Executive Summary of the African-American Initiative

Abstract

The roundtable discussion, “Managing Cardiovascular Disease in African Americans: Emerging Strategies for Optimizing Care,” was convened to review the evidence that supports best practices for the management of cardiovascular disease and its complications in African Americans. Treatment guidelines are reviewed, as is the clinical evidence supporting the use of diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. The ultimate goals of this work are to improve the understanding of the links among hypertension, diabetes, the metabolic syndrome, and cardiovascular disease, all of which disproportionately affect African Americans, and to increase physician awareness of the unique impact of these conditions in the often underserved African-American population.

Introduction

Cardiovascular disease (CVD) is the leading cause of death for African Americans.[1] They have an increased prevalence of CVD risk factors – such as hypertension, high body mass index, and type 2 diabetes – compared with whites.[2] Despite these increased risk factors, African Americans are not receiving adequate care for CVD and are less likely to receive diagnostic testing, drug therapy, and interventional procedures.[3,4] The mortality rates from hypertension alone were disproportionate in 2003 – 14.9% for white males, 49.7% for black males, 14.5% for white females, and 40.8% for black females.[1]

The roundtable discussion, “Managing Cardiovascular Disease in African Americans: Emerging Strategies for Optimizing Care,” was convened to review the evidence that supports best practices for the management of CVD and its complications in African Americans. The ultimate goals of this meeting were to improve the understanding of the links among hypertension, diabetes, the metabolic syndrome, and CVD and to increase awareness of the unique impact of these conditions in the African-American population.

The purpose of the roundtable was to provide recommendations that: (1) address the need for the improved diagnosis of hypertension, diabetes, ischemia, and coronary artery disease in African Americans; (2) explore strategies to improve translation of promising research results into clinical practice; and (3) assess opportunities for effective educational strategies, including further refinement of key messages to African Americans regarding CVD risk factors and symptoms.

The objectives of the roundtable were to: (1) identify opportunities and needs in current state-of-the art knowledge of racial differences in manifestation, detection, and treatment of CVD in African Americans; (2) identify opportunities and provide recommendations on race-based education for health professionals, patients, and the public; (3) help bridge the gap between therapeutic recommendations and daily clinical practice; and (4) address the disparities in health outcomes and improve pharmacologic strategies for targeting the African-American patient with CVD.

The roundtable experts examined the nature and scope of racial differences in both chronic and acute CVD in terms of clinical manifestations, detection, and treatment. Each roundtable member also expanded on specific areas of expertise in a subsequently published supplement.[5–14] In the conclusions from the meeting, panelists identified the need to develop a unified and comprehensive race-specific strategy for cardiovascular research and education for African Americans in the following areas:

• The disproportionate impact of hypertensive CVD;

• The complexity of choosing an agent in the presence of concomitant illnesses;

• Treatment disparities; and

• Strategies for educating physicians.

Since publication of the supplement, national guidelines have been revised and new clinical trial results have appeared. However, the state of care among African-American patients has not appreciably improved. Thus, this updated summary of the roundtable proceedings is intended to highlight the healthcare disparities that continue to plague the care of African-American cardiovascular patients.

The Disproportionate Impact of Hypertensive Cardiovascular Disease

The intensive treatment of hypertension to target levels in African-American patients is of extreme importance. Hypertension in African Americans develops earlier in life and tends to be more severe, therefore increasing the risk for hypertension-related complications. African Americans have a high prevalence of hypertension, which also increases their risk compared with whites for a variety of associated comorbidities including nonfatal stroke (1.3), fatal stroke (1.8), heart disease death (1.5), and end-stage kidney disease (4.2).[1] Hypertension also contributes more significantly to the etiology of CVD in African-American patients. In the Studies of Left Ventricular Dysfunction (SOLVD) Registry, it was found that coronary artery disease most commonly preceded the development of heart failure (HF) in white patients, whereas hypertension emerged as the primary underlying cause of HF in African-American patients.[15]

