Working Group on Research Needs to Improve Hypertension Treatment and Control in African Americans

Executive Summary

Despite important advances in knowledge related to prevention of hypertension and improvements in awareness treatment and control of hypertension in African Americans, much remains to be done. The following list provides recommendations that were felt to represent some of the most important research needs to facilitate improvements in prevention, treatment and control of hypertension among African Americans. The recommendations are grouped into broad categories. The order of the list is not intended to convey priority.

Report

Introduction

African Americans have long been recognized as a group of Americans with the highest prevalence and earliest onset of hypertension and associated increased risk of stroke, heart failure, renal failure, and death.  Much research has been conducted over the past several decades to address this important public health issue.  To leverage this investment of primarily public funds, the National Heart, Lung, and Blood Institute with a contribution from the National Institute of Diabetes, Digestive and Kidney Diseases, convened a 2-day working group to conduct a comprehensive assessment of the research that is needed to further improve prevention, treatment and control of hypertension among African Americans in order to prevent the devastating consequences of high blood pressure (BP).

This report presents the findings of an ad hoc working group assembled by the National Heart, Lung, and Blood Institute (NHLBI) to assess the research needed to improve prevention, treatment and control of hypertension among African Americans in the United Sates (US). There is considerable heterogeneity 1 but overall non-Hispanic Blacks (in this manuscript, the term African American is used for US studies whereas the term Black is used for international studies) have an earlier onset, higher prevalence, and disproportionately high risk of complications for hypertension, including stroke, heart failure, renal disease, and mortality compared to non-Hispanic Whites and Mexican Americans2,3.  Prior research has greatly improved our understanding of issues related to hypertension in African Americans, but important questions remain unanswered. As previously noted, this report complements a manuscript published in a November issue of Hypertension doi: 10.1161/HYPERTENSIONAHA.116.07905

Surveillance and measurement of BP

Surveys have identified substantial variation in mean BP levels among populations of African origin4. In many countries, including the US, mean BP and prevalence of hypertension are higher in adults self-described5-8 or observer reported9,10 as being black or having darker skin color11,12. Most such reports from Europe were based on studies in recent migrants13,14. In contrast, such a relationship is absent or only minimally apparent in several middle-income countries12,15,16. Research to clarify the reasons for this variability may contribute to our understanding of hypertension-related racial disparities in the US. In several US cross-sectional studies, psychosocial stress was related to perceived discrimination and residence in a stress-prone neighborhood was strongly correlated with hypertension17-21.

In US National Health and Nutrition Examination Survey (NHANES), crude and age-adjusted prevalence of hypertension in adults has remained fairly constant at about 30% since 1999-2000 when using the systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or taking antihypertensive medication definition of hypertension5,6,22. The corresponding overall estimate for prevalence in African Americans is about 40%, which has also remained fairly stable over the same time period. NHANES results may overestimate the prevalence of hypertension, because they are derived from a mean of three BP measurements obtained by a physician at a single visit, rather than a mean value based on two or more BPs obtained on two or more occasions, as recommended in Joint National Committee (JNC) guidelines23-25. In addition, out of office BP measurements suggest that somewhere between 15 to 30% of those designated as having hypertension using the NHANES diagnostic approach have “white coat hypertension”26,27. White coat hypertension appears to be associated with a much lower, albeit still elevated, risk of cardiovascular disease (CVD) events compared to “sustained hypertension”28.

In NHANES and many large NIH-funded observational studies and clinical trials, substantial effort is devoted to minimizing the errors associated with BP measurement by averaging multiple readings and quality control procedures. The degree to which recommendations for accurate measurement of BP and classification of hypertension are implemented in routine practice, and the extent to which measurement quality varies according to race, is uncertain and should be studied.

In African Americans, hypertension awareness and treatment rates are higher, but control rates lower, than in non-Hispanic Whites (85.7% vs. 82.7% for awareness, 77.4% vs. 76.7% for treatment, and 49.5% vs. 53.9% for control of hypertension in African American and White NHANES 2011-2012 participants, respectively)6. Despite use of a higher number of BP lowering medications and more treatment with thiazide diuretics, African Americans managed with antihypertensive medications in routine clinical practice have a lower BP control rate than the overall population in some studies29,30. This is in contrast to clinical trial experience, where the difference in BP control rates by race/ethnicity has been considerably reduced or eliminated, particularly with chlorthalidone-based treatment31,32. Substantial improvements in hypertension control rates, including in African Americans33,34, have been noted in large integrated health systems such as the Department of Veterans Affairs (VA) system33 and Kaiser Permanente in Northern35,36 and Southern California34.

Optimization of hypertension prevention and treatment in African Americans needs to be further explored. US regional observational cohort studies provide information regarding psychosocial factors, lifestyle habits, and medication beliefs – all of which have been associated with risk of hypertension and are potential targets for additional research, including intervention studies. The Bogalusa Heart Study37, which allows for lifespan contrasts between African Americans and Whites, the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, which provides a large geographically diverse cohort of White and African American US adults38, and the Jackson Heart Study39, which allows evaluation of a large sample of adult African Americans, are examples of studies that provide special opportunities to answer questions regarding BP in African Americans. In addition to study of those who develop hypertension, it is also important to investigate those whose BP remains within the normal range despite being exposed to environmental factors that predispose to high BP.   

