Hypertension in African Americans: Unanswered Questions and Future Directions for the Jackson Heart Study

Introduction

This report resulted from a working group assembled by the Jackson Heart Study (JHS) coordinating center as part of a symposium to identify, discuss and refine key questions, related to hypertension in African-Americans, that can be addressed in the National Heart, Lung and Blood Institute (NHLBI)-sponsored study. The symposium and working group were assembled to assist in the preparation for the next phase of the JHS. The JHS is a longitudinal observational study designed to identify cardiovascular disease (CVD) risk factors among African Americans and to develop the infrastructure for training the next generation of health disparities researchers.¹ Between 2000 and 2004, 5,306 community-dwelling African Americans, aged ≥21 years, were enrolled from the tri-county area of Jackson, MS. In addition to a baseline study visit, follow-up visits were conducted in 2005–2008 and 2009–2013. JHS participants are contacted annually by telephone to identify potential CVD events that are adjudicated by trained clinicians.²

Hypertension is more common in African Americans than any other race/ethnic group in the US.³ Additionally, African Americans have a higher incidence of hypertension-related CVD and end-stage renal disease than other race/ethnic groups in the US.^{4, 5} The hypertension working group thought broadly about essential research questions related to hypertension in African Americans. We considered research questions that could be addressed through continued observational follow-up of the JHS cohort or by conducting interventions among JHS participants.

The working group benefited from reviewing the NHLBI Strategic Vision and a recently published report from an NHLBI working group addressing research needs to improve hypertension treatment and control in African Americans.^{6, 7} Also, this report builds on the published work in the area of hypertension from the JHS (Table 1). Some of the suggestions from the working group require new study visits and are purely observational, while others involve interventions in JHS participants and the Jackson, MS community. Several questions considered by the working group are unique to African Americans while others address unanswered questions impacting all race/ethnicity groups that can be efficiently conducted using the JHS infrastructure and that may benefit from the extensive phenotyping and genotyping that has already been performed on study participants.^{8, 9}

Table 1.

Hypertension-related scientific publications from the Jackson Heart Study, 2008–2016.

First author, publication year	PubMed ID	Title
Wyatt SB 2008	18268140	Prevalence, awareness, treatment, and control of hypertension in the Jackson Heart Study.
Hickson DA 2011	21654853	Socioeconomic position is positively associated with blood pressure dipping among African-American adults: the Jackson Heart Study.
Ehret GB 2011	21909115	Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
Sims M 2012	22401510	Perceived discrimination and hypertension among african americans in the Jackson Heart Study.
Harman J 2013	23730984	Treatment of hypertension among african americans: The Jackson Heart Study.
Subramanyam MA 2013	23906131	Socioeconomic status, John Henryism and blood pressure among African-Americans in the Jackson Heart Study.
Fox ER 2013	23184379	Association of plasma B-type natriuretic peptide concentrations with longitudinal blood pressure tracking in African Americans: findings from the Jackson Heart Study.
Ogedegbe G 2013	23676475	Correlates of isolated nocturnal hypertension and target organ damage in a population-based cohort of African Americans: the Jackson Heart Study.
Tanner RM 2015	26099630	Association between 24-hour blood pressure variability and chronic kidney disease: A cross-sectional analysis of african americans participating in the Jackson Heart Study.
Diaz KM 2015	25499058	Prevalence, determinants, and clinical significance of masked hypertension in a population-based sample of african americans: The Jackson Heart Study.
Davis SK 2015	25885320	Association of adiponectin with type 2 diabetes and hypertension in African American men and women: the Jackson Heart Study.
McMullan 2015	26066645	Prospective analysis of the association of ambulatory blood pressure characteristics with incident chronic kidney disease.
Booth JN 2016	27354424	Masked hypertension and cardiovascular disease events in a prospective cohort of blacks: The Jackson Heart Study.
Abdalla M 2016	27339075	Hypertension and alterations in left ventricular structure and geometry in african americans: The Jackson Heart Study.
Abdalla M 2016	27185746	Masked hypertension and incident clinic hypertension among blacks in the Jackson Heart Study.
Bromfield SG 2016	27169827	Ambulatory blood pressure monitoring phenotypes among individuals with and without diabetes taking antihypertensive medication: The Jackson Heart Study.
Redmond N 2016	27025968	Prevalence of masked hypertension and its association with subclinical cardiovascular disease in african americans: Results from the Jackson Heart Study.
Booth JN III 2016	26754344	The association of reduced lung function with blood pressure variability in african americans: Data from the Jackson Heart Study.
Tanner RM 2016	26279070	White-coat effect among older adults: Data from the Jackson Heart Study.
Bromfield SG 2016	27777359	Cardiovascular risk factors and masked hypertension: The Jackson Heart Study.
Ford CD 2016	26964661	Psychosocial factors are associated with blood presure progression among African Americans in the Jackson Heart Sudy
Spruill TM 2016	26869251	Psychosocial correlates of nocturnal blood pressure dipping in African Americans: The Jackson Heart Study