Hypertension independently increases the risk of cardiovascular events: as blood pressure (BP) increases, the risks of HF, myocardial infarction (MI), and stroke also increase. Conversely, antihypertensive therapy is associated with a 35%–40% reduction in stroke, a 20%–25% reduction in MI, and a more than 50% reduction in HF.[16] However, hypertension remains undertreated, despite overwhelming evidence that BP reduction results in decreased cardiovascular morbidity and mortality. According to the National Health and Examination Survey (NHANES) data from 1988 to 1991, less than 25% of hypertensive patients had their BP controlled; that percentage increased only slightly in 2000 to approximately 31%. In addition, less than half of hypertensive diabetic patients who were being treated were controlled to a BP level < 140/90 mm Hg, and only a quarter of those patients achieved a goal of < 130/85 mm Hg.[17]

Hypertension rarely exists in isolation, and is often observed with a constellation of other coronary heart disease risk factors such as dyslipidemia, diabetes mellitus, renal disease, and obesity, thus dramatically increasing the risk of cardiovascular events.[10] Diabetes is also more prevalent in African Americans. The 1999–2000 NHANES evaluation of the Centers for Disease Control/National Center for Health Statistics data showed a disproportionately high prevalence of diabetes in African Americans (11.7%) compared with whites (4.8%).[1] African-American women also have a 138% higher rate of medical care visits for diabetes compared with white women.[18] The high rate of hypertension and diabetes in African Americans leads to a high-risk phenotype, and these patients should be treated earlier and more aggressively to lower BP. In diabetic patients, concomitant hypertension increases mortality by as much as 7.2-fold, and the presence of nephropathy increases mortality by as much as 37-fold.[19]

The Complexity of Choosing an Agent

Treatment Guidelines

Effective management of hypertension involves lowering BP to a target goal instead of merely lowering BP, and physicians should use this measure to gauge the effectiveness of therapy. However, the most appropriate target BP goal cannot be determined without a thorough investigation of cardiovascular risk factors and clinical findings. Reducing BP to < 140/90 mm Hg, while adequate for the general population, is inadequate for patients with diabetes or renal disease or for African Americans. These patients should have a target goal of ≤ 130/80 mm Hg, and some clinicians even suggest targets as low as 120/80 mm Hg.[16] In the management of hypertension, increased risk necessitates a greater imperative to reach (lower) target BP goals.

The seventh and most recent report from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recategorized hypertension to account for data indicating that BP levels previously considered normal are associated with increased risk for cardiovascular events. These new guidelines simplified the categorization and lowered the initial threshold of hypertension. Individuals with BP previously considered normal (120-129/80-84 mm Hg) and borderline (130-139/85-89 mm Hg) in JNC VI are now classified to have prehypertension. Patients with BP 140–159/90-99 mm Hg are still classified as having stage 1 hypertension, but those with BP ≥ 160/100 mm Hg are now considered to have stage 2 hypertension. In addition, epidemiologic evidence suggests that systolic BP is a more important risk factor than diastolic BP, thus resulting in the recommendation that practitioners focus on treating systolic BP to target levels, particularly in persons > 50 years of age.[16,20]

JNC 7 enriched the choice of antihypertensive therapy by acknowledging that certain compelling indications warranted combination or multidrug regimens, typically with agents shown to impact the specific concomitant illness. Given the burden of hypertension and the incidence of end-organ disease, an argument can be made that African-American race represents a compelling indication and, as such, one should have a low threshold to consider multidrug and/or combination regimens.

Pharmacologic Management

The chief objectives of therapy for the high-risk African-American patient are thus selecting an adjunctive therapy appropriate for achieving and maintaining a target BP goal. Evidence shows that even slightly elevated BP, either diastolic or systolic, significantly increases the risk of morbidity and mortality. In the United Kingdom Prospective Diabetes Study (UKPDS), diabetic patients randomized to therapy to achieve tight BP control (144/82 mm Hg) had a significantly lower incidence of HF (56% risk reduction; P = .0043) and nonfatal stroke (44% risk reduction; P = .013) than those who achieved less stringent BP control (154/87 mm Hg).[21]

While all antihypertensive agents lower BP in African Americans, and simple regimens appear to work best at reducing cardiovascular outcomes, certain drug classes may have unique cardioprotective effects that would be beneficial in the higher-risk hypertensive patient. The selection of an agent must be guided by the likelihood of drug interactions, the patient's individual risk profile, the ability to access the medication, and race. Clinical evidence suggests that angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and beta-blockers may offer benefits beyond simply lowering BP in patients with comorbid cardiovascular or metabolic conditions.

