension, medication, treatment
What this study adds?
In this cross‐sectional study of self‐identified African Americans taking antihypertensive medication in the JHS, BP control rates were not statistically significantly different across quartiles of percent of estimated global West African ancestry.
This suggests that genetic factors differentially distributed by continental ancestry may not account in large part for the lower proportion of African Americans than European Americans with controlled BP.
1. INTRODUCTION
Among adults taking antihypertensive medication, African Americans have lower rates of controlled blood pressure (BP) compared with European Americans.1 The reasons underlying this disparity are complex, involving sociocultural, patient, and provider factors.2, 3, 4, 5, 6 Potential reasons include, but are not limited to, racial differences in medication adherence, clinical inertia, social conditions, discrimination, the underlying biology of hypertension, medication responses, psychosocial, and behavioral factors such as diet and physical activity.2, 3, 4, 5, 6 African Americans have a wide range of continental genetic ancestry with varying degrees of African, Native American, and European genetic ancestry, and it is unclear whether continental ancestry is associated with BP control among adults taking antihypertensive medication.7, 8
Genetic ancestry‐based approaches utilize genetic markers with large allele frequency differences between ancestral groups, called ancestry informative markers (AIMS), to uncover genetic variation contributing to an observed racial difference in a particular phenotype.9, 10, 11 Prior studies have shown that the percent of estimated global West African ancestry among modern‐day self‐identified African Americans ranges from 30% to 100% with an average of 73%.7 The wide range of West African ancestry among self‐identified African Americans provides an opportunity to determine the degree to which genetic ancestry accounts for the lower prevalence of BP control in African Americans compared with European Americans. We therefore determined the association between estimated global West African genetic ancestry and BP control using data from the Jackson Heart Study (JHS), a cohort comprised exclusively of self‐identified African Americans. We hypothesized that participants with a higher percent of estimated global West African ancestry would be less likely to have controlled BP.
2. METHODS
2.1. Study population
The purpose of the JHS was to investigate the reasons for the high risk of CVD among African Americans and to identify potential approaches for reducing this risk.12 The JHS is one of the few African American‐specific cohort studies with high‐quality measures of BP and extensive genetic data. The JHS enrolled 5306 non‐institutionalized self‐identified African Americans, 21 years, and older between 2000 and 2004. The current cross‐sectional study was restricted to 1658 JHS participants at Examination 1 who had genetic ancestry information available, had valid BP data from the baseline study visit, taking at least one class of antihypertensive medication, and self‐reported taking all of their antihypertensive medications within the past 24 hours (Figure 1). The 24‐hour self‐reported antihypertensive medication adherence measure has been associated with BP control in the JHS.13 The JHS protocol was approved by the University of Mississippi Medical Center's Institutional Review Board. The current analysis was approved by the University of Utah's Institutional Review Board. All JHS participants provided written informed consent.
Figure 1.
Jackson Heart Study participant flowchart for the current analysis. BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure
2.2. Data collection
Data for the current analysis were collected at Examination 1. Trained study staff administered questionnaires during an in‐home interview to collect self‐reported information on sociodemographics, CVD risk factors, and socioeconomic factors. At a subsequent clinic examination, trained technicians measured each participant's height, weight, and BP, collected blood samples, and conducted a pill bottle review of all medications taken in the 2 weeks preceding the clinic examination.
2.3. Antihypertensive medication use
Jackson Heart Study participants were instructed to bring all of their prescribed and over‐the‐counter medications they had taken in the last 2 weeks to their study visit. Trained study staff recorded the names of each medication and asked whether they had taken them in the previous 24 hours. The following drug classes were recorded as antihypertensive medications: angiotensin‐converting enzyme inhibitor (ACEIs), aldosterone receptor antagonists, alpha blockers, angiotensin II receptor blockers (ARBs), beta blockers, calcium channel blockers, centrally acting agents, direct‐acting vasodilators, direct renin inhibitors, loop diuretics, potassium‐sparing diuretics, and thiazide diuretics. Single‐pill combination medications were separated into their individual classes.
