Improving Approaches to Hypertension Treatment in African Americans: Lessons Learned From the Jackson Heart Study

In this issue of The Journal of Clinical Hypertension, Harman and colleagues report on 2415 persons with treated hypertension (1667 women; 748 men; mean age, 60±11 years) in the Jackson Heart Study (JHS), a community‐based cohort study of 5301 African American adults living in the Jackson, Mississippi, metropolitan statistical area.1 This landmark study was initiated in response to the high prevalence of cardiovascular disease (CVD) among African Americans and is an excellent opportunity to better understand the unique aspects of hypertension and related CVD in African Americans, whose prevalence is among the highest in the world and steadily increasing. Compared with Caucasians, African Americans develop high blood pressure (BP) earlier in life, with much higher average BP and a 1.3‐times greater rate of nonfatal stroke, a 1.8‐times greater rate of fatal stroke, a 1.5‐times greater rate of CVD mortality, and a 4.2‐times greater rate of end‐stage renal disease (ESRD).2

The JHS authors report high‐quality, reliable data on African American adults currently receiving antihypertensive medications and important information about educational attainment and income, which should not be underestimated provided that social determinants of health have a prominent impact on CVD morbidity and mortality beyond race/ethnicity. Morevoer, specifically in many African Americans, socially disadvantaged status has profound effects on CVD risk. In JHS, only 11% of persons lacked any kind of health insurance, with no difference in BP control by insurance status. Nevertheless, there was better BP control with increasing income, although driven by women only, who also had better overall BP goal attainment.

The good news from JHS was the favorable BP control rates in this cohort, compared with 44% in the national rates: 66% and 70% of treated hypertensive participants at examinations I and II, respectively, had a BP <140/90 mm Hg.1, 3 Thiazide‐like diuretics, the most commonly used antihypertensive class in JHS, are likely to remain agents of first choice for most patients, including African Americans, in future US guidelines. Impressively, persons taking a thiazide were more likely to have their BP controlled, although they were used significantly less among men (58% vs 45% [P<.05]), and with less goal attainment than in women. The control of BP in African American men remains a clinical challenge, because it is not well investigated or easily explained. Even among all persons using thiazides, women had a higher rate of BP control than men. The authors suggest that JHS men may be less compliant than women when taking thiazides, perhaps because of the association with erectile dysfunction. However, sildenafil and other phosphodiesterase type 5 inhibitors can be safely used in hypertensive men and may significantly improve male adherence to antihypertensive medications.1

Surprisingly, the authors also noted a significantly lower rate of BP control comparing a calcium channel blocker (CCB), of any class, with thiazide monotherapy, including persons with diabetes and chronic kidney disease (CKD). Nevertheless, CCBs have been shown to be effective as monotherapy in many clinical efficacy studies for African Americans, and JHS is not a randomized clinical trial. Also, the number of persons taking CCB monotherapy was actually small (216 at examination 1; 122 at examination 2).1 Furthermore, with the present widespread availability of generic CCB agents, concern over the cost of acquisition is no longer a prominent barrier and clinicians should not overlook the clear efficacy in 5853 African Americans taking amlodipine compared with 9886 African Americans taking chlorthalidone‐based regimens in the large Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) randomized trial. In ALLHAT, African Americans taking amlodipine demonstrated a reduced diastolic BP, similar to chlorthalidone, and the systolic BP decline with amlodipine was approximately 2 mm Hg less. Importantly, there were no significant differences with amlodipine compared with chlorthalidone in the ALLHAT primary coronary heart disease (CHD) outcome; heart failure in African Americans on amlodipine‐based care was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [CI], 1.24–1.51).4

As noted, the higher rates of CKD in African Americans, including ESRD, requiring dialysis represents an unacceptably high burden of morbidity, mortality, and excess cost of care. Although controversial, the 2010 International Society on Hypertension in Blacks consensus statement advocated inclusion of a renin‐angiotensin system (RAS) inhibitor, angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), as alternative monotherapy options.5 Nevertheless, lisinopril‐based ALLHAT therapy in African Americans demonstrated a greater risk for stroke, combined CHD, combined CVD, and angioedema.4 The 347 JHS hypertensive patients with CKD were associated with lower income (P<.05). However, only 46% were receiving RAS‐blocking medications—either an ACE inhibitor or an ARB—as part of their regimen.1 Nevertheless, ACE inhibitors and ARBs (especially with diabetic nephropathy) have compelling indications to slow the decline of renal function in patients with reduced baseline renal function.6 In the African American Study of Kidney Disease and Hypertension (AASK), a ramipril‐based regimen slowed progression of renal disease in African American participants with hypertensive nephropathy more so than a regimen‐based on metoprolol tartrate or amlodipine.7

The authors wisely note the underappreciated fact that there may be more variation within African Americans than between African Americans and non–African Americans in BP responses as monotherapy to any specific major class of agents.