For a full list of Jackson Heart Study manuscripts is available: https://www.jacksonheartstudy.org/Research/Publications/Publications-List

Study Design Considerations

A long-standing issue in the performance of longitudinal observational studies has been whether nested intervention studies would adversely impact the quality of the observational data being collected. In recent years, NHLBI has been advised to consider nesting interventions within their large cohort studies.¹⁰ A few randomized controlled trials have been nested within NHLBI cohorts including the Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA).^{11, 12} Nesting interventions in longitudinal observational studies can leverage the existing data collection infrastructure, enhance recruitment yields through enrollment of individuals engaged in medical research, reduce costs, and provide better knowledge on the generalizability of study results, given the detailed phenotyping and genotyping that has been performed. However, there are challenges with nesting interventions within an established cohort. Interventions may affect future findings on risk factor and disease incidence and risk factor-outcome associations if observational follow-up is ongoing. Also, there are few data on the potential effect of nested interventions on participant retention in the parent cohort study.

It has been well-recognized that health issues identified through observational studies need to receive proper medical attention. Contemporary observational studies adhere to ethics guidelines that include provisions for follow-up to health concerns identified in participants. In the JHS, all participants identified as having hypertension during the study examinations were referred to physicians to confirm this diagnosis and provide treatment. For participants without a healthcare provider, the JHS staff members worked with them to identify one. Nesting randomized trials, comparing new hypertension therapies to standard care, in JHS would take advantage of this process and could provide an opportunity to test interventions in a rigorous, organized fashion, while allowing for better tracking of treatments received in a cohort study after the standard exam visit.

Another consideration is whether to expand data collection beyond the initially enrolled JHS cohort to make observations and conduct interventions that include the broader community of Jackson, MS. This approach can test hypotheses that cannot be addressed only utilizing the currently enrolled JHS participants and may allow for broader generalizability. An additional opportunity would involve the enrollment of participants’ offspring. This may be particularly useful for familial aggregation studies of genetic and environmental factors.

Measurement of Blood Pressure and Cardiovascular Parameters

Blood pressure is measured in almost all outpatient primary care clinic visits. However, there are still many unanswered questions regarding the appropriate technique to measure blood pressure accurately and reliably.

Office blood pressure measurement

Since the inception of the JHS, several changes in blood pressure measurement technology have occurred, including discontinuation of mercury sphygmomanometry in clinical practice and research studies. At the first JHS exam, random zero mercury manometers were used. For the second and third exams, a semi-automated sphygmomanometer was used. While blood pressure has been calibrated across the three JHS exams, there is uncertainty about how blood pressure should be measured in future research studies and clinical practice.¹³ The recently completed Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated substantial reductions in CVD and all-cause mortality with a target goal for systolic blood pressure < 120 mm Hg versus < 140 mm Hg.¹⁴ During follow-up, some SPRINT participants had their blood pressure measured using an automated sphygmomanometer without a technician in the room. The applicability to clinical practice of the systolic blood pressure target goal of 120 mm Hg has been questioned because few patients have their blood pressure measured while alone in the clinic using an automated sphygmomanometer.¹⁵ Discrepancies between blood pressure measurements taken using an automated sphygmomanometer, with and without an observer present, can be assessed in the JHS cohort and these analyses can be used to inform current and future hypertension management guidelines. Prior blood pressure measurements can be calibrated to the automated measurements which will allow investigation of cumulative blood pressure burden in African Americans.