Pathophysiology and genetic basis of hypertension in Blacks – a global perspective

With the exception of APOL 1 variants in patients with chronic kidney disease (CKD), genome-wide association studies have yielded limited insights into racial disparities in CVD morbidity and mortality, including hypertension40. Given the history of race relations in the United States and the likelihood that multiple genes are involved in the origins of elevated BP, environmental, behavioral and psychosocial factors likely play a more important role than genetics in the observed higher prevalence of hypertension in African Americans40. Interventions that target these factors and their biological effects may provide the most promising pathways to achievement of better BP control and CVD health in African Americans.

Lifestyle change and other non-pharmacologic interventions to prevent and treat hypertension

Nonpharmacological interventions, including reduced sodium and increased potassium intake, weight loss, higher levels of physical activity, and adoption of a healthy diet such as the Dietary Approaches to Stop Hypertension (DASH) diet have been shown to lower BP and treat hypertension in adult African Americans23,41. However, the body of evidence related to nonpharmacological interventions in African Americans is limited, especially for randomized controlled trials (RCTs) of physical activity42, potassium supplementation43, and reduced alcohol consumption44. With the exception of the Prevention and Treatment of Hypertension Study (PATHS) trial45, few Black participants are likely to have been included in trials that studied the effects of reduced alcohol intake on BP44. Dietary sodium reduction46,47, potassium supplementation43 and institution of the DASH diet48 result in greater lowering of BP in African Americans compared to Whites, at least in efficacy trials. There has been little study, albeit considerable speculation, surrounding the basis for these differences.

Nonpharmacological interventions, especially lifestyle changes, are best implemented by means of a combination of population-based approaches that seek to achieve a small downward shift in the community’s distribution of BP and more intensive approaches in individuals and high risk groups aimed at a greater reduction in BP. Individualized approaches may prove to be useful in counseling those at high risk for developing hypertension and its complications, such as target organ damage and premature mortality. Models for culturally appropriate evidence-based lifestyle modification are being evaluated and may provide a template for therapeutic lifestyle change in African Americans49,50. A gradual but progressive reduction in the amount of sodium added to food products represents the least onerous nonpharmacological intervention for the general population, including African Americans, and offers great potential for success51.

Potassium supplementation is an intervention that shows great promise, especially in African Americans52 and those consuming excessive amounts of sodium, but it has not been sufficiently tested in long term RCTs43,53. More research is needed to understand the efficacy of potassium supplementation, alone and in combination with reduced sodium, as an intervention to lower BP and to possibly mitigate thiazide-related increases in serum glucose in African American populations54. Likewise, more research is needed to understand the long-term safety of potassium interventions, especially in African Americans and other populations who have a higher than average prevalence of reduced kidney function or may be receiving antihypertensive treatments that impair renal excretion of potassium.

Major clinical outcomes in hypertension treatment trials

Many large RCTs have demonstrated the efficacy of antihypertensive therapy compared to placebo or usual care for reducing the risk of stroke (by about 40%), heart failure (by about 50%), and all-cause mortality (by about 20%). African Americans were well represented in the early antihypertensive drug treatment trials sponsored by the VA55,56 and NHLBI57,58, which evaluated stepped care based on initial therapy with thiazide or thiazide-like diuretics compared with placebo or usual care. These trials showed similar benefits in African American and White participants. The 1990s ushered in an era of comparative efficacy and effectiveness trials. Among these, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)59 is the only event-based trial to have compared thiazide-type diuretic with other first-step antihypertensive drug therapies in African Americans during long-term follow-up. Overall, there was no evidence of superiority for prevention of CVD outcomes during first step therapy with the angiotensin converting enzyme inhibitor (ACE-I) lisinopril, calcium channel blocker (CCB) amlodipine or the α-receptor blocker doxazosin, compared to the thiazide-type diuretic chlorthalidone in the more than 15,000 African Americans enrolled in ALLHAT. Chlorthalidone was superior to amlodipine, lisinopril and doxazosin for prevention of new-onset heart failure in both African Americans and Whites. In African Americans, but not in Whites, chlorthalidone was more effective than lisinopril for prevention of stroke, likely due in part to a greater reduction in BP. A lack of protection against stroke was also reported during treatment with the angiotensin receptor blocker (ARB) losartan compared to the β-blocker atenolol in the 533 Black (523 African American) Losartan Intervention For Endpoint reduction in hypertension (LIFE) clinical trial participants60, with similar treatment-related reductions in BP by race.