Monotherapy with a thiazide diuretic is the preferred strategy for any uncomplicated hypertensive patient. Monotherapy with other agents/drug classes may be more or less effective as a function of race. Subgroup analysis of the Vasodilator-Heart Failure Trial-II (V-HeFT) showed that white patients with HF experienced a mortality benefit from enalapril and not from the combination of hydralazine/isosorbide dinitrate, whereas African-American patients with HF experienced an equivalent mortality benefit with enalapril and combination hydralazine/isosorbide dinitrate.[22] The African American Heart Failure Trial (A-HeFT), the only large-scale clinical trial that specifically studied African-American patients with HF and left ventricular systolic dysfunction, demonstrated that outcomes may be improved with use of the isosorbide dinitrate/hydralazine combination as adjunctive therapy for HF in African Americans.[23] Isosorbide dinitrate/hydralazine combination therapy yielded a substantial 43% mortality benefit and a 33% reduction in hospitalizations for HF over background therapy with ACE inhibitors/ARBs and beta-blockers. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which included more than 10,000 African Americans, ACE inhibitors were less effective than either a thiazide-type diuretic or a calcium channel blocker (CCB). African-American patients randomized to an ACE inhibitor had a 40% greater risk of stroke, a 32% greater risk of HF, and a 19% greater risk of CVD than those randomized to a diuretic. However, the interracial differences in BP-lowering observed with these drugs disappeared when they were combined with a diuretic.[24] This observation from ALLHAT should carry over into the clinical domain.

Although BP reduction through lifestyle modification and/or antihypertensive therapy has been shown to dramatically reduce the risk of CVD, recent evidence has shown that many patients with hypertension do not have adequately controlled BP. The JNC 7 guidelines recommend that most patients receive first-line therapy with thiazide diuretics, but the majority of patients will require ≥ 2 antihypertensive agents to achieve adequate BP control.[16] In the African American Study of Kidney Disease (AASK), an average of 3 antihypertensive agents were needed to achieve target BP goals (mean arterial pressure 102–107 or < 92 mm Hg).[25] Combination therapy may be used in most patients and may have synergistic effects that improve BP control, may improve medication compliance, and may reduce the risk of dose-related adverse effects.[16,26] While CCBs and diuretics have been shown to be the most effective therapies for lowering BP in the African-American patient, the patient at high risk for CVD should also be considered for therapy with cardioprotective agents such as ACE inhibitors, ARBs, and beta-blockers that have been shown to provide greater protection against end-organ damage. This protection is the ultimate rationale for their inclusion in antihypertensive therapy. However, combination therapy should be initiated at a lower BP threshold in the African American than in the white hypertensive patient. The recently published International Society on Hypertension in Blacks (ISHIB) guidelines should serve as the guideline for therapy of those patients.[27]

ACE Inhibitors

Activation of the renin-angiotensin-aldosterone system increases the risk of cardiovascular events. ACE inhibitors, by blocking activation of this system, reduce BP and slow the progression of CVD. Despite evidence from ALLHAT showing the superior efficacy of diuretics and CCBs in the African-American patient, ACE inhibitors should be used as part of a multidrug BP-lowering regimen due to important end-organ protection and their renoprotective and cardioprotective benefits. Data from AASK also demonstrated a greater renoprotective effect for ramipril than for the CCB amlodipine in African-American patients with hypertensive nephropathy.[28] Numerous studies also provide evidence for the efficacy of ACE inhibitors in reducing the risk of hypertension-related outcomes.