Out-of-office blood pressure assessment

The JHS conducted ambulatory blood pressure monitoring (ABPM) at baseline among 1,148 participants, making it one of the largest population-based studies with ABPM among African Americans. Among JHS participants with blood pressure in the hypertensive range (i.e., typically systolic/diastolic blood pressure ≥ 140/90 mm Hg) when measured in the office setting, approximately 30% had white coat hypertension, defined by blood pressure not in the hypertensive range (i.e., typically systolic/diastolic blood pressure < 135/85 mm Hg) when measured outside of the of the office.¹⁶ Prior studies suggest that white coat hypertension may not be associated with increased CVD risk.¹⁷ However, these studies have been conducted mostly in Asian and European populations, and there are few data on out-of-office blood pressure assessment in community-dwelling African Americans.

In contrast to white coat hypertension, several blood pressure phenotypes including masked hypertension, nocturnal hypertension and non-dipping blood pressure have been associated with increased CVD risk.^{18, 19} The prevalence of nocturnal hypertension is substantially higher in African Americans compared with other race and ethnic groups.^{20, 21} The usual blood pressure dip during sleep does not occur in many African Americans.^{20, 21} Masked hypertension, defined by blood pressure in the hypertensive range outside of the office setting with non-hypertensive blood pressure when assessed in the office setting, is common among African-Americans, especially those with chronic kidney disease and may result in the under-treatment of a high-risk population.^{22, 23} In JHS, we estimated a prevalence of masked hypertension of 34% when using daytime blood pressure from ABPM and 52% when considering daytime, nighttime or 24-hour blood pressure.^{22, 23} Observational studies could be used to identify risk factors for, and outcomes related to, masked hypertension, nocturnal hypertension and non-dipping blood pressure. With repeated ABPM assessments, JHS can identify factors associated with incident hypertension phenotypes. Additionally, few studies have included both ABPM and home blood pressure monitoring (HBPM).²⁴ By conducting both ABPM and HBPM in future exams, the JHS could provide evidence on the strengths and weaknesses of different approaches for reliable out-of-office blood pressure assessment.

Importantly, randomized trials are needed to determine whether treating nocturnal hypertension, non-dipping blood pressure and masked hypertension reduce CVD risk. Night-time dosing of antihypertensive medication reduced the occurrence of CVD events in a trial conducted in Spain.²⁵ However, no benefit of nighttime dosing of antihypertensive medication on night-time or daytime blood pressure was present in a randomized trial of African Americans with established chronic kidney disease.²⁶ Randomized trials are needed to identify pharmacologic and lifestyle approaches that can reduce CVD risk among adults with masked hypertension.

The circadian clock is comprised of a central component, which is in the suprachiasmatic nucleus of the brain, and peripheral components, located throughout the rest of the body including the kidneys, liver, and vasculature.²⁷ Four major circadian genes have been identified: CLOCK, BMAL1, Period (per), and Cryptochrome (Cry).^{27, 28} Given the extensive genotyping of the JHS cohort, including whole genome sequencing, investigating whether these genes contribute to non-dipping blood pressure and nocturnal hypertension could be conducted.

An enhanced vascular laboratory in the JHS

African Americans have a higher prevalence of end-organ damage attributed to elevated blood pressure than the general population.²⁹ It is unclear if vascular function provides prognostic value beyond conventional blood pressure measures and whether vascular function measurements could inform the management of hypertension or be used as treatment targets. In addition to ABPM and HBPM, measures that can be performed in JHS include pulse wave analysis to assess pulse wave velocity, augmentation index, and central aortic pressure, echocardiogram to assess systolic and diastolic function, and ankle brachial index to assess peripheral arterial disease. Each of these measures can be obtained non-invasively and they can provide insight into the mechanisms underlying the association of elevated blood pressure and CVD risk.