Moreover, notwithstanding any specific monotherapy responses, most African Americans require combination therapy to control their BP. At examination II, 28% of 731 treated hypertensive patients were receiving monotherapy, but 10% were at least 20/10 mm Hg above BP target, indicating the inappropriate use of monotherapy in these patients.1 An overemphasis or focus on BP responses to any single class of agents in African Americans may be inappropriate, and acceptable pharmacologic antihypertensive drug therapy in most African Americans should de‐emphasize monotherapy. While comparing persons at examination I who received either a CCB, ACE inhibitor, ARB, or β‐blocker (BB) as monotherapy with persons receiving dual‐therapy with any of these medications plus a thiazide diuretic, the individuals taking dual therapy were significantly more likely to attain BP <140/90 mm Hg (71% vs 63%, P<.05).1 Although best practice emphasizes most persons with diabetes or CKD require multiple antihypertensive medications to achieve adequate BP control, >20% of those with diabetes or CKD in the JHS were receiving only monotherapy and 70% of those 74 persons were not at BP target.1 This further unveils the need for better implementation of guidelines and professional recommendations to increase appropriate combination use.

Currently, the optimal initial combination in high‐risk patients is unclear. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension Trial (ACCOMPLISH) was the first combination study with a sizeable sample of African American participants demonstrating the superior ability (hazard ratio, 0.80; 95% CI, 0.72–0.90; P<.001) of benazepril/amlodipine (B+A) to lower CVD morbidity and mortality more than the combination of benazepril/hydrochlorothiazide (B+H).8 In addition, there were 113 (2.0%) events of CKD progression in the B+A group compared with 215 (3.7%) in the B+H group (HR, 0.52; 95 % CI, 0.41–0.65; P<.0001).9 Of the US 8125 participants, B+A therapy was not significantly different from B+H therapy in retarding the rate of progression of kidney disease in 1414 African Americans.10

Thiazide‐like diuretics should appropriately be considered as a component of treatment with resistant hypertension, which is more common in African Americans, and the proportion of persons with treated uncontrolled hypertension receiving <3 medications, a proxy for the rate of therapeutic inertia, was less in the JHS than in national estimates.1, 11 Chlorthalidone was taken by <5% of those in JHS who used a thiazide. While hydrochlorothiazide (HCTZ) may be beneficial in difficult to control patients, chlorthalidone is even more effective, with a longer effective half‐life and preserved efficacy in moderate renal insufficiency. Clinicians who desire to optimize BP control, especially in high risk and difficult to control or resistant patients, including African Americans, would be wise to consider chlorthalidone as the preferable thiazide‐like diuretic. While awaiting an updated US national guideline, a 2008 American Heart Association report noted, compared with HCTZ, chlorthalidone should be preferentially used in patients with resistant hypertension due to superior 24‐hour ambulatory BP reduction, outcome benefit, and superior efficacy.12

The actual reasons for the earlier onset, greater prevalence and severity, and increased target organ damage in African Americans remains to be further delineated. Hypertension in African Americans disparately increases mortality in both men and women, and is a major source of unnecessarily high healthcare costs as a result of myocardial infarction, heart failure, stroke, and ESRD. The JHS is the largest single‐site, prospective, epidemiologic investigation of CVD among US African Americans ever undertaken.13 This population‐based longitudinal study exemplifies a unique collaborative model among 3 institutional partners, the Jackson community, and the National Institutes of Health to report preeminent information available and examine best practices for eliminating health disparities. This report by Harman and colleagues from the JHS provides important insights on the impact of socioeconomic factors and unveils further methods to optimize approaches to pharmacotherapy on BP control in this high‐risk population.