Management of Hypertension in African-Americans

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Abstract

The prevalence of hypertension and its consequences remain high in African-Americans, and both treatment and control are lagging behind that seen in the general population. The reasons for this phenomenon are found in physiological, cultural, and socioeconomic differences. It is important to properly frame these differences in the approach to management of blood pressure in this high-risk population. In this article, these factors are discussed along with a review of recent clinical trial implications for treatment approaches in African-Americans. In managing African-American patients with hypertension, it is important to: assess the overall cardiovascular risk and blood pressure goal; define the amount of blood pressure reduction required; select the drug according to the patient’s clinical profile; choose the dose according to the dose–response curve for ethnic populations, if known; consider the socioeconomic, lifestyle, and educational background of the patient in making drug choices; and, most importantly, educate patients on the disease, treatment, expectations, and lifestyle recommendations.

Disclosure
Shawna D Nesbitt, MD, MS, is a consultant or on the speaker's bureau for Novartis, Boehringer Ingelheim, BMS-Sanofi, Forest Pharmaceuticals, and Daichii Sankyo Pharmaceuticals, and carries out research for Forest Pharmaceuticals.
Correspondence
Shawna D Nesbitt MD, MS, Associate Professor of Internal Medicine, University of Texas Southwestern Medical Center, 5303 Harry Hines Blvd, U9.408, Dallas, TX 75390-8586. E: Shawna.Nesbitt@UTSouthwestern.edu
Received date
28 August 2009
Accepted date
18 September 2009
Epidemiology

Hypertension is both more common and more destructive in African-Americans than in other ethnic groups. According to the 2005–2006 National Health and Nutrition Examination Survey (NHANES) data, the current prevalence of hypertension in African-Americans is 39.1%, which is well above non-Hispanic whites at 28.5%. While awareness and treatment rates are similar between African-Americans and non-Hispanic whites (66.4 versus 66.9% and 55.0 versus 53.7%, respectively), blood pressure control among all hypertensives is lower in African-Americans (28.9%) compared with whites (35.4%).1 Furthermore, the mortality rate from hypertension in African-American men and women (52.1 and 40.3%, respectively) is higher than in non-Hispanic white men and women (15.8 and 15.1%, respectively.2 Similarly, the disparity in hypertension is prominent in children. The estimated prevalence of elevated blood pressure (including hypertension and pre-hypertension) is higher among African-American compared with white adolescents (24.5 and 17.5%, respectively).3 In an analysis of NHANES data from 1988 to 1994, African-Americans were twice as likely as the other groups to have four or five cardiovascular risk factors.4 The need for greater attention to the management of blood pressure in African-Americans is obvious.

Contributing Factors to Hypertension Disparity and Treatment in African-Americans

There are several physiological and hemodynamic determinants of hypertension in African-Americans. Although there is speculation about possible differences in etiology and pathophysiology, no single, unique cause of hypertension has been identified that explains the high prevalence of hypertension in African-Americans. Obesity is a major contributing factor to hypertension. This association is thought to be due to an increase in factors such as angiotensin, leptin, and renal medullary compression, leading to increased sympathetic nervous system activation, and decreased adiponectin, leading to elevated blood pressure and increased cardiovascular risk.5,6 Harshfield and others have shown that obese African-Americans have higher rates of sodium retention than whites, and that the percent body fat is related to sodium retention.7 Importantly, the prevalence of obesity is highest in African-American women, at 35.7%. African-Americans have a 51% higher prevalence of obesity, and Hispanics (28.7%) have 21% higher obesity prevalence compared with whites (23.7%)8 The rapid rate of growth of obesity in African-Americans in particular predicts a likely increase in hypertension. Another frequently cited etiological factor is salt sensitivity among African-Americans. Salt sensitivity is described as an increase in blood pressure in response to a high-salt diet.

Physiological studies of hypertensives indicate that the prevalence of salt sensitivity in African-Americans is 50%, whereas the prevalence in whites is 40%.9,10 Thus, not all hypertension is explained by salt sensitivity in African-Americans. Recent investigations of genetics suggest that the T594M variant polymorphism explains some of the variance in blood pressure (BP) response to salt intake; however, this particular gene is infrequent, occurring in 5% of African-Americans, and it is estimated to explain only 3% of the variance in response.11 There has been speculation that the salt-sensitivity phenotype is a ‘survival response’ in African-Americans related to the transatlantic slave trade and the hardship invoked; however, there is no firm biological proof of this concept. At this point there are no specific genes that completely explain the disparity of hypertensive disease in African-Americans.

Other physiological changes have been described in African-Americans, such as increased alpha receptor sensitivity, decreased beta receptor sensitivity, increased sympathetic nervous system activity due to stress, increased endothelin, increased transforming growth factor-beta (TGF-β1), decreased prostaglandin E2, decreased urinary dopamine after salt loading, and a decrease in atrial natriuretic peptide (ANP) after salt loading. However, none of these physiological findings is unique to African-Americans.12–21 Recently, investigators have identified differences in the balance of endothelial nitric oxide (NO) and reactive oxide species (ROS) between African-Americans and whites. It appears that, in healthy individuals, African-Americans have a relative reduction in the NO/ROS ratio compared with whites.22 Thus, the vasculature has less available NO for ‘natural’ vasodilation.