Little is known about the mechanisms responsible for the beneficial effects of chlorthalidone on CVD risk beyond its diuretic properties, and this should be investigated. This is especially the case because the most commonly used diuretic in the US, hydrochlorothiazide, may have a different level of efficacy61,62. In ALLHAT, there was no difference in the effect of treatment assignment on incidence of heart failure across race groups during the randomized treatment phase. However, when the post-trial follow-up experience was included (mean follow-up of 8.8 years), the hazard ratio for heart failure associated with randomization to amlodipine compared to chlorthalidone remained significantly higher in African Americans, but not in other ALLHAT subgroups (nominally significant race by treatment interaction). It is possible that African Americans continued on amlodipine while Whites were switched to other drugs. Whether choice of drugs for pharmacotherapy of hypertension differed by race after the randomized treatment phase of the ALLHAT study had been completed and participants once again obtained their care in the community could be explored.

Hypertension is common among African Americans and so is renal disease. African Americans suffer from end stage renal disease (ESRD) at a rate that is three times higher than Whites, constituting 13% of the US general population but more than 32% of all patients in the US receiving dialysis for kidney failure63. In the African American Study of Kidney Disease and Hypertension (AASK), antihypertensive treatment based on use of the ACE-I ramipril in patients with non-diabetic CKD was superior to corresponding treatment with the β-blocker metoprolol or CCB amlodipine in slowing the progression of CKD despite a 3 mm Hg higher achieved SBP compared to amlodipine64. However, in ALLHAT, first-step antihypertensive drug treatment based on use of the ACE-I lisinopril was not superior to either chlorthalidone or amlodipine-based therapy in preventing ESRD in African American participants65. These results need to be reconciled across the spectrum of renal disease.

It is well established that African Americans have higher levels of albuminuria compared to Whites66. The effects of a lower BP goal in the AASK were inconclusive but there was a suggestion that a lower BP goal might be beneficial in preventing renal disease outcomes in those with proteinuria.64,67 This possibility should be explored in other BP lowering trials with a substantial number of African American participants, such as the Systolic Blood Pressure Intervention Trial (SPRINT)68. The effects of various antihypertensive medications on renal disease outcomes may also differ for African Americans with albuminuria, in whom the role of renin angiotensin system (RAS) inhibitors is better defined, compared to those without albuminuria. However, the available RCT evidence is inconclusive. The use of dual RAS inhibition, with ACE-I and angiotensin receptor blocker (ARB) agents, lowered BP and albuminuria more than either drug alone in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), but it was associated with increased risk for several adverse outcomes, including acute kidney injury, renal disease progression, syncope, and hypotensive events69. Unfortunately, the subgroup with African ethnicity in ONTARGET was small (only 2.4% of the study sample). The findings in ONTARGET were also noted in a subsequent meta-analysis70. In the REGARDS study, the association of albuminuria with stroke risk was stronger for African Americans compared to Whites71. However, there are few data evaluating whether the presence of albuminuria modifies the effect of BP interventions aimed at reducing stroke, heart failure and mortality risk among African Americans.

Despite mean control of SBP/DBP to 133/78 mm Hg and use of ACEI in >80% during long-term follow-up (≥7 years) of 1,094 AASK participants, 54% experienced a doubling of serum creatinine, ESRD or death72. Therefore, there is an urgent need to develop novel therapeutic interventions for African Americans with hypertension and CKD.

Observational studies have demonstrated that the risk of stroke associated with a unit higher level of SBP is greater in African Americans compared with Whites73,74. However, in SPRINT, there was no evidence of a significant interaction between race (Black versus Non-Black) and treatment effect for the composite primary outcome, which included both ischemic and hemorrhagic stroke68.

Higher visit-to-visit BP variability (VVV) is associated with an increased risk for CHD, stroke, heart failure and mortality75. African Americans have higher VVV compared to Whites, which may be due to abnormal autonomic function, abnormal baroreflex function, or altered sodium excretion75. Whether VVV itself may become a therapeutic target or inform drug selection has yet to be determined. African Americans also have a very high prevalence of nocturnal hypertension (nighttime systolic/diastolic BP ≥ 120/70 mm Hg) and non-dipping blood pressure (decline in BP from daytime to nighttime ≤ 10%)76, especially those with a lower socioeconomic status77. The mechanisms underlying the night time elevation in BP among African-Americans remain poorly understood although several reports have identified the self-reported experience of racism or perceived ethnic discrimination as predictive of the absence of nocturnal dipping20,78,79.  Studies comparing the effects of antihypertensive drugs with a longer compared to shorter half-life (e.g. chlorthalidone compared to hydrochlorothiazide), the effects of bedtime dosing with antihypertensive medication on stroke, heart failure and mortality risk, and the effects of non-pharmacologic interventions on diurnal patterns of BP are warranted in African Americans with hypertension.

Resistant hypertension is more common in African Americans than in other racial groups80 and is associated with an increased risk of target organ damage81. Novel approaches for prevention and treatment of resistant hypertension in African Americans are needed.