The randomized, placebo-controlled Heart Outcomes Prevention Evaluation (HOPE) studied the effect of 5 years of treatment with ramipril in patients with evidence of vascular disease or diabetes plus 1 additional risk factor. The primary end point was a composite of cardiovascular mortality, MI, and stroke. Despite only small BP differences by the study end (136/76 vs 139/77 mm Hg for ramipril and placebo, respectively), patients receiving ramipril had a 22% reduced risk of the primary end point (P < .001), with significant reductions in the risk of cardiovascular mortality, MI, HF, and stroke.[29] Diabetic patients treated with ramipril experienced a 25% reduction in the risk of the combined primary end point (P = .0004) compared with patients treated with placebo.[30] Unfortunately, the number of African Americans in HOPE was insufficient to allow extrapolation of these results to the higher-risk African-American patient.

Angiotensin II Receptor Blockers

Recent trial evidence has shown that ARBs, which inhibit the action of angiotensin II by blocking its AT₁ receptors, delay progression to diabetic nephropathy, renal disease, and death in patients with early- or late-stage diabetic renal disease.[31,32] Patients that are unable to tolerate ACE inhibitors may benefit from ARBs.[33] The Valsartan in Acute Myocardial Infarction Trial (VALIANT) showed that the ARB valsartan produced comparable reductions in mortality and morbidity (including cardiovascular death, MI, and/or HF hospitalization) as the ACE inhibitor captopril in post-MI patients with clinical evidence of HF and/or left ventricular dysfunction.[34] An ARB may therefore be a good candidate as an adjunctive agent in the higher-risk hypertensive patient. As there are few race-specific data regarding the use of ARBs, no specific comment can be made regarding efficacy in African-American compared with white patients.

Beta-blockers

Unlike other agents, beta-adrenergic receptor blockers do not exhibit a class effect. While all beta-blocking agents have a powerful BP-lowering effect, they have a heterogeneous effect on peripheral resistance, cardiac output, and metabolic profile. Traditional beta-blockers reduce BP by reducing cardiac output and simultaneously increasing peripheral vascular resistance.[35] By contrast, clinical data indicate that vasodilating, nonselective beta-blockers have positive effects on renal hemodynamics, including improving renal blood flow and glomerular filtration rate in HF patients.[36] Data from the Carvedilol or Metoprolol European Trial (COMET) also indicate that carvedilol may offer more protection against major vascular events in patients with HF when compared to a non-evidence-based formulation of metoprolol tartrate. Carvedilol significantly reduced cardiovascular (20% risk reduction; P = .0004)[37] and stroke mortality (67% risk reduction; P = .0006)[38] compared with metoprolol tartrate.

Beta-blockers are cardioprotective drugs that should be included in a multidrug therapy regimen in the African-American patient. Studies have confirmed that beta-blocker treatment significantly reduces mortality in patients after an MI.[39,40] Unless otherwise contraindicated, beta-blockers should be considered for all patients after an MI, including African Americans and those with type 2 diabetes.[41]

Hypertensive patients without a prior MI also seem to benefit from beta-blockers. Patients randomized to metoprolol tartrate in the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial were at significantly lower risk of all-cause mortality (22% risk reduction; P < .028) and cardiovascular mortality (26% risk reduction; P = .012) compared with patients randomized to thiazide diuretics.[42]

Studies have shown that some beta-blockers are more effective than others in the African-American population. The Beta-Blocker Evaluation Survival Trial (BEST) showed that bucindolol did not have any mortality benefit in African-American patients with HF.[43] Subgroup analysis of the placebo-controlled Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) indicate that treatment effects of long-acting metoprolol succinate in African-American patients may be effective, but the analysis was compromised by the small number of African Americans in the MERIT-HF trial. Although total mortality and hospitalization was reduced to a similar degree in African Americans and non-African Americans, metoprolol succinate did not appear to be as effective in reducing total mortality or total mortality and HF hospitalization in African-American patients.[44,45] Because the number of African Americans in the MERIT-HF trial was low, one should avoid any truly definitive statements, and the practitioner should not be hesitant in prescribing this evidence-based therapy. Propranolol treatment in the Beta-Blocker Heart Attack Trial (BHAT) resulted in comparable mortality reductions in both African-American and white patients after an MI,[39] and a number of trials has shown carvedilol to have cardioprotective benefits in African-American HF patients[46] In the community-based Coreg Heart Failure Registry (COHERE), carvedilol treatment had similar results in reducing hospitalizations, HF, and death in African-American and white patients.[47]

