Antihypertensive drug therapy in patients with African ancestry

Abstract

Blood pressure plays an important role in the development and progression of cardiovascular disease. Among hypertensive patients, those with African ancestry present with distinctive metabolic characteristics and cardiovascular profile. As a result, the need for individualized antihypertensive treatment strategy is of great importance. Lifestyle modifications as well as low sodium diet will play a major role in controlling blood pressure. The initiation of antihypertensive treatment with calcium channel blockers or diuretics is favored over angiotensin receptor blockers, angiotensin-converting enzyme inhibitors or β-blockers, provided no specific indications for the latter drugs are present. Moreover, the need for combination treatment often arises. As a result, the effective and safe hypertension management of patients with African ancestry is of critical importance for reducing cardiovascular morbidity and mortality.

Keywords::

• African ancestry
• antihypertensive drugs
• hypertension

1. Introduction

Hypertension is among the key factors responsible for cardiovascular disease (CVD) development and progression. Furthermore, the prevalence of hypertensive patients is continuously increasing [1]. Moreover, despite the wide range of blood pressure (BP)-lowering agents, satisfactory control of hypertension is often difficult to achieve. As a result, the need for an effective treatment plan in order to achieve optimal BP control is of critical importance.

Some subgroups of patients have unique characteristics that require a different approach compared with the general population when designing the antihypertensive treatment plan. Patients with African ancestry are such an example of a distinctive subgroup of patients. Indeed, the metabolic characteristics of black patients contribute to an increased severity of hypertension complications, as well as a different response of black patients to antihypertensive treatment.

2. Hypertension in patients with African ancestry

Hypertensive patients with African ancestry often present with additional coexisting cardiovascular risk factors and have increased severity of some complications of hypertension. Indeed, African ancestry patients have increased prevalence of obesity, which is associated with increased hypertension prevalence and hypertensive complications [2]. Moreover, they have increased salt sensitivity [3]. Furthermore, microvascular and macrovascular structural and functional abnormalities are often of increased severity in black patients with excessive target organ damage [3].

The state of the renin–angiotensin–aldosterone system (RAAS) system in subjects of African ancestry is poorly understood [4]. Black patients have low renin activity [5] coupled with lower aldosterone [6]. On the other hand, there is an excessive RAAS system-dependent target organ damage in black hypertensive patients. The mechanisms by which a low-renin state can be associated with such an apparently active RAAS are not clear.

Subjects with African ancestry have an increased prevalence as well as early onset of hypertension [3]. Furthermore, this subgroup of hypertensive patients often has poor BP control [7]. In addition, the prevalence of resistant hypertension is greater in patients with African ancestry than whites [3]. Furthermore, black patients have smaller night dip in systolic blood pressure (SBP) [8]. As a result, an increased CVD prevalence and mortality associated with hypertension is observed in patients with African ancestry [9].

Using data from the Atherosclerosis Risk in Communities (ARIC) study, it was shown that African-Americans have an increased incidence of unprovoked hypokalemia (odds ratio = 5.3; 95% CI: 3.6 – 7.7) [10]. This was more than five times higher compared with European Americans. As a result, a careful assessment and follow-up is important after the initiation of an antihypertensive treatment that may affect potassium levels. Moreover, patients with African ancestry have increased risk for angiotensin-converting enzyme inhibitor (ACE-I)-associated angioedema [11] and cough [12]. Therefore, careful monitoring of these patients is required when prescribing an ACE-I.

3. Antihypertensive treatment

At the cornerstone of an effective BP control treatment and CVD risk management is the change in lifestyle and diet. This holds true for the general population but is even more important regarding patients with African ancestry. Indeed, it has been shown that hypertensive African-American patients benefited more from a low sodium dietary intervention in accordance with the Dietary Approaches to Stop Hypertension (DASH) diet [13].

Among the various antihypertensive drug classes, angiotensin receptor blockers (ARBs) as well as ACE-Is have established efficacy as well as safety. As a result, they are commonly used as the starting treatment for hypertension and often as monotherapy. However, in patients with African ancestry, these drug classes when used as monotherapy produce less BP-lowering effects [14]. Similarly, the use of β-blockers, when used as monotherapy, is associated with poor BP-lowering effect [14]. In contrast, thiazide diuretics and calcium channel blockers (CCBs) have proven more effective when started as monotherapy in African ancestry patients [15]. However, black patients will often require a combination therapy to achieve satisfactory BP control. The combination of an ARB, ACE-I, or β-blocker with a diuretic or a CCB is expected to produce an important BP-lowering effect.

Of note, the African American Study of Kidney Disease and Hypertension showed that ACE-Is were more effective than β-blockers or dihydropyridine CCBs in slowing renal function decline in African-Americans with established hypertensive renal disease [16]. Moreover, the use of β-blockers in black patients has been associated with improved outcomes in both patients with a history of myocardial infarction as well as patients with heart failure [17,18]. As a result, when there is an indication for prescribing a specific antihypertensive drug category, such as a β-blocker or an ACE-I, these drug classes should be preferred even as monotherapy.