2.4. West African ancestry
Using the software ADMIXTURE, percent of estimated global West African ancestry was quantified in each participant as the proportion of the genome with West African ancestry using a maximum‐likelihood‐based modeling procedure assuming K = 3 founding populations.14 Three datasets comprised the reference populations: 114 individuals from HapMap15 YRI (Yoruba in Ibadan, Nigeria) representing West African ancestry, 117 individuals from HapMap15 CEU (Utah residents with ancestry from northern and western Europe from the CEPH collection) representing European ancestry, and 21 Maya and 14 Pima individuals from the Human Genome Diversity Project (HGDP)16 representing Native American ancestry. We merged 2224 AIMS available in the JHS with the genotypes from the three reference populations.17 These autosomal AIMS are validated and have been used previously to estimate continental ancestry information in admixed populations.17 In particular, the Nigerian parental population (ie, HapMap YRI) is a very useful proxy for West African ancestry as these markers vary widely across continental populations but not within West and Central Africans.18, 19 We filtered the AIMS to those with a genotype call rate ≥95%. After filtering, a total of 389 unlinked AIMS were obtained for estimating genetic ancestry. This number of AIMS is sufficient for estimating global West African ancestry among self‐identified African Americans as prior studies show that a correlation coefficient of >0.90 between estimated ancestry and true individual ancestry when the ancestry estimates are derived from 100 AIMs or more.20, 21 As there was little variation in the percentage of Native American ancestry among participants in the JHS (median [25th, 75th percentile]: 4.3% [0.0%, 9.7%]), only West African ancestry was investigated.
2.5. Clinic BP
Blood pressure was measured by trained staff during the baseline examination using an appropriate sized cuff and a standard Hawksley random zero sphygmomanometer (Hawksley and Sons Limited) after the participant had rested for at least 5 minutes. Two BP measurements were taken 1 minute apart. The random zero BP measurements were calibrated to a semi‐automated device (Omron HEM‐907XL, Omron Healthcare Inc) using robust regression as previously described.22 Mean systolic BP and diastolic BP were calculated using the calibrated measurements. BP control was defined as mean clinic systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg as these BP levels were the guideline recommendation at the time the JHS Examination 1 was conducted (2000‐2004).23
2.6. Ambulatory BP (ABPM)
Of the 5306 JHS participants at Examination 1, a total of 1148 performed 24‐hour ABPM using a SpaceLabs 90207 oscillometric device using an appropriate sized cuff.24 Measurements were taken every 20 minutes over a 24‐hour monitoring period. Using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes (IDACO) criteria, daytime was defined as 10 am to 8 pm and nighttime was 12 am to 6 am 25 Participants with at least 10 daytime and five nighttime systolic BP and diastolic BP measurements were considered to have a complete ABPM recording for the current analysis.
2.7. Covariates
Information on age, sex, annual household income, highest level of education achieved, antihypertensive medication use, and a history of myocardial infarction and stroke was obtained during the study interview. Duration of hypertension was defined by the age of each participant at Examination 1 minus the age at which they reported first having been told they had hypertension. Physical activity, smoking status, chronic stress, and daily and lifetime discrimination were ascertained using validated instruments as described previously.26, 27, 28 Body mass index (BMI) for each participant was calculated as weight in kilograms divided by height in meters squared. The pill bottle review was used to determine statin use. Diabetes was defined by a fasting (≥8 hours) serum glucose ≥126 mg/dL, hemoglobin A1c ≥6.5%, or use of insulin or oral glucose‐lowering medication within 2 weeks prior to the clinic examination. High‐sensitivity C‐reactive protein (CRP) was calculated using a latex particle immunoturbidimetric assay. The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation was used to calculate estimated glomerular filtration rate (eGFR).29 Reduced eGFR was defined by levels <60 mL/min/1.73 m2. Serum aldosterone levels were measured using radioimmunoassay (Siemens).
