Hypertension is a major contributor to the global disease burden and is one of the leading preventable causes of premature death worldwide.1 In the US, a disproportionate burden of hypertension and its associated complications—including coronary heart disease, heart failure, stroke, and end-stage renal disease and cardiovascular disease mortality—affect African-Americans (also referred to as US blacks).2 This excess burden of hypertension among African-Americans has been recognized since early in the 1900s and explains a substantial portion of health disparities in this population.3–5 The goal of this review is to provide an update of the current research on hypertension in African-Americans through a brief description of the epidemiology, pathophysiology, and management of hypertension.
The rates of hypertension in various populations of African ancestry have geographical variances related to high sodium intake, low potassium intake, obesity, and inactivity. As such, African-Americans have one of the highest rates of hypertension worldwide—much higher than other populations of African origin.6 Compared with white Americans, hypertension is not only more prevalent in this population, it is also observed at an earlier age, has greater severity, and is accompanied by a disproportionate level of target organ damage (1.8-fold higher rate of stroke, 4.2-fold higher rate of end-stage renal disease, 1.7-fold higher rate of heart failure, 1.5-fold higher rate of coronary heart disease mortality).2
Hypertension represents a risk across the lifespan. Perhaps the most alarming epidemiological data regarding hypertension among African- Americans come from studies of children and adolescents. Data from the Bogalusa Heart Study, a bi-racial cohort study conducted in the state of Louisiana including approximately 3,500 school-age children, demonstrate that beginning at age 10, African-American children had significantly higher blood pressure (BP) values than did white children.7,8 Data from other studies confirm that elevated blood pressure begins as early as pre-adolescence and children who remain in the highest 90th blood pressure percentile are more likely to evolve toward permanent hypertension or early target organ damage in young adulthood.9–11
The prevalence of hypertension varies by both race and gender, with the highest prevalence rates observed among African-American women. Although not specifically described by race/gender, the age-adjusted prevalence of hypertension in the 2003–2004 National Health and Nutrition Examination Survey (NHANES) was 39.1% for African-Americans compared with 28.5% for white Americans.12 Earlier race-/gender-specific data from NHANES 1999–2004 indicate that the age-adjusted percentage of persons with hypertension, defined as >140/90mmHg or taking antihypertensive medication, has actually increased in the US, to 41.4% for African- American females and 39.0% for African-American males versus 28.5% for non-Hispanic white males and 28.0% for non-Hispanic white females.2
The burden of death related to hypertension is significantly higher in African- Americans. In 2004, the overall death rate from hypertension was 17.9 compared with 49.9 and 40.6 for African-American men and women, respectively.2 These higher mortality rates are consistent with poor levels of BP control among African-Americans. Despite 66.4% of African-Americans being aware of their hypertension and 55% treated, only 28.9% achieve BP control compared with 33.1% controlled in the overall population.12 In addition to poor rates of BP control, US blacks have been under-represented in clinical trials, limiting the usefulness of trial results in guiding pharmacological therapy in management of hypertension among African-American patients. However, recent trials have attempted to recruit larger numbers of African Americans and may provide insight into pharmacological management in this population.
Researchers have noted that some African-Americans may have unique pathophysiology related to a greater prevalence and severity of hypertension, including factors involving the epithelial sodium channels, renin-angiotensin-aldosterone system (RAAS), adrenergic receptors, nitric oxide pathways, and transforming growth factor hyperexpression.