These physiological changes may have some bearing on the best drug choices for treatment in African-Americans. In as much as physiology is important in the management of hypertension in African-Americans, the environment, sociology, and culture have a significant effect on treatment. Socioeconomic disadvantage and poor access to care play a role in the excess burden of hypertension. Interestingly, the rate of hypertension in blacks living in America is higher than in blacks living in Africa. This difference is more striking in Africans living in rural Africa, where the rate of hypertension is much lower than in urban Africans, highlighting the importance of the environment in hypertension.23–25

Perceptions about hypertension among African-Americans may affect behavior in terms of compliance and adherence to therapy. In a survey of hypertensive African-Americans, patients had appropriate clinical expectations of their role in treatment, the desire to be educated by their physicians, and the belief that medications would lower BP and the risk of complications from hypertension.

However, most of these African-Americans also had inappropriate, non-biomedical expectations of their treatment: 38% expected a cure, 38% did not expect to take antihypertensive medications for life, and 23% took medications only with symptoms.26 These known factors play a role in the disparity of hypertension control in African-Americans and therefore are important to consider in developing treatment plans.

Treatment Options

Diet and exercise remain the essential features of treatment recommendations for hypertension, especially given the obesity rates in this population. The Dietary Approaches to Stop Hypertension (DASH) study has demonstrated efficacy in reducing BP. It was particularly effective in African-Americans, producing impressive BP lowering even without weight loss or reductions in dietary sodium intake. The combination diet reduced BP by 13.2/6.1mmHg among African-Americans with hypertension and by 4.3/2.6mmHg among normotensive African-Americans. By comparison, in whites the reduction in BP was 6.3/4.4mmHg in hypertensives and 2.0/1.2mmHg in normotensives.27,28 The difficulty with DASH in African-Americans, as with all populations, is long-term maintenance and adherence to the diet without support.

While it is well known that all of the available antihypertensive classes of drug reduce blood pressure to some extent in all hypertensives, the Veterans Affairs (VA) Cooperative study showed that BP response to various drug classes differs by ethnicity and geographical residence. This implies that BP response is affected by genetic as well as cultural and environmental determinants. African-Americans had the best BP response to the calcium channel blocker and diuretic treatment arm in both the VA Cooperative and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) studies.29,30 In several studies, the BP response to renin–angiotensin system (RAS) blockers in African-Americans is less robust than in whites.30,31 Despite this, the African-American Study of Kidney Disease and Hypertension (AASK) demonstrated that protection from renal disease progression was most improved with an angiotensin-converting enzyme (ACE) inhibitor compared with beta-blocker- or calcium-channel-blocker (CCB)-based therapy.32 In addition, it is important to remember that the primary outcome of the reduction in cardiovascular events in ALLHAT was equivalent between diuretics, calcium channel blockers, and ACE inhibitor therapy.30 Historically, African-Americans have been less responsive to beta-blockers than whites, in particular to traditional beta-blockers.33,34

However, the data for the newer vasodilating betablockers (carvedilol, labetalol, and nebivolol) differ from older agents with respect to beta-adrenoceptor affinity and selectivity and partial agonist activity, which may affect the BP response in clinical use. Early studies of nebivolol demonstrate that part of the mechanism is based on increasing the availability of the natural vasodilator, NO.35 At baseline, African-Americans have less available NO in endothelial cells in vitro; however, the NO balance is restored in the presence of nebivolol.36 In a study of 300 African-Americans treated with nebivolol, the drug reduced BP safely and effectively with a nearly 60% response rate.37 BP response in African-Americans on labetalol is better than with the beta- 1-selective blocker atenolol.38 Similarly, Jawa found that carvedilol is more successful in African-Americans than metoprolol in reducing BP. 39 However, in a trial of heart failure, BP response to carvedilol was not significantly different from that of whites in the study.40

While the discussion of responses to monotherapy in African-Americans is important, given the severity of hypertension and high prevalence of comorbidities in African-Americans the most common scenario is likely to be combination therapy. In the ALLHAT study with 36% African-American participants, the average number of medications was two. In the AASK study, the average number of medications was nearly four.32 There have been only a few trials of combination therapy in hypertension and only one had African-American participants.41–43 The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) of high-risk hypertensives showed that an ACE inhibitor/CCB combination was superior to beta-blocker/thiazide diuretic treatment in the reduction of cardiovascular mortality. However, there were no black patients in this trial. The second combination therapy trial is the Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study, which compared the effects of ACE inhibitor/CCB with ACE inhibitor/thiazide therapy on cardiovascular mortality and morbidity in high-risk patients with hypertension. The study of 11,400 patients, including 11.9% African-Americans and 60% diabetics, showed that ACE inhibitor/CCB reduced cardiovascular disease mortality and morbidity by 20% more than ACE inhibitor/thiazide over five years.43 Furthermore, 24-hour ambulatory BP monitoring demonstrated similar BP control in both study arms.44