Traditionally, the use of beta-blockers has been discouraged in the diabetic patient due to their negative metabolic consequences,[48] and the significantly higher prevalence of diabetes in African Americans[1] may be one reason for their underuse in this population. Physicians may be reluctant to add a beta-blocker to therapy with thiazide-type diuretics because both drugs precipitate or increase insulin resistance, but this may not represent a class effect. Results from COMET revealed that carvedilol treatment reduced the incidence of new-onset diabetes-related adverse events by 22% compared with metoprolol tartrate treatment (P = .04).[49] In addition, the Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial demonstrated that carvedilol had neutral or beneficial effects on metabolic parameters while metoprolol tartrate had deleterious effects in a population of diabetic hypertensive patients. Almost 15% of the GEMINI subjects were African Americans,[50] and a subgroup analysis revealed that the benefits of carvedilol treatment remained consistent in African-American patients. Carvedilol did not produce a treatment-by-race interaction in change from baseline HbA_1c (P = .830).[51] There was also a significant between-treatment effect for insulin resistance favoring carvedilol in African-American patients (−17% vs 8.2%; P = .01).[51] (Robert A. Phillips, personal communication; David S.H. Bell).

More evidence is emerging that beta-blockers may play a role in preventing arrhythmias. The use of beta-blockers as antiarrhythmic agents should be not overlooked in the African-American population. Sudden death may be more common in the young African American, and beta-blockers are among the few therapies that have been shown to reduce the incidence of sudden death.[52,53] Arrhythmias and sudden death are common after an MI. A blinded posthoc analysis of arrhythmic events identified from the adverse events database of the placebo-controlled Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial showed that carvedilol had a marked beneficial effect on arrhythmias when added to an ACE inhibitor.[54]

Treatment Disparities

The burden of hypertension and diabetes coupled with poor treatment strategies for the African-American patient leaves this population at great risk for CVD. The African-American population remains severely undertreated despite guideline recommendations and attempts to improve treatment. According to recent NHANES data, 35% of patients with diabetes achieved their BP goals and less than 10% of diabetic patients had all vascular risk factors (HbA_1c, BP, cholesterol) under control.[55] Although approximately 60% of both African Americans and whites were being treated for hypertension, only 45% of African Americans had their BP under control compared with 56% of whites. These appallingly small numbers of adequately treated patients indicate that most of the population is vulnerable to poor BP control and subsequent cardiovascular risk. Although the NHANES population was only 19% African American, it is likely that a sample of only African Americans would have yielded similar or worse results.[17]

On the basis of these statistics, it appears that physicians are not prescribing adequate therapy for African-American patients. In fact, the underutilization of cardioprotective therapy is marked. The use of ACE inhibitors and beta-blockers has increased but is still at suboptimal levels overall and at severely suboptimal levels in African-American patients. In a study of post-MI patients, only 32% of African Americans were treated with a beta-blocker at discharge.[39]

Strategies for Educating Physicians

While the disproportionate impact of CVD on African Americans may in part be due to genetic factors, it is undeniable that environmental risks and treatment differences exist. The African-American population is treated less aggressively for CVD, and it was shown in one study that revascularization procedures are less likely to be performed in African-American than in white patients.[56] Physicians may require both educational tools and specific guidelines for providing care to African-American patients, and they may need to have a heightened awareness of the risk factors for hypertension and the early markers of target-organ disease. They also need clear, evidence-based clinical guidelines for specific interventions, used singly and in combination, to achieve optimal outcomes. New guidelines for screening and treating BP should be applied to all patients, including African Americans. In addition, physicians need guidelines to screen for other potentially critical clinical markers such as impaired glucose tolerance, microalbuminuria, and central obesity. There are a number of barriers to achieving adequate BP goals in African-American patients, but it is possible to overcome these barriers by refuting the misconceptions that BP goals are not achievable in this population, that medication is not tolerated, and that certain medications do not work in African-American patients.