Increased sodium absorption and salt sensitivity appear more common and prominent in African-Americans, perhaps related to the epithelial sodium channel. The T594M allele of the epithelial sodium channel β-subunit has been described in persons of African origin, yet not commonly in whites, and may be a potential pathway for the increased risk of salt-sensitive hypertension.13 Furthermore, African-Americans more commonly appear to have an increased favorable response to thiazide diuretics, perhaps related to a higher risk of the C825T polymorphism of the gene encoding the β3 subunit of the G protein.14
Additionally, transforming growth factor has been found to be elevated in some African-Americans with hypertension and may also be associated with salt-sensitive hypertension. 15 This inflammatory cytokine may increase extra-cellular matrix and fibrosis and may lead to target organ damage.16 In addition, African-Americans may have a blunted nocturnal decline in blood pressure, or absence of dipping. This absence of nocturnal decline may be a marker of more severe hypertension and target organ damage.17,18
Target Organ Damage
In the African-American population, target organ damage—including stroke, hypertensive nephropathy, end-stage renal disease, left ventricular hypertrophy (LVH), coronary heart disease, and heart failure—is more common and severe. At the younger ages of 35–54 years, African-Americans have approximately four times greater stroke rate than white Americans.2,3 The increased prevalence of renal insufficiency and end-stage renal disease represent an independent adverse cardiovascular risk. Moreover, LVH is more common and severe in African-Americans at all levels of blood pressure, which may be related to an increase in sudden cardiac death.2
Heart failure in African-Americans has a lower incidence of associated atherosclerotic coronary artery disease and is more likely associated with hypertension. African-Americans have increased rates of hospitalization and mortality with heart failure and are often younger and have more advanced left ventricular dysfunction at the time of diagnosis. Data from the African- American Heart Failure Trial (A-HeFT) found that African-American patients with advanced heart failure fared better when given a fixed dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in addition to standard care, which included angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and beta-blockers (BBs). Specifically, FDC I/H treatment in African-American patients with moderate to severe heart failure who were also taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for heart failure.19 The A-HeFT trial was terminated early due to a 43% reduction in all-cause mortality (p=0.01), a 33% relative reduction in first hospitalization for heart failure (p=0.001), and improvement in quality of life (p=0.02) in the FDC I/H group compared with placebo.20
A recent analysis of A-HeFT data interestingly shows that patients with lower systolic blood pressure had a greater risk but a similar relative benefit from the use of FDC I/H to those with higher systolic blood pressure. These data confirm that an asymptomatic low systolic blood pressure should not be considered a contraindication to use of FDC I/H in African-American patients with heart failure.21
Management of hypertension in blacks has special challenges, including a lack of trial data especially with newer agents on which to base clinical decisions and weigh risks and benefits. However, blood pressure control is not only achievable but mandatory. As a general principle, the most recent guidelines on prevention, diagnosis, and treatment should be followed when treating individuals with elevated blood pressures.22–24 More recently—according to The Department of Health (England) National Institute for Health and Clinical Excellence (NICE) guidelines— lifestyle modification is needed with or without medication in all patients with hypertension and augmented with pharmacological intervention as indicated.24 Additionally, NICE recommends that in black patients of any age, the first choice for initial therapy should be either a calcium-channel blocker or a thiazide-type diuretic.24
The appropriate use of lifestyle modification is the primary means of prevention and early treatment of hypertension in blacks. Blacks should be counseled to avoid sedentary lifestyle, excess dietary sodium intake, low potassium intake, and excessive consumption of alcohol.22–24 The best example of clinical evidence improving lifestyle in this population is the Dietary Approaches to Stop Hypertension (DASH) trial, which established the importance of a heart-healthy eating plan for lowering blood pressure. Sixty percent of the DASH cohort was African-American and interestingly, greater BP reductions were observed in African-Americans compared with whites.25 Several other clinical studies have demonstrated the benefit of educating African-Americans regarding identifying sodium levels in prepared foods, using fresh fruits and vegetables and other sources of potassium and low-fat dairy products, restricting calories, and increasing physical activity.26–28
Pharmacological Clinical Trials