In ALLHAT, once daily chlorthalidone (12.5 – 25 mg/d) for first-step drug therapy of hypertension was even more compelling for African Americans compared to Whites59. However, many clinicians are not prescribing chlorthalidone for treatment of hypertension, even in resistant hypertension82. Patients and clinicians may be concerned about the potential for side effects, including sexual dysfunction, and clinicians may need to be informed about the benefits of properly-dosed chlorthalidone and its well established tolerance and safety profile in large double-blinded clinical trials. Research is needed on ways to improve acceptance of properly dosed chlorthalidone for initial treatment of hypertension, particularly in African Americans. In SPRINT, more intensive BP treatment than is currently recommended resulted in similar health benefits in African Americans compared to all others68. In many African Americans with hypertension, the optimal approach to achieving the BP target used in SPRINT may be to initiate antihypertensive drug treatment with combination therapy rather than monotherapy. The International Society of Hypertension in Blacks (ISHIB) recommends a combination of CCB and RAS blocker as initial drug therapy in African Americans with stage 2 hypertension with use of a combination of a thiazide and RAS blocker only if there is volume overload3. This recommendation is based on evidence from a single RCT, Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH)83, with no separate results for the 1,416 African American participants. Also, the thiazide diuretic used in ACCOMPLISH (hydrochlorothiazide) was relatively short-acting, and its dosage was roughly equivalent to half that of the longer-acting thiazide-type diuretic (chlorthalidone) used in ALLHAT. The thiazide dosage employed in ACCOMPLISH was at most half that which has been shown to reduce CVD events in other trials. Therefore, identifying the optimal combination therapy in African Americans with hypertension remains an important unanswered research question.

Genetic determinants of the effects of antihypertensive therapy

Genetic studies in hypertension have largely focused on predictors of elevated BP levels. A logical next step is to extend genetic and pharmacogenetic studies to major CVD and renal outcomes. GenHAT, an ALLHAT genetics substudy, provides an opportunity to explore this question in a racially diverse population that includes about 15,000 African Americans with treated hypertension84. African Americans are substantially underrepresented in the datasets available for exploration of gene-treatment interactions. Fewer than 500 African American participants have been studied for Gene-Treatment interactions in GWAS studies85-87. This lack of data specific to African Americans has the potential to create a new disparity in the era of precision medicine. Partnerships with health care delivery sites that serve a high percentage of African Americans, such as Federally Qualified Health Centers, and with community-based organizations in predominantly African American communities could remedy this underrepresentation in genomic research. Datasets from RCTs with a substantial number of African Americans also represent a valuable resource for discovery of genome and exome sequencing variants that may predict beneficial and adverse effects of treatment in African Americans.

The pharmacogenomics of hypertension outcomes may benefit from adapting proof of concept studies conducted in other fields, where treatment effects have differed by race. One such approach is to use genetically defined African ancestry to study risk of hypertension-related disorders and its modification by antihypertensive treatment. In the field of nephrology, the pathogenesis of disease processes historically labeled “hypertensive nephrosclerosis” in African Americans has changed with discovery of the apolipoprotein L1 nephropathy gene (APOL1)88,89. Many non-diabetic African Americans with CKD, low level or absent proteinuria and hypertension have genetically mediated forms of primary glomerulosclerosis associated with variants in APOL190. In these patients, aggressive anti-hypertensive treatment with angiotensin converting enzyme inhibitors does not appreciably slow loss of kidney function91,92. Others, who present in a similar fashion have arteriolar nephrosclerosis on kidney biopsy90. There is controversy regarding the extent to which anti-hypertensive therapy alone slows progression of arteriolar nephrosclerosis-associated CKD. APOL1 variant genotyping of participants from ALLHAT and other studies with a large number of African Americans might be informative.

Individuals with recent African ancestry, such as African Americans, may inherit APOL1 G1 and G2 renal-risk-variants. Both variants are rare (or absent) in non-African populations; they appear to have been selected for protection against the parasite that causes African sleeping sickness (trypanosome brucei rhodesiense) in sub-Saharan Africa88,89. Approximately 40% of African Americans with ESRD may have APOL1-associated nephropathy and APOL1 renal-risk variants predict progression of CKD92,93. Additionally, these risk variants are associated with earlier failure of renal allografts that were transplanted from deceased African American compared to White donors94-96. However, in the Atherosclerosis Risk in Communities (ARIC) study, risk of CKD progression demonstrated substantial variability such that the majority of African Americans with and without APOL1 risk genotypes in the general population experienced similar rates of decline in glomerular filtration rate. Racial disparities in adverse health experience were pervasive in ARIC. Although APOL1 genotypes in ARIC were associated with a significant risk for adverse renal outcomes, they appeared to explain only a minority of these outcomes. In contrast to African Americans at high risk for CKD, these data do not support general African American population-based screening for APOL197. These findings suggest the need for additional studies, including:

1. Improved characterization of underlying kidney diseases within the framework of “hypertension-attributed” nephropathy in African Americans. Important goals would be to determine which non-diabetic African Americans with CKD, hypertension and low level proteinuria have APOL1-associated glomerulosclerosis and to better understand the value of APOL1 in risk prediction and treatment decisions. Clinical trials targeting novel therapeutic agents, including studies like ALLHAT that compare different classes of antihypertensive therapy, could then be tested for each disorder.
2. Identification of factors that modify the relationship between APOL1 and renal disease, including APOL1-second gene and APOL1-environmental interactions. Modifying factors may contribute to the multiplicity of renal histologic patterns in African Americans with kidney disease, and could prove useful in the selection of potential interventions.
3. Definition of the genetic basis for non-APOL1-mediated renal-limited disorders causing glomerulosclerosis, CKD, and secondary hypertension.
4. Conduct of genotyping studies embedded within large clinical services-based prospective series, such as the Patient Centered Outcomes Research Network (PCORNet) Clinical Data Research Networks (CDRNs) which have the capacity to screen, treat, characterize, follow and obtain biological specimens in large cohorts that include African American patients.