Lifestyle and Environmental Issues

Racial differences in lifestyle and environmental exposures that can result in increased risk for hypertension and hypertension-related CVD are well-described.³⁰ However, much remains to be learned, especially with respect to mechanisms relating lifestyle and environment exposures to blood pressure and interventions that can be sustained to improve lifestyle and remove environmental exposures over long periods of time. Primordial prevention is important because antihypertensive medication does not reduce CVD risk to the level experienced by those who never develop hypertension.³¹ Also, the JHS has extensive geocoded information that can be used to investigate potential effects of neighborhood and environmental factors on the longitudinal course of the different hypertension phenotypes.

Dietary intake

Limited work has been done to understand the contribution of dietary patterns to hypertension among African Americans. While certain healthy dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) pattern, lead to improved blood pressure control, there is increasing concern that the diet consumed in much of the south is unhealthy and has adverse effects on cardiovascular health.^{32, 33} The baseline JHS interview included a food frequency questionnaire (FFQ) that was specifically designed for the Southern US population.^{34, 35} This FFQ was validated in a subset of JHS participants.³⁶ A single measure of dietary intake may not be truly representative of the dietary exposure that JHS participants have experienced since baseline. Re-administering the FFQ can be used to categorize participants who have versus have not made specific changes in intake of nutrients and dietary patterns, allow contemporaneous analysis of current associations and, when combined with the baseline data, provide a more accurate estimate of long term exposure to dietary factors and their impact on hypertension risk and blood pressure control.

Sodium and potassium intake

One of the most striking differences between African-Americans and non-African-Americans are in the effects of electrolyte intake on blood pressure. Specifically, African-Americans have a greater blood pressure response to reduced sodium and increased potassium intake.^{37, 38} JHS is uniquely positioned to address mechanistic, clinical, and population-based research related to sodium and potassium intake. For example, few studies have accurate measurements of sodium and potassium intake as this would require collecting multiple 24-hour urine samples.³⁹ JHS successfully collected a single 24-hour urine sample at baseline and could obtain subsequent collections at future study visits to conduct better contemporaneous assessments of sodium and potassium intake. Intervention trials could address the response of potassium supplementation on various outcomes, including nocturnal blood pressure, arterial stiffness and other subclinical outcomes (e.g., albuminuria).

Research on the timing of salt intake is warranted, given preliminary evidence that ingestion of a high salt meal just prior to sleep may lead to an altered circadian pattern of urinary salt excretion and an altered diurnal pattern of blood pressure.⁴⁰ Two studies have reported a higher nighttime/daytime ratio of urinary sodium excretion to be associated with higher nighttime blood pressure and reduced blood pressure dipping.^{41, 42} Observational (e.g., assessing time of sodium excretion) and intervention (e.g., experimentally changing the time of day when sodium is consumed) studies may provide insights into the role of sodium intake and time of consumption on the diurnal pattern of blood pressure. Other research could focus on the level of kidney function at which potassium transitions from beneficial to harmful, a critically important issue in chronic kidney disease management. Given the strong basic research infrastructure in Jackson MS, translational work investigating physiological pathways through which sodium and potassium intake affect blood pressure could be conducted in the JHS.

Physical activity

African Americans engage in less physical activity than non-Hispanic whites.⁴³ Studies that better quantify physical activity, both in terms of type (e.g., active living or intended exercise) and place (e.g., work or leisure time), and hypertension risk are needed. Most studies of physical activity have relied on participant self-report. Actigraphy could be collected in future JHS visits to provide an objective measure of activity. Also, sitting time/sedentary behaviors have been associated with higher blood pressure and this association could be further evaluated using actigraphy.⁴⁴ Randomized trials have demonstrated that physical activity lowers blood pressure, but few of these studies have included African Americans.⁴⁵ Trials focused on increasing activity levels can be nested within the JHS with the explicit goal of lowering blood pressure and identifying pathways through which activity reduces blood pressure (e.g., weight loss, stress reduction, improvements in vascular function).