2.8. Statistical analysis
The distribution of percent of estimated global West African ancestry for participants included in the analysis was calculated. Characteristics were calculated for the overall study population and after grouping participants into quartiles of percent of estimated global West African ancestry. The percentage of participants with controlled BP was calculated by quartile of West African ancestry. Three nested modified Poisson regression models were used to calculate prevalence ratios for BP control associated with the three upper quartiles, separately, vs the lowest quartile of West African ancestry. Model 1 included adjustment for age, sex, and duration of hypertension. Model 2 included adjustment for variables in Model 1 and physical activity, smoking status, BMI, diabetes, statin use, ACEI/ARB use, beta‐blocker use, calcium channel blocker use, diuretic use, other antihypertensive medication use (ie, alpha blockers, renin inhibitors, or aldosterone receptor antagonists, centrally acting agents, and direct‐acting vasodilators), C‐reactive protein ≥3 mg/L, serum aldosterone levels, eGFR, history of myocardial infarction, and history of stroke. Model 3 included variables in Model 2 and socioeconomic and psychosocial factors including annual income <$25 000, having less than a high school education, global perceived stress scale score, insurance status, daily discrimination score, and lifetime discrimination score. We performed five secondary analyses. First, because it is hypothesized that the African American–European American difference in BP‐lowering response to ACEI and/or ARB medications is negated once other classes of antihypertensive medications are added, all analyses were repeated restricted to participants taking an ACEI or an ARB and no other antihypertensive medications.30, 31, 32, 33 Second, we repeated the analyses for participants taking and not taking an ACEI or an ARB, separately, regardless of the total number of antihypertensive medications they were taking. Third, we repeated the analyses stratified by the number of antihypertensive medication classes being taken. Fourth, the prevalence ratios, adjusted for the variables in model 3 described above, for BP control associated with percentage of West African ancestry, modeled as a continuous variable, were calculated using a restricted cubic spline. Fifth, using the ambulatory BP data available in 357 study‐eligible JHS participants, we calculated prevalence ratios for sustained BP control, defined as the presence of both clinic BP control (ie, systolic BP < 140 and diastolic BP < 90 mm Hg) and daytime BP control on ABPM (ie, daytime systolic BP < 135 and diastolic BP < 85 mm Hg), associated with the three upper quartiles, separately, vs the lowest quartile of West African ancestry. All analyses were conducted using Stata Version 14.
3. RESULTS
3.1. Participant characteristics
Among the 1658 participants included in the current analysis, the median [interquartile range] of West African ancestry was 81.0% [73.7%‐86.3%] (Figure 2). The four quartiles for percentage of West African ancestry were 23.3%‐73.7% (quartile 1), >73.7%‐81.0% (quartile 2), >81.0%‐86.3% (quartile 3), and >86.3%‐99.8% (quartile 4), respectively. The mean age of the overall population was 60.0 ± 10.8 years, and 32.5% of participants were male (Table 1). Characteristics of participants were not statistically significantly different across the quartiles of West African ancestry except for age (ie, lower age in higher quartiles of West African ancestry) and percentage with income ≥$50 000/y, higher BMI, and lifetime discrimination with progressively higher West African ancestry.
Figure 2.
Distribution of the percent of estimated global West African ancestry among Jackson Heart Study participants (n = 1658). Estimates of percentage of West African ancestry were calculated by ADMIXTURE with references from HapMap3 + HGDP, assuming K = 3
Table 1.