Intervention approaches and BP outcomes in quality improvement clinical trials

Over recent decades, there has been a large investment of public and non-public funds into improving the quality of hypertension care. A considerable amount of research has been focused on quality of hypertension care in African Americans, elimination of the race-related gap in blood pressure control and the higher rates of stroke and premature mortality noted in African Americans98. Much of this research, particularly that funded by the NHLBI, has focused on conduct of RCTs testing interventions that target patients, providers, clinics, health systems, or some combination of these groups99. Among these approaches, team-based interventions that assign healthcare responsibilities to a professional other than the patient’s primary care physician, such as a pharmacist or nurse, provide a potent and cost-effective strategy for improving BP control100-102. Team-based interventions seem to be as effective in African Americans as in others, but more scrutiny is needed, especially in the area of treatment optimization. There is also need to establish the optimal composition of hypertension care teams, the best strategies for interaction and communication, and the most efficient and cost-effective utilization of individual team members. Team-care delivered in non-traditional locations, including community pharmacies103, patient homes104, barber shops105, faith-based organization and workplaces, shows promise and is the subject of ongoing investigation. The cost-effectiveness and sustainability of these approaches need careful study.

Technology, including telemanagement, is another highly effective strategy, especially when combined with home BP monitoring and web-based management106,107. This approach has been less well studied in African Americans than in Whites.

Medication adherence in patients with hypertension and other chronic disorders is an important research area in quality improvement trials108-110, especially in African Americans108. Provider training in patient-centered communication skills is a promising strategy111,112. However, practitioners want better and more practical methods for detection and management of poor adherence, especially in patients with apparent treatment resistant hypertension. Further investigation of these methods is needed. In-person, telephone, and web-based motivational counseling all show promise113, but additional research is needed to identify the value of short-term counseling, including the durability of its effects on change in lifestyle and clinically meaningful outcomes.

With a rapidly evolving clinical practice environment, clinicians’ attitudes114 and uncertainty115 may be equally or more important compared to their level of knowledge. The quality of BP assessments for decision making in routine clinical practice also remains an important6,116-118 but poorly studied area, especially in small, clinical practice settings that predominantly serve African Americans. Available studies suggest clinic BP measurements may vary substantially from corresponding research readings119,120. Many contemporary trials, such as SPRINT, have devoted considerable effort to adherence with recommendations for accurate measurement of BP68. There is a need to understand the extent to which practitioners, including those caring for African American patients, adhere to recommendations for accurate BP measurement. Likewise, there is need to understand the barriers that limit adherence to BP measurement recommendations in clinical practice.

Recent comparative effectiveness quality improvement trials incorporate implementation research methods121-123. However, there is a need for greater attention to implementation and dissemination research124 on improving hypertension control in African Americans. Especially needed are studies of how specific activities and designed strategies affect the integration of evidence-based interventions into routine health care and community health practice. Likewise, there is need for study of the factors necessary for successful adoption and implementation of evidence-based interventions that have been successfully implemented in some sites and are ready for widespread use. Finally, barriers to hypertension control in African Americans exist at multiple levels including factors related to individual patients; family and social support systems; health care providers; organization and practice settings in which health care occurs; the local community environment; and local, state, and national health policy environments; but few studies to date intervene on more than two levels. More research studies should test interventions that target three or more levels - for example, interventions that link community, system and team-level approaches to individual provider- and patient-level programs of care.

Performance measures in clinical settings

Several performance measures have been developed to assist health care delivery systems and providers in their common goal to improve the quality of care for patients with hypertension. The National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS) measure is commonly used as a component of federal quality reporting programs. The current HEDIS measure for BP control utilizes the most recent ambulatory clinic BP reading for eligible individuals. If multiple readings are available, the lowest value can be selected. This approach results in substantial potential for ascertainment bias125, and fails to allow for differences in the difficulty of controlling hypertension based on patient characteristics.

In RCTs, substantial attention is paid to guideline recommendations for minimizing systematic error by standardizing the measurement procedures and minimizing random errors by averaging the readings68. In RCTs that target specified BP goals, not all patients in the intervention arm reach the goal BP. Research is needed to understand the impact of using the target BP’s from RCT as a performance metric. Such an approach has the potential to result in a higher proportion of patients meeting the BP target and lower clinic and out-of-office mean BPs compared to the experience in RCTs. Hence, it is unclear whether use of an RCT BP target as a performance metric is safe and beneficial126,127. 