Recently, there has been an increase in major randomized trials with large numbers of African-Americans, such as the National Heart, Lung, and Blood Institute-sponsored Antihypertensive Lipid-Lowering in Heart Attack Trial (ALLHAT), the African-American Study of Kidney Disease and Hypertension (AASK), and the International Verapamil/Trandolapril Study (INVEST).29–31 These landmark trials confirmed the benefit of using thiazide-type diuretics, long-acting calcium channel blockers (CCBs), and ACE inhibitors with hypertensive nephropathy and proteinuria to achieve BP reduction and beneficial outcomes in hypertension-related cardiovascular and renal disease. The largest antihypertensive trial ever designed—ALLHAT (n=42,448)—included a significant 35% black population (n=15,133).29 There was no difference among therapies based on chlorthalidone, lisinopril, and amlodipine in preventing major coronary events. However, in the black cohort, chlorthalidone—the thiazide-type diuretic—demonstrated superior efficacy to lisinopril and amlodipine in reducing heart failure; also, compared with lisinopril, a 40% decrease in stroke and a 19% decrease in overall cardiovascular disease was observed.29
Despite a compelling benefit as indicated by AASK, a randomized, double-blind, controlled trial with 1,094 nondiabetic African-Americans with hypertensive renal disease, some clinicians under-prescribe ACE inhibitors in African-Americans.30 In the AASK trial, almost 80% of the patients were able to lower blood pressure to <140/90mmHg.30 Furthermore, ramipril-based therapy reduced the decline in kidney function to a significantly greater effect than did therapies based on amlodipine or metropolol, especially in patients with proteinuria.30
The advantage of a long-acting CCB strategy (verapamil–trandolapril) combined with an ACE inhibitor versus a non-CCB strategy (atenolol– hydrochlorothiazide) in 22,576 hypertensive patients with co-existing atherosclerosis and/or diabetes was demonstrated in INVEST.31 INVEST was a randomized, open-label, blinded, end-point study. The primary outcome was the first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke. The 3,029 African-American INVEST participants had higher rates of diabetes, LVH, and smoking, but appeared to have similar benefits with the calcium antagonist strategy with the primary outcome and BP reduction compared with the general INVEST cohort.31
Selection of Pharmacological Agents
The response of any individual to a medication cannot be predicted based on race. Nevertheless, single-drug therapy for hypertension in US blacks may be more effective with thiazide diuretics and CCBs versus BBs or ACE inhibitors. However, one drug is usually not adequate to control BP in this population; as such, most blacks will require treatment with two or three antihypertensive agents of different classes to achieve goal BP.31 Therefore, the clinical decision to use a specific drug ultimately should be based on other considerations, such as efficacy in individual patients, compelling indications, and cost.
African-Americans respond well with thiazide diuretics as first-line therapy for BP reduction, stroke, and cardiovascular risk benefits. However, when single-drug therapy is not sufficient, the thiazide diuretics increase the efficacy of ACE inhibitors, ARBs, and BBs. Long-acting CCBs, both dihydropyridine and non-dihydropyridine, have been shown to reduce BP effectively in blacks and to reduce stroke and cardiovascular events.29,31
The use of RAAS-blocking agents in African-Americans is controversial considering that monotherapy with ACE inhibitors, ARBs, and BBs demonstrate fewer BP-lowering effects. Regardless, aldosterone antagonists such as spironolactone and eplerenone may have equal efficacy in African-Americans versus whites. A rare but unique complication of ACE therapy is the higher rate of angioedema in African- Americans: for instance, in ALLHAT, 0.72% (23 of 3,210) in African Americans versus 0.31% (18 of 5,844) in non-African-Americans.29 The cause of increased rates of angioedema in African-Americans is unclear, but patients should be informed of this potential side effect, which appears increased, along with cough, in this population. Data on the benefit of ARBs are somewhat lacking in blacks. In the Losartan Intervention for End-Point Reduction in Hypertension (LIFE) study, the 533 African-Americans of over 9,000 patients with hypertension and LVH randomized to the ARB (losartan regimen) versus the BB (atenolol regimen) actually showed a less effective decrease in cardiovascular morbidity, including stroke, with losartan-based therapy. However, this subgroup finding may be due to chance, since the sample size of African- Americans was small.32
Although ACE inhibitors and ARBs are protective against diabetic nephropathy, in high-risk African-American hypertensive patients diuretics or CCBs are usually needed to control BP effectively. After a myocardial infarction, BBs should be used in all patients. A novel BB, nebivolol, has been shown to restore nitric oxide bioavailability in African-Americans and may be effective in high-risk African-American hypertensive patients.
African-American patients represent a unique population with regard to hypertension, ranging from the etiology of the disease to selection of and response to treatment. However, in the final analysis, race (i.e. skin color) may only have benefit as a crude proxy for unmeasured variables related to socioeconomic status, culture, health-seeking behavior, and patient–physician communication. Furthermore, the successful management and control of BP among African-Americans, or any population, depends on the ability to identify patients, the effectiveness of the pharmacological agents, and the degree of compliance with the treatment regimen. Even though research may have indicated nuances of medication benefits and risks in African-Americans, life-saving therapy, including compelling indications for antihypertensive medications, should be utilized in African-Americans similar to in Caucasians according to the current clinical practice guidelines.