Expert Opinion on Pharmacotherapy
ISSN: 1465-6566 (Print) 1744-7666 (Online) Journal homepage: http://www.tandfonline.com/loi/ieop20
What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? Yackoob K Seedat MD PhD & Lizzy M Brewster MD PhD To cite this article: Yackoob K Seedat MD PhD & Lizzy M Brewster MD PhD (2014) What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?, Expert Opinion on Pharmacotherapy, 15:2, 159-161 To link to this article: http://dx.doi.org/10.1517/14656566.2014.857403
Published online: 12 Nov 2013.
Submit your article to this journal
Article views: 95
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ieop20 Download by: [109.161.198.106]
Date: 14 September 2015, At: 08:25
Editorial
What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? Yackoob K Seedat† & Lizzy M Brewster †
Downloaded by [109.161.198.106] at 08:25 14 September 2015
University of KwaZulu Natal, Nelson Mandela School of Medicine, Department of Medicine, Durban, South Africa
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 b-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to b-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 Expert Opin. Pharmacother. (2014) 15(2):159-161
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 b-adrenergic blockers are effective in Caucasians [4]. In a doubleblind 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 b-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 10.1517/14656566.2014.857403 © 2014 Informa UK, Ltd. ISSN 1465-6566, e-ISSN 1744-7666 All rights reserved: reproduction in whole or in part not permitted
159
Y. K. Seedat & L. Brewster
Table 1. Hypertension in blacks and whites biochemical differences [9]. Feature
In blacks
Downloaded by [109.161.198.106] at 08:25 14 September 2015
Total cholesterols Triglycerides High-density lipoproteins Low-density lipoproteins Very low density lipoproteins Response to Na+ load Urine Na+/K+ ratio Plasma Na+/K+ ratio Transport Quinidine Na+ pump activity
Lower Lower Higher Lower Lower Delayed Higher Higher High intracellular Na+ Reduced
Hypertension in blacks and whites hormonal differences Plasma renin activity Lower Plasma noradrenaline Equal Dopamine b-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 b-blockers b-blockers + thiazides a and b-blockers Methyldopa Vasodilators ACE inhibitors ACE inhibitors + thiazides Calcium channel blockers Angiotensin II antagonists
+ + + + + + + + + + +
++ + +/+ + + + +/+ + +/-
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 b-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
160
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]. 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 b-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 b-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 b-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 b-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.
Expert Opin. Pharmacother. (2014) 15(2)
African ancestry in hypertensive patients
Bibliography Papers of special note have been highlighted as either of interest () or of considerable interest () to readers. 1.
..
Downloaded by [109.161.198.106] at 08:25 14 September 2015
2.
3.
..
Opie LH, Seedat YK. Hypertension in sub-Saharan African populations. Circulation 2005;112:3562-08 A systematic overview of the etiology of hypertension and responses to antihypertensive drugs in sub-Saharan Africa, showing that differences with white populations are gradual and overlapping. Ford ES. Trends in mortality from all causes and cardiovascular disease among hypertensives and nonhypertensives adults in the United States. Circulation 2011;123:1737-44 Brewster LM, van Montfrans GA, Kleijnen J. Systematic review: antihypertensive drug therapy in black patients. Ann intern Med 2004;141:614-27 Systematic review of randomized controlled trials of antihypertensive drugs in patients of African ancestry, confirming clinical impressions of lesser efficacy of ACEi/ARB and beta-adrenergic blockers, but showing similar clinical outcomes when drugs are combined.
4.
Prichard BNC, Gillam PMS. Treatment of hypertension with propranolol. Br Med J 1969;1:7-16
5.
Humphreys GS, Delvin DG. Ineffectiveness of propranolol in
.
hypertensive Jamaicans. Br Med J 1968;2:601-3 One of the first accounts of a different efficacy of antihypertensive drugs in patients of African ancestry, showing propranolol was less effective.
6.
Grell GAC. Propanolol in black hypertensives. Br Med J 1978;2:358
7.