The International Society on Hypertension in Blacks (ISHIB) has issued a consensus statement regarding the management of high BP in black patients [3]. For hypertensive patients with African ancestry without target organ damage, preclinical CVD, or overt CVD, a target BP lower than 135/85 mmHg is recommended. On the other hand, black patients with target organ damage, preclinical CVD, and/or a history of CVD, a target BP lower than 130/80 mmHg is recommended. When baseline BP is 10/5 mmHg higher than the target levels, monotherapy with a diuretic or CCB is recommended. In cases where BP is 15/10 mmHg above target, combination therapy is suggested with either a CCB plus an acting drug on the renin–angiotensin system (RAS) or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a RAS acting drug.

Recently, the evidence-based guideline for the management of high BP in adults report from the panel members appointed to the eighth Joint National Committee (JNC 8) has been published [19]. Based on the JNC 8 recommendations, in the general population older than 60 years old, BP should be treated to a goal SBP < 150 mmHg and goal diastolic blood pressure (DBP) < 90 mmHg. However, as an expert opinion of the JNC 8, if pharmacological treatment for high BP results in lower achieved SBP (e.g., < 140 mmHg) in the latter population and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. On the other hand, in patients younger than 60 years old, diabetic patients and patients with chronic kidney disease (CKD) with or without diabetes BP should be treated to a goal SBP < 140 mmHg and goal DBP < 90 mmHg. Regarding black patients, the initial antihypertensive treatment should include a thiazide-type diuretic or a CCB and if not adequate BP control is achieved, the addition of an ACE-I or ARB is recommended. Of note, regarding black patients with CKD and proteinuria, an ACE-I or ARB is recommended as initial therapy because of the higher likelihood of progression of renal disease. In black patients with CKD but without proteinuria, the choice for initial therapy is less clear and includes a thiazide-type diuretic, CCB, ACE-I, or ARB. If an ACE-I or ARB is not used as the initial drug, then an ACE-I or ARB can be added as a second-line drug if necessary to achieve goal BP.

The guidelines from the ISHIB propose a lower BP goal compared with those from the JNC. This in part is based on the higher CVD risk of black patients. It has been shown that young African-American men, despite comparable brachial BP, had greater central BP compared with young white men, a difference that was reflected upon a greater macrovascular and microvascular dysfunction present in these apparently healthy African-American men [20]. Furthermore, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the chlorthalidone group, in which BP averaged 134/76 mmHg at 4.9-year follow-up, had better CVD outcomes, particularly among black participants, compared with the other treatment groups that had less-effective BP control [21]. The Cardio-Sis study was a prospective, randomized trial in 1111 European nondiabetic men and women with SBP ≥ 150 mmHg, average age 67 years, plus one additional CVD risk factor at entry [22]. The study compared the target SBP of < 140 mmHg (usual control; n = 553) or < 130 mmHg (tight control). After a median 2-year follow-up, the rate of electrocardiographic left ventricular hypertrophy (primary end point) was 37% lower (p = 0.013) in the tight control group compared with the usual control group. The secondary composite CVD end point was also lower (9.4 vs 4.8%; p = 0.003) in the tight control group. The attained BP level at the end of 2-year follow-up was 131.9/74.0 in the tight control group versus 135.6/78.7 mmHg in the usual control group (72.2 vs 27.3% achieved BP 130/80 mmHg).

However, there are not many clinical trials evaluating this lower BP goal, especially in patients with African ancestry. As a result, this key question of BP goal in clinical hypertension management remains to be answered by future clinical studies. On the other hand, since black patients with hypertension have been shown to have a disproportionate degree of CVD risk and target organ damage compared with white patients of similar BP, it is clinically reasonable to suggest a lower BP target.

4. Expert opinion

Hypertensive patients with African ancestry are a distinctive subgroup of patients that presents with some unique characteristics. These patients commonly have increased incidence and early onset of hypertension and often poor BP control. Moreover, they exhibit increased salt sensitivity, as well as endothelial dysfunction. In addition, they often present with additional concomitant CVD risk factors. As a result, they have increased CVD risk and require a careful and comprehensive antihypertensive management.

Antihypertensive treatment should start, as with all hypertensive patients, with appropriate lifestyle changes accompanied by low sodium DASH diet. A diuretic or CCB is a reasonable choice for the first-line treatment of hypertension in black patients. However, patients of this subgroup will often require a combination drug therapy. An ARB or an ACE-I can be used as the second-line antihypertensive drug that can be added on top of the baseline treatment. Of note, in cases where there is a clear indication based on the patient’s medical background for the prescription of specific BP-lowering drug category, it should be given even as first-line antihypertensive drug. In addition, the patient’s age should also be considered when selecting an antihypertensive treatment [23,24]. Indeed, queries are raised regarding the metabolic profile as well as other adverse effects when prescribing a member of the diuretic class in younger patients. This is also a concern in older people, but diuretics should only be considered as a first-line monotherapy in this group, particularly with early heart failure present.

Although there is a growing body of clinical evidence regarding the management of hypertension in patients with African ancestry, additional research is needed to identify effective treatment strategies and target goals for the management of hypertension. These individualized interventions will contribute to a decrease in CVD development and progression in a population subgroup already at high CVD risk.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.