There have been no published analyses by ethnicity from the ACCOMPLISH study. These two trials suggest that RAS blockade + CCB is a favorable combination compared with other options in reducing cardiovascular mortality, although the underlying reason for this success remains unclear. Additional studies may further elucidate the optimal combination for specific patient profiles. The ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a comparison of combination RAS blockade with ACE inhibitor/angiotensin II receptor blocker (ARB) (ramipril/telmisartan) or RAS monotherapy with ARB (telmisartan) with RAS monotherapy with ACE inhibitor (ramipril).45 All three study arms reduced cardiovascular mortality and morbidity similarly despite somewhat greater BP reduction in the combination (ACE inhibitor/ARB) group. This trial of 25,570 included only 2.5% blacks, thus there is limited power to make any statements that are specific to blacks. Other, smaller studies have shown that combination ACE inhibitor/ARB therapy reduces proteinuria in patients with renal disease better than monotherapy with ACE or ARB, while a secondary analysis of renal outcomes in ONTARGET did not show such benefits.46,47 The ONTARGET population, however, had minimal renal disease relative to the patients in previous renal studies. Thus, this particular combination of RAS blockade with both ACE inhibitor/ARB may not be ideal for cardiovascular protection in patients without proteinuric renal disease, yet with renal disease it remains a reasonable choice for treatment. There are only two small studies of dual RAS blockade with the direct renin inhibitor (DRI) aliskerin and ACE inhibitor or ARB. These trials do show benefit in reducing target organ damage such as left ventricular hypertrophy (LVH) or albuminuria without significant increase in adverse events,48–51 yet there are no ethnic-specific data from these trials.

The International Society on Hypertenson in Blacks (ISHIB) consensus statement on hypertension in African-Americans, published in 2003, suggested that African-Americans should be managed aggressively with combination therapy when BP was 15/10mmHg greater than their BP goal. The recommended goals for treatment were initially <130/80mmHg for hypertensives with diabetes and chronic kidney disease, while the goal for other hypertensives was <140/90mmHg.52 However, more recently other high-risk patient profiles have been added to the more aggressive treatment goal. Individuals with heart disease, angina, peripheral vascular disease, stroke, transient ischemic attack, or left ventricular dysfunction and congestive heart failure have a BP goal of <130/80mmHg.53 Thus, far more hypertensive African-Americans should have their BP lowered to <130/80mmHg.

Adherence and compliance concerns continue to be a major barrier in African-Americans to achieving excellent control. Aggressive management with strategic choices of combination therapy when BP is greater than 15/10mmHg above the goal BP seems the most appropriate approach to managing hypertension in uncomplicated African-American patients with moderate to severe stage 2 hypertension. However, in high-risk patients this approach is indicated even in stage 1 level hypertension since the goal is lower.

At the opposite end of the spectrum of BP is the pre-hypertensives group (BP 120–139/80–89mmHg). There are no databases with extensive longitudinal follow-up of African-Americans showing the rate of progression of BP elevation from pre-hypertension to hypertension. The Framingham data showed a four-year progression rate of 44% in individuals with BPs of 130–139/85–89mmHg, while the Trial of Preventing Hypertension (TROPHY) showed a rate of 63%, although both populations were primarily white.54,55 Nevertheless, NHANES cross-sectional data show a high prevalence of elevated BP at every age group in African-Americans and the BP level is higher within each class of BP in African-Americans. BP elevation and target organ damage occur earlier in African-Americans; therefore, the progression rate is most likely as high as in the TROPHY study, or perhaps even higher. Although the TROPHY study has shown that treatment in this range of BP is safe and well tolerated with an ARB, there are insufficient data to warrant treatment of all individuals in this range of pre-hypertensive BPs. Close follow-up of these individuals is the best approach to limit the early damage related to BP in African-Americans.

Summary

Improving BP management in African-Americans requires an approach that recognizes cultural, physiological, socioeconomic, and epidemiological differences compared with the general population of the US. In Jackson, MS, the Jackson Heart Project has documented better BP control rates in African-Americans than the national averages reported in NHANES.56 The AASK and ACCOMPLISH studies demonstrated that achieving BP control in African-Americans is clearly possible when adequate effort is applied. The medications available are successful and well tolerated. The following principles should be applied:

  • identify the BP goal for this patient by assessing overall risk;
  • define the BP reduction needed;
  • select drug treatment according to patient clinical profile;
  • consider the dose response for the medications according to that known for ethnic populations;
  • consider the socioeconomic, lifestyle and educational background of the patient in making drug choices; and
  • educate your patient on the disease, treatment expectations, and specific lifestyle modifications that are indicated.
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