Ms. Jones is a 64-year-old African American woman with a history of hypertension (HTN), type 2 diabetes mellitus, and remote tobacco usage who works as a teller at a bank. She presents with complaints of increased dyspnea on exertion after walking 25 feet. She has noticed bilateral lower extremity edema and has been sleeping in a recliner on the first floor of her home rather than in her bed on the second floor for the past month because of shortness of breath when climbing stairs. Should the diagnosis of heart failure (HF) and management be based upon the patient’s race and ethnicity?

The prevalence of HF in the United States is on the rise, and it disproportionately affects racial/ethnic minorities.^1-5 Currently 5.1 million individuals in the United States have HF.⁶ While the risk of developing HF is 1 in 5 after age 40 years, the prevalence is expected to approach 46% in 2030.^6,7 African Americans have the highest risk of developing HF (4.6 per 1000 person-years), followed by Hispanic/Latinos (3.5 per 1000 person-years), Caucasians (2.4 per 1000 person-years), and Chinese Americans (1.0 per 1000 person-years).^6,7 With the growing populations of racial/ethnic minorities in the United States, including Hispanics and Asians, these minorities will represent an emerging number of HF patients.^8,9 This chapter reviews the burden of HF on different racial and ethnic groups in the United States and appropriate management.

The etiology of HF differs based on racial and ethnic backgrounds.¹⁰ Ischemic disease and HTN are the most common causes of HF in the general population and should be assessed for independent of race and ethnicity upon diagnosis.^1,5,10 In the Multi-Ethnic Study of Atherosclerosis, the development of HF was linked to coronary calcification with Caucasians having the highest prevalence followed by African Americans, Hispanics, and then Chinese Americans.⁷ African Americans who developed HF more commonly had left ventricular (LV) hypertrophy, HTN, diabetes, and obesity, whereas Chinese Americans had rare incidence of LV hypertrophy.^6,7,11 These differences may also be attributed to physiologic (salt sensitivity, vascular reactivity, nocturnal dipping in blood pressure, renin angiotensin-aldosterone activation system), genetic, and environmental factors, which will be discussed later in this review.^10,12,13 Unfortunately many of the large HF clinical trials have failed to include sufficient numbers of racial and ethnic minorities, which limits precision-based care (Table 12-1).¹⁴

The greatest risk factor for HF in African Americans is HTN.¹³ African Americans may have an increased risk factor profile at the time of diagnosis of HF, including HTN, diabetes, and obesity although they present with similar signs of volume overload as other races and ethnicities.^13,15 In the Losartan Intervention for Endpoint Reduction in Hypertension Study, patients with HTN were followed for 2 years post antihypertensive therapy.¹⁶ At the end of the study, LV mass and relative wall thickness were significantly greater in African American than in non-African American patients.¹⁶ The unfavorable remodeling and HTN were hypothesized to be mediated by polymorphisms of the corin I555 allele, which is found commonly in African Americans and rarely in Caucasians.¹⁶ In addition to increased LV mass, studies have shown that African Americans have higher levels of pro-brain natriuretic peptide, which confer increased risk of development of HF.¹²

Genetic predispositions for HF exist in the African American population. African Americans possessing the α2CDel322–325 and β1Arg389 adrenergic receptors have higher risk of developing HF.¹⁷ A dual receptor polymorphism in the beta 1 and alpha adrenergic receptors is seen more commonly in African Americans with HF and is associated with worse outcomes.¹³ A mutation of the beta 3 subunit of the G1 type protein is also overexpressed in some African Americans, and it correlates with HTN, renal disease, and salt sensitivity.¹³ The Genetic Risk Assessment Sub-Study of the African American HF Trial (A-HeFT) has shown that a specific polymorphism of aldosterone synthase exists in a higher frequency in self-identified African Americans.¹⁸ This polymorphism is associated with greater responsiveness to the combination of isosorbide dinitrate and hydralazine.¹⁸