Sleep

More fragmented sleep, greater time spent in light sleep (stage 1), less time spent in rapid-eye movement sleep, and more arousals from sleep have been associated with an increased risk for hypertension and reduced blood pressure dipping.⁴⁶ Sleep apnea has also been associated with reduced blood pressure dipping.⁴⁷ The extent to which sleep disturbances contribute to an altered diurnal blood pressure pattern in African Americans and whether improving sleep hygiene restores a normal diurnal blood pressure pattern could be examined in the JHS. Information on actigraphy and polysomnography has been obtained for a subset of JHS participants in a recently completed ancillary study. Analyzing the association of sleep problems with uncontrolled blood pressure, treatment resistant hypertension and abnormal diurnal blood pressure patterns could provide useful information on potential approaches for improving blood pressure control.

Psychosocial factors

African Americans are disproportionately exposed to chronic stressors including low socioeconomic status, discrimination and relationship stress compared with non-Hispanic whites, which contributes to health disparities.⁴⁸ Intervening on stress-related behavioral and pathophysiological processes may reduce hypertension risk.⁴⁹ Additional relevant constructs (e.g., rumination) and biomarkers of stress could be measured at a future JHS visit to enhance the understanding of mechanisms and provide insights into novel intervention targets. Also, the study of resilience and other psychosocial factors (e.g., mindfulness) that promote successful adaptation to adversity may inform primary prevention strategies for hypertension. Although exposure to stressful events and circumstances cannot always be reduced, perceived stress and associated psychological risk factors (e.g., depression, anxiety) can be modified through psychosocial interventions.⁵⁰ Those in greatest need may be least likely to participate in such programs due to limited access (e.g., cost, convenience) or lack of cultural or individual tailoring. Working with JHS participants, highly tailored interventions can be developed focusing on hard-to-reach groups. Adding ecological momentary assessments and mobile sensors at a future JHS visit would inform the development of just-in-time adaptive interventions to reduce the experience and consequences of stress.

Environmental exposures

Several environmental toxins have been associated with hypertension.^51–53 Although blood lead concentrations have declined markedly since lead addition to gasoline and paint were halted in the 1970s, they remain many orders of magnitude higher than in the pre-industrial era and associated with the prevalence of hypertension.⁵¹ Blood lead concentrations are higher in African Americans compared with non-Hispanic whites in the US and exposure is likely to continue as many people live in old housing with lead-based paint and ingest contaminated water supplies, as recently witnessed in Flint, Michigan.⁵¹ In the JHS, recent lead exposure can be measured using whole blood while long-term (30+ years) lead exposure can be assessed using x-ray fluorescence.⁵⁴ Additional environmental exposures, including perfluroalkyl chemicals, cadmium, and arsenic and hypertension risk could be investigated in the JHS.

Pharmacological Studies

Antihypertensive medication adherence

Poor antihypertensive medication adherence accounts for a substantial percentage of uncontrolled blood pressure among adults with hypertension.⁵⁵ Prior studies suggest African Americans have lower adherence to antihypertensive medication compared with other race/ethnic groups in the US.^{56, 57} Most previous epidemiologic studies, including the JHS, have used self-report to assess medication adherence. While this approach has provided some insight into factors associated with low adherence, it is susceptible to recall and social desirability bias. Recent studies have used mass spectrometry to measure urine metabolites of antihypertensive medication.⁵⁸ Also, administrative claims data from commercial insurers or Medicare Part D have been used to provide objective data on medication adherence.⁵⁶ Given the high percentage of participants with hypertension, the JHS is positioned to test interventions to improve antihypertensive medication adherence. Interventions to improve adherence that can be tested in the JHS include those directed at unintentional (e.g., forgetfulness) and intentional (e.g., beliefs about medications) behaviors.