Performance measures focused on achievement of a BP target as measured in clinic may have other unintended negative consequences, especially in African American populations. Providers who treat a disproportionately high number of patients with resistant hypertension, which is more common in African Americans128, may be unfairly penalized by use of current BP performance indicators. Similarly, there may be a disincentive for accurate reporting of BPs. Alternative measures, including change in BP over time, should be considered for patients with resistant hypertension. Reliance on clinic-based BP performance measures ignores the impact of nocturnal and masked hypertension, which are more common in African Americans, and may contribute to overall disparities in cardiovascular disease129. Incorporation of home BP readings into performance measures requires technological advances to validate and systematically include these data in electronic medical records, so they can be a useful resource for clinicians. Finally, an emerging contributor to disparities is the increasing burden of hypertension in adolescents. African American adolescents have markedly higher rates of uncontrolled BP compared to their White counterparts130,131.

Performance measure-based quality improvement initiatives have the potential to close racial and ethnic gaps in BP control. However, substantial gaps remain in collection of race and ethnicity data, and few governmental organizations or health systems currently report data on racial/ethnic disparities in BP control. The quality of race/ethnicity data collected by health systems should be improved and standardized to allow public reporting and monitoring of racial/ethnic disparities in BP control.

Building the Workforce Capacity

Existing models suggest that increasing workforce diversity by training investigators who are members of under-represented minorities is an important element in reducing health disparities, but little is known about diversity of the workforce committed to hypertension disparities research. Most training programs are focused on academic scholarship and mentorship.  Typically, programs devote insufficient attention to the technical skills needed to address racial disparities by measurement of the social determinants associated with hypertension; application of health services research methods to explore the burden and mechanisms of racial disparities; or selection of clinical outcomes in event-based RCTs and BP outcomes in quality improvement trials that are especially relevant in studies of African Americans.

Improving BP control in African Americans is likely to require multilevel strategies that go beyond traditional biomedical approaches but also address social and environmental factors. This highlights the need for novel interdisciplinary training programs that incorporate the social and behavioral sciences, environmental factors and policy more broadly. Existing programs, particularly training cores within larger programs, need to be evaluated for their success in developing early stage investigators committed to hypertension disparities research. Incorporation of workgroups designed to facilitate training related to hypertension in African Americans should be explored in large ongoing multisite observational studies such as the Coronary Artery Risk Development in Young Adults (CARDIA)132, and the Multi-Ethnic Study of Atherosclerosis (MESA)133 and in large multicenter hypertension treatment RCTs such as the SPRINT68,134. Use of databases from completed RCTs such as the ALLHAT59,135,136, with continued passive participant follow-up, and the Action to Control Cardiovascular Risk in Diabetes (ACCORD)137,138 also provides a rich opportunity for mentored learning and exploration of important issues related to high BP in African Americans. Hypertension training programs need to bridge instruction related to etiology and translation of research findings to application in clinical practice and formulation of health policy.

Further, they need to focus on developing multi-sectorial partnerships that intervene at the environmental, housing, educational and behavioral levels, including the built environment and access to better quality and affordable foods that are low in sodium and saturated fat. There is a need for NIH workshops that target specific areas of scientific inquiry within the topic of disparities in hypertension - similar to the Office of Behavioral and Social Sciences (OBSSR) Summer Institute on RCTs139. Programs should foster development of professional networks for trainees and young investigators through sponsoring networking meetings and cross-institutional training while recognizing the importance of local and national role models in the early stages of career development. Given the importance of clinical practice to dissemination and implementation of research results, training programs should include practicing clinicians who show interest in research but do not plan to make it the main focus of their career.

Recommendations

Surveillance, assessment and causes of high BP

• There is a need for surveys that are more relevant to day-to-day clinical practice settings, including clinical practices that predominantly serve African Americans. An important focus should be to determine the adequacy of BP measurements and their use in diagnosis and management of hypertension.
• There is a need for additional study of environmental, psychosocial and behavioral factors (social determinants) that can prevent hypertension and improve BP control.
• Strategies to improve identification and management of masked hypertension in African Americans should be developed.
• The physiologic factors that contribute to altered diurnal variation and visit-to-visit variability of BP should be studied.

Lifestyle change and other nonpharmacological interventions

• Population-based studies that promote adherence to lifestyle and other non-pharmacological interventions and antihypertensive drug therapy are warranted, especially studies that explore the use of mobile and technology-based solutions. This is an area for potential collaboration with the OBSSR in the broader context of improving health in African Americans across their lifespan.
• A broad portfolio of research, including mechanistic studies and clinical trials, to test the main and interactive effects of increasing potassium intake and reducing sodium intake is warranted in African Americans. For potassium, there are several unresolved issues, including dose response relationship, long-term beneficial effects, safety, and the role of non-chloride anions.
• Given the increasing recognition that antecedents of hypertension in adults begin early in life, the efficacy and effectiveness of lifestyle and other non-pharmacological interventions to prevent and delay the onset of hypertension in African American children should be a high priority.