Characteristics of Jackson Heart Study participants, overall and by quartile of West African ancestry
| Characteristics | Overall (n = 1658) | Quartiles of percent African ancestry | P value | |||
|---|---|---|---|---|---|---|
| Q1 (23.3%‐73.7%) (n = 415) | Q2 (>73.7%‐81.0%) (n = 414) | Q3 (>81.0%‐86.3%) (n = 415) | Q4 (>86.3%‐99.8%) (n = 414) | |||
| West African ancestry, %, median (IQR) | 81.0 (73.7‐86.3) | 67.1 (60.9‐71.0) | 77.9 (75.8‐79.6) | 83.8 (82.4‐85.0) | 89.6 (87.8‐91.8) | <.001 |
| Age, y, mean ± SD | 60.0 ± 10.8 | 61.3 ± 10.5 | 58.7 ± 10.7 | 59.5 ± 11.4 | 60.5 ± 10.4 | .003 |
| Male, n (%) | 539 (32.5) | 145 (34.9) | 147 (35.5) | 126 (30.4) | 121 (29.2) | .126 |
| BMI, kg/m2, mean ± SD | 32.7 ± 7.2 | 32.0 ± 7.3 | 32.8 ± 7.0 | 33.4 ± 7.2 | 32.8 ± 7.3 | .048 |
| Smoking, n (%) | 184 (11.2) | 41 (10.0) | 51 (12.5) | 46 (11.2) | 46 (11.1) | .745 |
| Physical activity, n (%) | 881 (53.1) | 195 (47.0) | 224 (54.1) | 233 (56.1) | 229 (55.3) | .100 |
| History of MI, yes, n (%) | 142 (8.6) | 30 (7.2) | 37 (8.9) | 43 (10.4) | 32 (7.7) | .377 |
| History of stroke, yes, n (%) | 117 (7.1) | 29 (7.0) | 29 (7.0) | 32 (7.7) | 27 (6.5) | .928 |
| Statin use, yes, n (%) | 342 (20.6) | 81 (19.5) | 94 (22.7) | 85 (20.5) | 82 (19.8) | .664 |
| Diabetes, yes, n (%) | 549 (33.2) | 117 (28.3) | 138 (33.3) | 147 (35.4) | 147 (35.6) | .093 |
| eGFR, mL/min/1.73 m2, mean ± SD | 87.1 ± 22.6 | 87.5 ± 22.2 | 87.9 ± 24.0 | 85.6 ± 23.1 | 87.3 ± 20.8 | .479 |
| Income: ≥$50 000/y, n (%) | 425 (30.1) | 139 (38.4) | 105 (30.4) | 96 (27.0) | 85 (24.4) | <.001 |
| GPSS, mean ± SD | 4.8 ± 4.3 | 4.8 ± 4.2 | 4.8 ± 4.3 | 4.9 ± 4.4 | 4.8 ± 4.4 | .963 |
| Lifetime discrimination, median (IQR) | 1.8 (1.2, 2.4) | 1.6 (1.1, 2.2) | 1.8 (1.2, 2.6) | 1.8 (1.2, 2.6) | 1.8 (1.2, 2.4) | .041 |
| Total discrimination, median (IQR) | 3.0 (1.0, 4.0) | 3.0 (1.0, 4.0) | 3.0 (1.0, 5.0) | 3.0 (1.0, 4.0) | 3.0 (1.0, 4.0) | .171 |
| Clinic SBP, mm Hg, mean ± SD | 130.2 ± 16.0 | 130.3 ± 15.2 | 130.0 ± 16.0 | 129.7 ± 16.1 | 130.6 ± 16.7 | .870 |
| Clinic DBP, mm Hg, mean ± SD | 75.7 ± 8.9 | 75.2 ± 8.7 | 76.2 ± 8.5 | 75.2 ± 9.5 | 76.0 ± 8.9 | .235 |
| Aldosterone concentration, ng/dL, median (IQR) | 5.3 (3.1‐8.8) | 5.5 (3.2‐8.8) | 5.3 (3.2‐9.1) | 5.2 (2.9‐9.4) | 5.2 (3.3‐8.1) | .106 |
| Number of antihypertensive medication classes | ||||||
| 1, n (%) | 530 (32.0) | 143 (34.5) | 130 (31.4) | 119 (28.7) | 138 (33.3) | .111 |