Trials of drug classes

Clinical trials have demonstrated the effectiveness of chlorthalidone in reducing blood pressure and cardiovascular events.⁵⁹ However, the vast majority of US adults, including African Americans, with hypertension take hydrochlorothiazide rather than chlorthalidone.⁶⁰ There are theoretical reasons to believe that chlorthalidone may be superior to hydrochlorothiazide in African Americans including its longer half-life.⁶¹ A randomized trial comparing chlorthalidone to hydrochlorothiazide among African Americans can be done in JHS to assess whether this would result in the need for fewer classes of antihypertensive medication to achieve blood pressure control and prevent CVD events.

Pharmacogenetic trials

The JHS provides an opportunity to identify the role of genetics on hypertension and hypertension-related CVD and renal disease among African Americans, given that extensive genotyping of participants has already occurred. Of particular interest are APOL1 risk variants (G1 and G2), which are common among African Americans and associated with an increased risk for end-stage renal disease and renal disease progression.⁶² Fewer data have been published on the association between APOL1 risk variants and hypertension and blood pressure control. Also, randomized trials on the effectiveness of different drug classes for improving blood pressure control and reducing CVD events in African Americans with APOL1 risk variants can be evaluated in the JHS. West-African ancestry may provide important information to guide antihypertensive class selection. A smaller blood pressure reduction with ACE-inhibitors has consistently been observed for African Americans compared with non-Hispanic whites.⁶³ Also, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, chlorthalidone reduced the risk for heart failure and stroke when compared with lisinopril among African Americans while there was no difference among whites.⁶⁴ African Americans are genetically heterogeneous ranging from 30% to 99% West African Ancestry.⁶⁵

Variation in response to antihypertensive medication by West African ancestry can be evaluated in a trial nested within the JHS.

Treatment and Control Issues

System approaches

Compelling evidence for achieving high blood pressure control rates in African Americans has been demonstrated in clinical trials and routine clinical practice.^66–68 In the Kaiser Permanente Southern California health system, hypertension control has been achieved in more than 80% of African Americans and racial and ethnic disparities in hypertension control have been eliminated.^{67, 68} Strategies for a successful hypertension control program include expanded healthcare access, established clear roles and responsibilities of care providers, and physician-led education that emphasizes the importance of guideline adherence and treatment intensification, as needed.

A successful blood pressure control model can be created in Jackson, Mississippi; however, it will require adoption of systemic implementation strategies proven effective in other health care settings and their adaptation to suit the local Jackson socioeconomic, environmental, and cultural context.⁶⁹ An example of a successful program implemented in the Southeastern US, the Hypertension Initiative, has resulted in improved blood pressure control in a practice-based network of clinics in South Carolina.⁷⁰ Lessons from the Hypertension Initiative could be adapted for use in Mississippi. Given its established infrastructure, the JHS is positioned to test the feasibility of implementing a blood pressure control program. Initial steps could include the development of a community-wide patient registry and a learning healthcare system that would allow interventions to be rigorously evaluated.

Population-level interventions

Over the past 30 years, several community-based outreach programs focusing on the prevention, awareness, treatment and control of hypertension have been implemented within African-American communities.⁷¹ Many of these programs have been based in churches and barbershops/beauty salons^{71, 72} or have engaged community health workers and allied health professionals, such as nurse practitioners. While these programs have been effective, few data are available on the implementation of these programs in the South. The feasibility and long-term sustainability of these community-based outreach programs, some of which require intense resources is unclear.⁷³ The inclusion of technology-based or mobile health (mHealth) interventions^{74, 75} should be considered to test whether they can enhance culturally-appropriate community-based programs. This can include telephone-delivered hypertension management programs^{76, 77} in conjunction with HBPM, or ABPM and/or mobile phone text messaging to support medication adherence.^{78, 79} Smartphone technology can also be used to facilitate data collection, including ecological momentary assessments among JHS participants between study visits and deliver or re-emphasize healthcare education⁸⁰ and lifestyle interventions.^{73, 81}

Summary

This report summarizes the discussion of a working group assembled by the JHS coordinating center to consider potential hypertension research related to the parent study. The working group reviewed several research hypotheses that could be tested with ongoing follow-up of, and additional study visits for, the JHS cohort. Discussions extended beyond observational follow-up of enrolled participants and included randomized interventions and the development of a hypertension registry. A summary of potential research opportunities is provided in Table 2.

