What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

Abstract

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit.

Keywords::

• African ancestry
• antihypertensive drugs

The background of hypertension in populations of African ancestry is that the disorder in these patients is often more severe, more resistant to treatment and leads to earlier organ damage and premature death. Hypertension appears to be a more aggressive disease and malignant-accelerated hypertension is more severe in those of African ancestry compared to Caucasians [1,2]. This has important implications for the choice of antihypertensive agents [3]. The African ancestry population in sub-Saharan Africa consist of about 1 billion people and the average income per person is about 1 – 2 US $ per day. The African diaspora extend to the USA, South America mainly in Brazil, West Indies and to lesser extent the UK and Europe. In the USA, the average income of the Caucasians is twice as high as those of African ancestry.

Historically β-adrenergic blockers are effective in Caucasians [4]. In a double-blind cross-over trial on 18 hypertensive Jamaicans, however, Humphreys and Delvin found no significant difference between propranolol and an inert placebo [5]. This was not reported by Grell in an open study of the drug [6]. Control of blood pressure with propranolol was reported in 8 out of 12 Indians and only 4 out of 13 black hypertensive patients [7]. The lowering in blood pressure in the Indians was statistically significant (p ≤ 0.002). Subsequently, one of us (YKS), did a study in 24 black patients (Zulus) in a double-blind, placebo-controlled cross-over trial of the efficacy of a β-adrenergic agent (atenolol) 100 mg once daily as compared with chlorthalidone 25 mg once daily. The two drugs were also given combined at these doses and the effects were compared with those of the drugs given alone. Atenolol as sole drug treatment had no appreciable effect on blood pressure as compared to placebo. Chlorthalidone produced a small decrease, but this was statistically significant. Combining the two drugs, however, produced a significant reduction in blood pressure (mean lying blood pressure p ≤ 001); mean standing blood pressure p ≤ 0002 [8]. These findings suggest that β-adrenergic blockers should not be regarded as baseline treatment of hypertension [7,8].

The determinant factors of hypertension show that there are important differences in those of African ancestry and Caucasian subjects. These are summarised in Table 1 [9]. The antihypertensive agents in the African ancestry and Caucasian groups are shown in Table 2 [9].

Table 1. Hypertension in blacks and whites biochemical differences [9].

Feature	In blacks
Total cholesterols	Lower
Triglycerides	Lower
High-density lipoproteins	Higher
Low-density lipoproteins	Lower
Very low density lipoproteins	Lower
Response to Na^+ load	Delayed
Urine Na^+/K^+ ratio	Higher
Plasma Na^+/K^+ ratio	Higher
Transport	High intracellular Na^+
Quinidine Na^+ pump activity	Reduced
Hypertension in blacks and whites hormonal differences
Plasma renin activity	Lower
Plasma noradrenaline	Equal
Dopamine β-hydroxylase	Lower
Aldosterone	Higher
Kallikrein	Lower
Circulating inhibition of Na/K ATPase	Higher

Table 2. Antihypertensive agents in white and black communities [9].

Agent	White	Black
Thiazide	+	++
Rauwolfia	+	+
β-blockers	+	+/−
β-blockers + thiazides	+	+
α and β-blockers	+	+
Methyldopa	+	+
Vasodilators	+	+
ACE inhibitors	+	+/−
ACE inhibitors + thiazides	+	+
Calcium channel blockers	+	+
Angiotensin II antagonists	+	+/−

Clinicians are encouraged to take an individualised approach. Patients of African ancestry as a group respond better when treating hypertension to calcium channel blocker (CCB) and a thiazide like diuretic or indapamide, while the response to β-adrenergic blocker or angiotensin converting enzyme inhibitor (ACEI) is attenuated [3,10]. This pertains to monotherapy in patients of African ancestry. As yet there is no ideal antihypertensive agent which may be used in patients of African ancestry. In addition ACEI or β-adrenergic blockers produce the same antihypertensive effect as CCB if it is combined with a thiazide like diuretic or indapamide (Table 2) [9]. Only about 30% of patients respond initially to monotherapy and the trend in the treatment of hypertension is to resort to polytherapy if the initial BP is ≥ 20/10 mmHg above target goals for either systolic or diastolic levels [10]. An ideal antihypertensive agent should not only have natriuretic effect but also in patients of African ancestry capable of lowering vascular resistance.

We retrieved 3763 articles and 72 reports that consisted mainly the four major classes of antihypertensive drugs, CCB and thiazide like diuretics or indapamide, drugs that block the renin–angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and creatine kinase may explain individual response but clinical data are very limited. African ancestry seems to be the best predictor of individual responses to antihypertensive drug [11].

In conclusion, we should be aware of the special African ancestry when initiating treatment with monotherapy. Guidelines for the treatment of patients of African ancestry have recognised this important fact [10,12]. It is probable that with the concept of prescribing polytherapy ab initio a two drug combination should the BP be ≥ 20/10 mm Hg above treatment goals should obviate the problem. (Table 2 ) [10]. A thiazide like drug if it has not been in the individual patient as a first line drug is a useful combination with either a β-blocker or an ACEI or angiotensin reccptor blocker.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.