| 2, n (%) | 670 (40.4) | 172 (41.4) | 155 (37.4) | 169 (40.7) | 174 (42.0) | |
| 3, n (%) | 306 (18.5) | 71 (17.1) | 80 (19.3) | 81 (19.5) | 74 (17.9) | |
| 4+, n (%) | 152 (9.2) | 29 (7.0) | 49 (11.8) | 46 (11.1) | 28 (6.8) | |
| Calcium channel blocker, n (%) | 616 (37.2) | 148 (35.7) | 172 (41.6) | 154 (37.1) | 142 (34.3) | .154 |
| Diuretic, n (%) | 1049 (63.3) | 249 (60.0) | 275 (66.4) | 262 (63.1) | 263 (63.5) | .296 |
| Beta blocker, n (%) | 392 (23.6) | 98 (23.6) | 93 (22.5) | 105 (25.3) | 96 (23.2) | .802 |
| Angiotensin‐converting enzyme inhibitors, n (%) | 640 (38.6) | 144 (34.7) | 166 (40.1) | 176 (42.4) | 154 (37.2) | .115 |
| Angiotensin receptor blockers, n (%) | 268 (16.2) | 73 (17.6) | 61 (14.7) | 64 (15.4) | 70 (16.9) | .663 |
| Aldosterone receptor antagonist, n (%) | 37 (2.2) | 9 (2.2) | 9 (2.2) | 13 (3.1) | 6 (1.4) | .437 |
| Alpha 1 antagonists, n (%) | 112 (6.8) | 31 (7.5) | 32 (7.7) | 23 (5.5) | 26 (6.3) | .556 |
| Alpha 2 agonists and other centrally acting agents, n (%) | 89 (5.4) | 18 (4.3) | 27 (6.5) | 24 (5.8) | 20 (4.8) | .507 |
| Duration of hypertension, y, median (IQR) | 12.1 (4.4‐22.8) | 11.9 (4.2‐22.6) | 11.7 (4.5‐22.7) | 10.5 (4.0‐21.1) | 14.3 (5.3‐24.3 | .175 |
Total physical activity ranges from 1 to 5 and is from four domains (active living, work, home life, and sport) and was assessed using a validated survey.
Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; GPSS, global perceived stress scale; IQR, interquartile range; MI, myocardial infarction; mm Hg, millimeter of mercury; SBP, systolic blood pressure; SD, standard deviation.
3.2. BP control
Overall, 75.6% of participants taking antihypertensive medication had controlled BP. The proportion of participants with controlled BP from lowest to highest quartile of West African ancestry was 75.2%, 76.1%, 76.6%, and 74.4% (Table 2). There was no association between percentage of West African ancestry and BP control across quartiles of West African ancestry following adjustment for age, sex, duration of hypertension, and after further adjustment for cardiovascular and psychosocial risk factors. In the fully adjusted model, the prevalence ratios (95% CI) for BP control associated with quartiles 2, 3, and 4 compared with quartile 1 of West African ancestry were 1.00 (0.93‐1.08), 1.02 (0.94‐1.10), and 0.99 (0.91‐1.07) (P‐trend .88). The prevalence ratios for BP control for all covariates in the models are shown in Table S1.
Table 2.