A New Paradigm for Treatment

Prior to focusing on novel treatment approaches, it is imperative to acknowledge that more research is needed to better understand the context of race in medicine. Race per se is neither physiologic nor scientific, but rather refers to a grouping of individuals with similar inherited traits and shared environmental stresses. The physiologic determinants of the excess in CVD burden and/or the important psychosocial and socioeconomic factors that contribute to this disease burden need further clarification.

Nevertheless, a new paradigm for the treatment of the African-American patient at risk for CVD is necessary since it has become clear that we, as physicians, have failed to properly and adequately treat this high-risk population. This new paradigm needs to encompass a comprehensive patient assessment for treatment that includes race, family history, and concomitant conditions in addition to earlier treatment with appropriate agents. Physicians should be familiar with antihypertensive agents and should employ them more frequently.

Compared with whites, African Americans are at greater risk for developing a myriad of cardiovascular, metabolic, and renal conditions as well as their associated complications, which mandates the need to regularly obtain BP measurements and to assess CVD risk in this population in the primary care setting.[33] It is also important to take gene-environment interactions into account when deciding on therapy, and it should be a priority to increase awareness among African Americans of the important role that lifestyle choices play in cardiovascular and renal outcomes.

Physicians should be aware if their patient has multiple (cardiovascular) risk factors such as hypertension, diabetes, metabolic syndrome, glucose intolerance, dyslipidemia, history of cigarette smoking, obesity, or poor diet. A patient with more than 1 risk factor should be treated aggressively. In addition, it is important to appropriately treat concomitant diseases, since the patient with hypertension may also have HF, diabetes, or renal disease. It is the task of every physician to overcome the myth that it is more difficult to treat hypertension in African-American patients.

It is paradoxical that the patients who would benefit the most from the use of certain antihypertensive agents are the ones who do not receive them. The markedly inadequate use of these guideline-recommended, evidence-based therapies for the management of CVD in African-American patients strongly suggests the urgent need for newer strategies to increase their use. This situation must change, and it is the responsibility of every caring physician to ensure that this high-risk patient population receives proper and adequate medical treatment.

Roundtable Participants

Following are the faculty that participated in the “Managing Cardiovascular Disease in African Americans: Emerging Strategies for Optimizing Care Roundtable.” April 24–25, 2003, in Washington, DC. They did not participate in the writing or review of this executive summary. Please refer to the supplement in The Journal of Clinical Hypertension, Supp. 1, Vol. VI, No. IV, April 2004, to view the papers that these faculty wrote following the roundtable.

Co-Chairs

James R. Gavin III, MD, PhD, Emory University School of Medicine, Atlanta, Georgia

Clyde W. Yancy, MD, FACC, Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas

Faculty

Jean-Bernard Durand, MD, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Gary H. Gibbons, MD, Morehouse School of Medicine, Atlanta, Georgia

Kenneth A. Jamerson, MD, University of Michigan Health Systems, Ann Arbor, Michigan

Elijah Saunders, MD, FACC, FACP, University of Maryland School of Medicine, Baltimore, Maryland

Domenic Sica, MD, Virginia Commonwealth University, Richmond, Virginia

Panelists

Peter Carson, MD, Georgetown University School of Medicine and Veterans Affairs Medical Center, Washington, DC

Charles Curry, MD, Howard University College of Medicine, Washington, DC

Patricia Davidson, MD, Howard University Hospital, Washington, DC

Roy Flood, MD, Howard University Hospital, Washington, DC

Shauna Nesbitt, MD, The University of Texas Southwestern Medical Center at Dallas, Texas

Steven N. Singh, MD, Georgetown University School of Medicine and Veterans Affairs Medical Center, Washington, DC

James Sowers, MD, University of Missouri, Columbia, Missouri

Deborah Williams, MD, Howard University Hospital, Washington, DC

Funding Information

This work was supported by GlaxoSmithKline, Philadelphia, Pennsylvania.