Treatment and adherence

• The ALLHAT findings suggest chlorthalidone is the preferred agent for first-step antihypertensive drug therapy in most adults, especially in African Americans, but chlorthalidone is used infrequently in practice. Clinician and patient barriers to use of chlorthalidone and other recommended antihypertensive treatments should be explored. Understanding the mechanism of the clinical effects of chlorthalidone, especially in African Americans, could facilitate greater use of this agent in clinical practice.
• Additional study of albuminuria as an effect modifier during BP-lowering and pharmacotherapy in African Americans with hypertension and CKD is warranted.
• Trials comparing different combination therapies in African Americans are needed to optimize long term clinical outcomes, improve adherence, and prevent or delay the onset of treatment resistant hypertension.
• Trials should be conducted to determine whether treatment strategies targeting reduction in visit-to-visit BP variability or nocturnal hypertension can reduce the CVD risks associated with these conditions in African Americans.
• Strategies to enhance management and improve outcomes in African Americans with resistant hypertension should be developed and tested, including targeting of barriers to treatment adherence with nonpharmacological and drug interventions.

Genetics, genomics and pharmacogenetics

• There is need for additional pharmacogenomic studies in patients with hypertension, especially in African Americans, including utilization of ALLHAT and GenHAT resources.
• Whole genome (and exome) sequencing are now affordable and practical for use in RCTs. Consideration of African ancestry may be a useful approach to study modification of response to antihypertensive treatment on CVD outcomes.
• Further study of APOL1 variants may improve our understanding of the relationship between CKD and hypertension, and whether affected patients require alternative treatment approaches.

Quality improvement

• There is a need to study strategies for implementation of successful hypertension quality improvement interventions in clinical practice settings (including patient, provider, clinic/system, team, and multilevel approaches), and to assess performance measures that are intended to meet the needs of organizations and providers who care for a diverse range of patients, including those with practices that have a high percentage of African Americans.
• Scaling up best practices and trial-tested effective interventions will require interactions with a broad constituency that includes regulatory authorities, patient advocacy groups, and multi-sectorial partnerships outside of the health care delivery system. Evaluation using RCT designs, the current gold standard, may not be feasible. Whatever the study design, such evaluations need to include detailed investigation of factors influencing successful implementation as well as rigorous assessment of short- and long-term individual- and population-level beneficial and adverse effects.
• Performance measures that facilitate achievement of quality improvement goals in patient care settings with a high proportion of African American patients should be developed.

Building the workforce capacity

• In addition to research studies, there is a need for training programs that cover the full spectrum of hypertension, from etiology to clinical and public health practice. They should underscore proficiency in technical skills, such as BP measurement issues, and how to investigate and address racial disparities in hypertension. Training program teams should be interdisciplinary with inclusion of social scientists, policy makers and clinicians who do not plan to make research the focus of their careers. They should emphasize the value of multi-sectorial models for enhancing care. Fostering networking for trainees and junior investigators is also warranted. Existing programs have the potential to accommodate many of these requirements. New initiatives, such as focused scientific workshops, should be developed to specifically concentrate on hypertension in African Americans, addressing both the health disparities and clinical needs of this population.

Disclosure

The views expressed in this executive summary are those of the authors and do not necessarily represent the American Medical Association; National Institutes of Health; or the US Department of Health and Human Services.

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Roster

Chair: Paul K. Whelton, M.B., M.D., M.Sc.
Show Chwan Professor of Global Public Health
Department of Epidemiology
Tulane University School of Public Health and Tropical Medicine

Lawrence J. Appel, M.D., M.P.H.
C. David Molina, M.D., M.P.H. Professor of Medicine, Epidemiology and International Health
Director, Welch Center for Prevention, Epidemiology, and Clinical Research
Johns Hopkins Medical Institutions

Jamy D. Ard, M.D.
Associate Professor
Department of Epidemiology & Prevention
Department of Internal Medicine
Wake Forest School of Medicine

Donna K. Arnett, Ph.D., M.S.P.H.
Professor and Chair
Department of Epidemiology
Associate Dean for Academic and Strategic Programs
School of Public Health
University of Alabama at Birmingham

Barry L. Carter, Pharm.D.
The Patrick E. Keefe Professor in Pharmacy
College of Pharmacy
Professor, Department of Family Medicine
Roy J. and Lucille A. Carver College of Medicine
University of Iowa

Lisa A. Cooper*, M.D., M.P.H.
James F. Fries Professor of Medicine
Division of General Internal Medicine
Director, Johns Hopkins Center to Eliminate Cardiovascular Health Disparities
Johns Hopkins University School of Medicine

Richard Cooper, M.D.
Professor and Chair, Public Health Sciences
Loyola University Medical School

William C. Cushman*, M.D.
Chief, Preventive Medicine
Veterans Affairs Medical Center
Professor, Preventive Medicine, Medicine, and Physiology
University of Tennessee Health Science Center

Barry R. Davis, M.D., Ph.D.
Guy S. Parcel Chair in Public Health
Professor of Biostatistics
Director, Coordinating Center for Clinical Trials
The University of Texas School of Public Health

Ana V. Diez Roux*, M.D., Ph.D., M.P.H.
Dean and Distinguished Professor of Epidemiology
Dornsife School of Public Health
Drexel University

Keith C. Ferdinand*, M.D.
Professor of Clinical Medicine
Tulane University School of Medicine