Prevalence and prevalence ratios for blood pressure control associated with West African ancestry among African Americans taking antihypertensive medication in the Jackson Heart Study
| Quartiles of percent West African ancestry | P‐trend | ||||
|---|---|---|---|---|---|
| Q1 (23.3%‐73.7%) (n = 415) | Q2 (>73.7%‐81.0%) (n = 414) | Q3 (>81.0%‐86.3%) (n = 415) | Q4 (>86.3%‐99.8%) (n = 414) | ||
| N with controlled BP/N in quartile (Prevalence, %) | 312/415 (75.2%) | 315/414 (76.1%) | 318/415 (76.6%) | 308/414 (74.4%) | |
| Prevalence ratio (95% confidence interval) | |||||
| Model 1 | 1 (reference) | 1.00 (0.92, 1.08) | 1.01 (0.93, 1.08) | 0.99 (0.91, 1.07) | .79 |
| Model 2 | 1 (reference) | 1.00 (0.93, 1.08) | 1.02 (0.94, 1.10) | 0.99 (0.91, 1.07) | .85 |
| Model 3 | 1 (reference) | 1.00 (0.93, 1.08) | 1.02 (0.94, 1.10) | 0.99 (0.91, 1.07) | .88 |
Model 1: Adjustment for age, sex, and duration of hypertension. Model 2: Adjustment for variables in Model 1 and physical activity, smoking status, BMI, diabetes, statin use, ACEI/ARB use, beta‐blocker use, calcium channel blocker use, diuretic use, other antihypertensive medication use (ie, alpha blockers, renin inhibitors, or aldosterone receptor antagonists, centrally acting agents, and direct‐acting vasodilators), C‐reactive protein ≥3 mg/L, serum aldosterone levels, estimated glomerular filtration rate, history of myocardial infarction, and history of stroke. Model 3: Adjustment for the variables in Model 2 and socioeconomic and psychosocial factors (ie, annual income <$25 000, less than a high school education, global perceived stress scale score, daily discrimination score, and lifetime discrimination score).
Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure.
3.3. Secondary analyses
Among participants taking an ACEI or ARB as monotherapy (n = 162), 80.0%, 72.5%, 77.5%, and 64.9% in quartiles 1, 2, 3, and 4 of West African ancestry, respectively, had controlled BP (Table 3). After adjustment for the covariates in Model 3, the prevalence ratios (95% CI) for BP control associated with quartiles 2, 3, and 4 compared with quartile 1 were 0.85 (0.66‐1.09), 0.86 (0.67‐1.11), and 0.82 (0.60‐1.12) (P‐trend .21). Percentage of West African ancestry was not associated with BP control among participants taking or not taking an ACEI or ARB, analyzed separately (Table S2). The percentage of West African ancestry was also not associated with BP control among participants taking 1, 2, 3, or ≥4 classes of antihypertensive medication (Table S3). When modeled as a continuous variable using a cubic spline, West African ancestry was not associated with BP control (Figure S1). There was no evidence of associations between West African ancestry and sustained BP control in unadjusted or adjusted models (Table S4).
Table 3.
Prevalence and prevalence ratios for blood pressure control associated with West African ancestry among self‐identified African Americans taking one antihypertensive medication which was an ACEI or an ARB in the Jackson Heart Study (N = 162)
| Quartiles of percent West African ancestry | P‐trend | ||||
|---|---|---|---|---|---|
| Q1 (34.7%‐73.3%) (n = 45) | Q2 (73.8%‐80.9%) (n = 40) | Q3 (81.2%‐86.0%) (n = 40) | Q4 (86.4%‐96.0%) (n = 37) | ||
| N with controlled BP/N in quartile (Prevalence, %) | 36/45 (80.0%) | 29/40 (72.5%) | 31/40 (77.5%) | 24/37 (64.9%) | |
| Prevalence ratio (95% confidence interval) | |||||
| Model 1 | 1 (reference) | 0.88 (0.69, 1.11) | 0.95 (0.75, 1.19) | 0.80 (0.61, 1.07) | .19 |
| Model 2 | 1 (reference) | 0.90 (0.71, 1.16) | 0.91 (0.71, 1.17) | 0.85 (0.63, 1.15) | .30 |
| Model 3 | 1 (reference) | 0.85 (0.66, 1.09) | 0.86 (0.67, 1.11) | 0.82 (0.60, 1.12) | .21 |
Model 1: Adjustment for age, sex, and duration of hypertension. Model 2: Included adjustment for variables in Model 1 plus physical activity, smoking status, BMI, diabetes status, statin medication use, C‐reactive protein ≥3 mg/L, serum aldosterone levels, estimated glomerular filtration rate, history of myocardial infarction, and history of stroke. Model 3: Adjustment for the variables in Model 2 and socioeconomic and psychosocial factors (ie, annual income <$25 000, less than a high school education, global perceived stress scale score, daily discrimination score, and lifetime discrimination score).
Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure.
4. DISCUSSION
In this cross‐sectional study of self‐identified African Americans in the JHS who reported taking all of their antihypertensive medications, there was no evidence of a difference in the proportion with BP control across quartiles of percent of estimated global West African ancestry. There was no association after varying degrees of adjustment or when stratifying by the number of antihypertensive medication classes being taken. Although not statistically significant, the proportion of the population with controlled BP was numerically lower in higher quartiles of percentage of West African ancestry among the small subgroup of participants taking ACEI or ARB as monotherapy. Overall, the results of the current analysis show that West African genetic ancestry, which is a proxy for genetic variants that vary due to historical separations according to geographic origins and demographic history, is not associated with BP control among African Americans taking antihypertensive medication.
Although blood pressure has a high degree of heritability, genetic variants identified to date explain only a small percentage (~<3%) of the interindividual variation in blood pressure.34, 35, 36 Candidate gene and genome‐wide studies have identified pharmacogenetic variants associated with the BP‐lowering response to antihypertensive medications (particularly thiazide diuretics [NEDD4L] and beta blockers [ADRB1]) although the effect sizes of individual variants are quite small.37, 38, 39, 40, 41, 42, 43 However, the effectiveness of antihypertensive medication does vary by ancestral group (eg, African, Asian, and European ancestry), which may be related, in part, to genetic factors that vary in frequency according to historical geographic separations (ie, Europeans, Asians, and Africans living partially isolated in unique environments for tens of thousands of years).44 Modern‐day African Americans are a heterogeneous group and have a wide range of continental ancestry.10, 11 This variation in continental ancestry raises the question of whether the observed racial differences in BP control are related to an individual's ancestral background. The results of the current study imply that there is not a strong association between West African genetic ancestry and BP control among African Americans in the JHS who report taking all of their antihypertensive medications. The prospective cross‐over trial, Ancestry and biological Informative Markers for stratification of HYpertension: The AIM HY study, is currently ongoing and testing whether the BP‐lowering response to chlorthalidone, amlodipine, and lisinopril differs by levels of genetic ancestry among blacks and whites in the United Kingdom.45 In the interim, it may be judicious for clinicians to focus on the use of evidence‐based medication regimens and non‐pharmacologic factors proven to reduce BP, such as weight loss, physical activity, alcohol reduction, stress, and diet. Also, high‐quality clinic and out‐of‐clinic blood pressure measurements are critical to optimally manage high blood pressure.