Table 2.

Hypertension-related research opportunities for consideration in the next phase of the Jackson Heart Study.

Research Domain	Opportunity
Basic science	Conduct physiological studies of sodium and potassium intake to better understand the relationship of sodium and potassium excretion, and its diurnal pattern, with blood pressure
Basic science	Assess blood pressure independent effects of sodium and potassium intake on cardiac, vascular and kidney function
Basic Science	Assess interaction of sodium and potassium intake with obesity on cardiac hypertrophy/fibrosis, vascular dysfunction/fibrosis, albuminuria/kidney fibrosis
Observational	Estimate the prevalence of, and identify risk factors for, masked hypertension, nocturnal hypertension and non-dipping blood pressure.
Observational	Ascertain the agreement between phenotypes obtained through home blood pressure monitoring and ambulatory blood pressure monitoring.
Observational	Determine the contribution of clock genes to clinic and out-of-clinic blood pressure.
Observational	Create a vascular laboratory to determine the prognostic value of pulse wave velocity, augmentation index, central aortic pressure, systolic and diastolic function, and ankle brachial index.
Observational	Compare blood pressure obtained using an automated device with and without an observer being present.
Observational	Study the level of kidney function at which potassium intake transitions from beneficial to harmful.
Observational	Determine the association of dietary patterns and nutrients on clinic blood pressure and out-of-clinic blood pressure phenotypes.
Observational	Determine the association of sitting time on incident hypertension and blood pressure control among participants with hypertension.
Observational	Assess the association of lead, perfluroalkyl chemicals, cadmium, and arsenic on blood pressure.
Observational	Assess the percentage of uncontrolled blood pressure that can be explained by low adherence assessed using urine metabolites. Determine the major reasons underlying low adherence.
Observational	Develop a hypertension registry in Jackson, MS.
Observational or intervention	Determine the relationship of sodium and potassium intake with blood pressure, vascular function, and cardiovascular disease in African Americans.
Observational and Intervention	Ascertain the effect of West African ancestry on clinic and out-of-clinic blood pressure and whether the blood pressure lowering effect of antihypertensive medication classes differ by ancestry.
Intervention	Determine the benefits and risks associated with treating masked hypertension, nocturnal hypertension and non-dipping blood pressure.
Intervention	Determine the benefits and risks of night-time dosing of antihypertensive medication.
Intervention	Determine whether increasing standing time or moderate physical activity time reduces blood pressure.
Intervention	Determine if interventions to improve sleep hygiene can reduce clinic blood pressure and restore a normal diurnal blood pressure pattern.
Intervention	Determine if tailored interventions aimed at psychosocial health can reduce blood pressure.
Intervention	Assess the association of momentary stressors on blood pressure and whether just-in-time interventions to reduce the effects of stress exposure can lower blood pressure..
Intervention	Determine if tailored interventions aimed at intentional and unintentional reasons for not taking antihypertensive medication as prescribed can improve adherence and blood pressure control.
Intervention	Compare the effect of chlorthalidone versus hydrochlorothiazide on blood pressure and cardiovascular outcomes.
Intervention	Determine the association of APOL1 risk variants and blood pressure.
Intervention	Test the feasibility of implementing a systems-based hypertension control program.
Intervention	Test the effect of a telephone-delivered hypertension management program on blood pressure control.
Intervention	Use smartphone technology to deliver healthcare education and lifestyle interventions and monitor effects on blood pressure control among participants with hypertension.
Intervention	Does moderate reduction in sodium intake or moderate increase in potassium reduce left ventricular hypertrophy, albuminuria, and vascular dysfunction in obese adults with hypertension.