Cardiopulmonary exercise testing is a form of clinical assessment in the HF population, but interpretation should be influenced by race/ethnicity. Peak oxygen consumption and ventilator efficiency are important independent prognostic indicators in HF.¹⁹ However in multivariable analyses, a minute ventilation (VE)/carbon dioxide output (VCO₂) slope provided the most prognostic information independent of race/ethnicity and sex.¹⁹ Furthermore the combination of VE/VCO₂ and oxygen consumption (VO₂) provided additive prognostic information only in Caucasians, and the combination of VE/VCO₂ and LV ejection fraction provided additive prognostic information in African Americans.¹⁹

Key considerations in management of HF in the African American population pertaining to the HF stages set by the guidelines and recommended therapies are reviewed below.^13,20 For complete management and treatment recommendations, providers should look toward the HF guidelines.^13,20

Stage A represents a critically important group because many of the risk factors can be effectively controlled and may prevent the development of cardiac disease and ultimately HF especially in African Americans.¹ Lifestyle modifications for the prevention of HTN include weight reduction, adoption of Dietary Approaches to Stop Hypertension, restriction of dietary sodium, inclusion of daily physical activity, and moderation of alcohol consumption.¹³ Thiazide diuretics represent the cornerstone of HTN therapy in all patients especially African Americans.¹³

Asymptomatic LV dysfunction, stage B, progresses to symptomatic HF much more aggressively in African Americans.^1,13,21 At this stage, specific cardiac structural changes (LV remodeling, LV dilation) may occur including those caused by myocardial infarction, HTN, cardiomyopathies, and valvular heart disease.^13,20 Therapeutic recommendations from HF guidelines for stage B include lifestyle modifications as described for stage A, and patients should be on evidence-based therapy including beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) irrespective of race/ethnicity.²⁰

In stage C HF, there is evidence of structural heart disease and symptoms of HF.¹ At this stage, the guidelines recommend continuing medication therapy, as in stage B patients, and adding an aldosterone antagonist.¹ There are some key differences in response to HF medications in the African American population. In the Beta-Blocker Evaluation in Survival Trial (BEST) study, the use of bucindolol was associated with a nonsignificant increase in the risk of serious clinical events in African American patients, but reduced death or hospitalization in non-African American patients.²² However in the United States Carvedilol Heart Failure Trial with symptomatic HF and ejection fraction <35%, the benefit was of similar magnitude in both African American and non-African American patients.^23,24 The authors proposed that, as compared with other beta blockers, carvedilol might be more effective in African American patients because of its additional alpha adrenergic receptor blocking activity.²⁴ Subanalysis of the Studies of Left Ventricular Dysfunction (SOLVD) study data showed that the response to treatment with the ACE inhibitor, enalapril, was decreased in African Americans.^13,24 Current HF guidelines stress that although African Americans may not achieve the same level of benefit from ACE inhibitors, this class of drugs has been shown to significantly reduce risks of renal disease and cardiovascular mortality and is indicated in the long-term management of HF.^13,20,25 Studies have demonstrated that African Americans receive additional mortality benefit not seen in other races/ethnicities with the addition of hydralazine and long-acting nitrates (Figure 12-1).¹³ The African American Heart Failure Trial and its substudies demonstrated improvements in echocardiographic parameters, rehospitalization, and mortality.²⁶ A possible explanation for the greater efficacy of the isosorbide dinitrate and hydralazine combination in African Americans may be that nitric oxide levels are reduced more and angiotensin II levels are increased less in African Americans with HF compared to Caucasians.²⁶ Genetic studies support this hypothesis, showing that African Americans are more likely to have polymorphisms in certain endothelial nitric oxide synthase genes compared with other ethnic groups.^13,18,25-28 Although there is strong evidence for the benefits of isosorbide dinitrate and hydralazine in self-described African American patients, this therapy remains underused.²⁶ Trials evaluating the aldosterone antagonists spironolactone and eplerenone in chronic severe HF and post myocardial infarction LV dysfunction have demonstrated clinical efficacy, but the numbers of African American participants in those studies have been too few to allow meaningful subset analysis by race.²⁸ However, there is no reason to assume a lack of efficacy, and these agents should be used per published guideline statements in patients irrespective of race/ethnicity.¹³