Several randomized trials show that African Americans respond differently to certain classes of antihypertensive medications when compared to European Americans.6, 7 A meta‐analysis of 13 randomized controlled trials showed that African Americans, on average, have a 4.8 mm Hg lesser reduction in systolic BP following the initiation of ACEIs than do those with predominantly European ancestry.46 In a prespecified subgroup analysis of the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), chlorthalidone was superior to lisinopril for preventing stroke and CVD events in African Americans but not in European Americans.47 In ALLHAT, the greatest systolic BP change from baseline to 1 year among blacks was for those randomized to chlorthalidone (−7.7 mm Hg) compared with amlodipine (−5.7 mm Hg) and lisinopril (−2.5 mm Hg). In contrast, whites in ALLHAT experienced greater and more consistent systolic BP change at 1 year across randomization medications, chlorthalidone (−9.8 mm Hg) compared with amlodipine (−8.4 mm Hg) and lisinopril (−8.1 mm Hg). Similar findings were observed in the Losartan Intervention For Endpoint reduction in hypertension trial. Losartan was associated with reduced CVD risk compared with atenolol in non‐African Americans but increased CVD risk in African Americans.48 In a recent randomized trial in black sub‐Saharan Africans with uncontrolled BP taking 0 or 1 antihypertensive medications at baseline, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering clinic BP at 6 months of follow‐up.49 The Eighth Joint National Committee Panel (JNC8) Panel Member Report and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines recommend different classes of antihypertensive medications for African Americans and European Americans initiating pharmacologic therapy for hypertension.50, 51 Specifically, both the 2017 ACC/AHA BP guideline and the JNC8 Panel Member Report recommended non‐black adults initiate antihypertensive medication with a thiazide diuretic, calcium channel blocker (CCB), or ACEI, while black adults were recommended treatment initiation with a thiazide diuretic or CCB.51
This study has several strengths. The JHS provided a large sample of African Americans with genotype data and BP measured following a standardized protocol. The comprehensive data collected for a variety of risk factors related to BP control permitted adjustment for many potential confounders including medication adherence, obesity, smoking, stress, physical activity, and socioeconomic status. Results of this analysis should be interpreted in the context of potential limitations. BP was measured during a single visit, whereas current guidelines recommended obtaining measurements at a minimum of two visits and using out‐of‐clinic BP monitoring to confirm the BP levels. We did not evaluate the impact of gene‐environment interactions, individual genetic variants, or rare variants across the entire genome (ie, whole‐genome sequencing) that may have smaller effect sizes. There were a small number of study participants who were using either an ACEI or ARB as a monotherapy, and the subgroup analysis of West African ancestry and BP control may have been underpowered.
In conclusion, there was no association between West African ancestry and BP control in the current study of self‐identified African Americans taking antihypertensive medication. This suggests that genetic factors differentially distributed by continental ancestry do not account in large part for the lower proportion of African Americans than European Americans with controlled BP. Given this lack of association between West African genetic ancestry and BP control, differences in medication adherence, clinical inertia, or use of non‐pharmacologic therapies may be more likely to explain the racial differences in BP control.
CONFLICT OF INTEREST
Dr Muntner receives support to his institution from Amgen Inc unrelated to the current project. Dr Bress receives support to his institution from Novartis, Amgen, and Amarin unrelated to the current project.
AUTHOR CONTRIBUTIONS
Jon C Van Tassell, Rachel Hess, Rick Kittles, Paul Muntner, and Adam Bress provided design and concept of the study, serve as methodological expertise, analyzed and interpreted the data, and drafted the manuscript. James Wilson, Lynn Jorde, Man Li, Leslie A Lange, and Ethan Lange serve as methodological expertise, analyzed and interpreted the data, and drafted the manuscript.
Supporting information
ACKNOWLEDGMENTS
The authors thank the Jackson Heart Study team (University of Mississippi Medical Center, Jackson State University, and Tougaloo College) and study participants for their long‐term commitment and significant contributions to the study.
Van Tassell JC, Shimbo D, Hess R, et al. Association of West African ancestry and blood pressure control among African Americans taking antihypertensive medication in the Jackson Heart Study. J Clin Hypertens. 2020;22:157–166. 10.1111/jch.13824
Funding information
The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute for Minority Health and Health Disparities (NIMHD). The authors also wish to thank the staffs and participants of the JHS. This work was also supported by NIH National Heart, Lung, and Blood Institute R01HL117323 (PM). PM receives support through grant 15SFRN2390002 from the American Heart Association. Dr Bress receives support through grant K01HL133468 from the National Heart, Lung, and Blood Institute, Bethesda, MD. Dr Lynn Jorde receives support through grant R35‐GM118335 from the National Institute of General Medical Sciences (NIGMS). Dr Shimbo has received grant support from NHLBI (K24‐HL125704). Dr Jon Van Tassell was support by University of Utah College of Pharmacy for his PharmD Capstone Research Project.
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