Barry I. Freedman, M.D.
John H. Felts III Professor of Internal Medicine
Chief, Section on Nephrology
Wake Forest School of Medicine

Alan Go, M.D.
Chief, Cardiovascular and Metabolic Conditions Section
Director, Comprehensive Clinical Research Unit
Regional Medical Director for Clinical Trials
Kaiser Permanente Northern California Division of Research

David Hyman, M.D., M.P.H.
Professor of Medicine and Family & Community Medicine
Chief, Section of General Internal Medicine
Baylor College of Medicine

Karen Margolis, M.D., M.P.H.
Senior Medical Director - Research
HealthPartners Institute for Education and Research

Katherine Mills, Ph.D.
Postdoctoral Fellow
Johns Hopkins University and Tulane University

Edgar (Pete) R Miller III Ph.D., M.D.
Professor of Medicine
Johns Hopkins University

Paul Muntner*, Ph.D.
Professor and Vice Chair
Department of Epidemiology
University of Alabama at Birmingham

Ann Marie Navar, M.D., Ph.D.
Fellow
Cardiovascular Disease
Duke University School of Medicine

Gbenga Ogedegbe, M.D., M.S., M.P.H.
Professor of Population Health and Medicine
Chief, Division of Health & Behavior
Director, Center for Healthful Behavior Change
Vice Dean and Chief Medical Officer, Global Institute of Public Health
New York University School of Medicine

Mahboob Rahman, M.D.
Professor of Medicine
Case Western Reserve University
University Hospitals Case Medical Center
Louis Stokes Cleveland VA Medical Center

Michael Rakotz, M.D.
Director, Chronic Disease Prevention
Improving Health Outcomes
American Medical Association

Herman Taylor*, M.D.
Endowed Professor and Director
Cardiovascular Research Institute at Morehouse School of Medicine

George Thomas, M.D., M.P.H.
Nephrology and Hypertension
Glickman Urological and Kidney Institute
Cleveland Clinic

Jonathan Tobin, Ph.D.
President/CEO
Clinical Directors Network, Inc.
Professor, Department of Epidemiology & Population Health
Albert Einstein College of Medicine of Yeshiva University

Jackson T Wright Jr*, M.D., Ph.D.
Professor of Medicine
Program Director
William T Dahms MD Clinical Research Unit
Clinical and Translational Science Collaborative
Director Clinical Hypertension Program
Case Western Reserve University

Sung Sug (Sarah) Yoon R.N., Ph.D.
Clinical Epidemiologist
National Health and Nutrition Examination Survey
National Center for Health Statistics
Centers for Disease Control and Prevention (CDC)

NIH Participants:

Kevin Abbott, M.D., M.P.H.
Program Director
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lawrence Agodoa*, M.D.
Director
Office of Minority Health Research Coordination
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Jeffrey A. Cutler*, M.D., M.P.H
Consultant
Clinical Applications and Prevention Branch
Division of Cardiovascular Diseases (DCVS)
National Heart, Lung, Blood Institute (NHLBI)

Patrice Desvigne-Nickens*, M.D.
Medical Officer
Heart Failure and Arrhythmias Branch
Division of Cardiovascular Sciences (DCVS)
National Heart, Lung, and Blood Institute (NHLBI)

Paula T. Einhorn*, M.D., M.S.
Medical Officer/Program Director
Clinical Applications and Prevention Branch
Division of Cardiovascular Sciences (DCVS)
National Heart, Lung, and Blood Institute (NHLBI)

Michael M Engelgau, M.D., M.S.
Deputy Director
Center for Translation Research and Implementation Science (CTRIS)
National Heart Lung and Blood Institute (NHLBI)

Lawrence J. Fine M.D., Dr. PH
Branch Chief
Clinical Applications and Prevention Branch
Division of Cardiovascular Sciences (DCVS)
National Heart, Lung, and Blood Institute (NHLBI)

Nara Gavini, PhD., MPhil.
Center for Translation Research
and Implementation Science (CTRIS)
National Heart, Lung, and Blood Institute (NHLBI)

Paul L. Kimmel, M.D., MACP
Senior Advisor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

George A. Mensah, M.D.
Director, Center for Translation Research
and Implementation Science (CTRIS)
Acting Director, Division of Cardiovascular Diseases (DCVS)
National Heart Lung and Blood Institute (NHLBI)

Marva Moxey-Mims, M.D.
Deputy Director for Clinical Research
Division of Kidney, Urologic, and Hematologic Diseases
Director, Pediatric Nephrology and Renal Centers Programs
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Andrew S. Narva, M.D.
Director, National Kidney Disease Education Program 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Charlotte A. Pratt, Ph.D., M.S., R.D.
Program Director
Clinical Applications and Prevention Branch
Division of Cardiovascular Sciences (DCVS)
National Heart, Lung, and Blood Institute (NHLBI)

Michael Wolz
Statistician
Epidemiology Branch
Division of Cardiovascular Sciences (DCVS)
National Heart, Lung, and Blood Institute (NHLBI)

*Member of Planning Committee