Seedat YK. Propanolol in the South African non-white hypertensive patient. S Afr Med J 1971;45:284-5
8.
Seedat YK. Trial of atenolol and chlorthalidone for hypertension in black South Africans. Br Med J 1980;281:1241-7
9.
Seedat YK. Hypertension in developing nations in sub-Saharan Africa. J Human Hypertension 2000;14:739-47 Landmark paper that foresees a wave of cardiovascular disease of epidemic proportions to come to sub-Saharan Africa in the coming decades, and proposes appropriate measures for detection and management of risk factors to meet this emerging challenge.
..
10.
Seedat YK, Rayner BL. South African hypertension guideline 2011. S Afr Med J 2012;102:57-84
11.
Brewster LM, Seedat YK. Why do hypertensive patients of African ancestry respond better to calcium channel and diuretics than to ACE inhibitors and
Expert Opin. Pharmacother. (2014) 15(2)
..
12.
.
beta-adrenergic blockers? A systematic review. BMC Med 2013;11:141 A systematic exploration of environmental, pharmacokinetic, pharmacodynamic and pharmacogenomic factors that may explain the differential response of patients of African ancestry to antihypertensive drugs, showing selfdefined African ancestry is the best available predictor of this differential response. Flack JM, Sica DA, Bakris G, et al. Management of high blood pressure in Blacks. An update of the International Society of Hypertension in Blacks consensus statement. Hypertension 2010;56:780-800 The most extensive guideline on hypertension treatment in persons of African ancestry.
Affiliation
Yackoob K Seedat†1 MD PhD & Lizzy M Brewster2 MD PhD † Author for correspondence 1 Emeritus Professor of Medicine, University of KwaZulu Natal, Nelson Mandela School of Medicine, Department of Medicine, Private Bag 7, Congella 4013, Durban, South Africa E-mail: [email protected] 2 Senior Staff Physician, Departments of Internal and Vascular Medicine, F4-222, Academic Medical Centre, Meibergdreef 9,1105 AZ Amsterdam, The Netherlands
161
ISSN: 1465-6566 (Print) 1744-7666 (Online) Journal homepage: http://www.tandfonline.com/loi/ieop20
What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? Yackoob K Seedat MD PhD & Lizzy M Brewster MD PhD To cite this article: Yackoob K Seedat MD PhD & Lizzy M Brewster MD PhD (2014) What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?, Expert Opinion on Pharmacotherapy, 15:2, 159-161 To link to this article: http://dx.doi.org/10.1517/14656566.2014.857403
Published online: 12 Nov 2013.
Submit your article to this journal
Article views: 95
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ieop20 Download by: [109.161.198.106]
Date: 14 September 2015, At: 08:25
Editorial
What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? Yackoob K Seedat† & Lizzy M Brewster †
Downloaded by [109.161.198.106] at 08:25 14 September 2015
University of KwaZulu Natal, Nelson Mandela School of Medicine, Department of Medicine, Durban, South Africa
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 b-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to b-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 Expert Opin. Pharmacother. (2014) 15(2):159-161
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 b-adrenergic blockers are effective in Caucasians [4]. In a doubleblind 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 b-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 10.1517/14656566.2014.857403 © 2014 Informa UK, Ltd. ISSN 1465-6566, e-ISSN 1744-7666 All rights reserved: reproduction in whole or in part not permitted
159
Y. K. Seedat & L. Brewster
Table 1. Hypertension in blacks and whites biochemical differences [9]. Feature
In blacks
Downloaded by [109.161.198.106] at 08:25 14 September 2015
Total cholesterols Triglycerides High-density lipoproteins Low-density lipoproteins Very low density lipoproteins Response to Na+ load Urine Na+/K+ ratio Plasma Na+/K+ ratio Transport Quinidine Na+ pump activity
Lower Lower Higher Lower Lower Delayed Higher Higher High intracellular Na+ Reduced
Hypertension in blacks and whites hormonal differences Plasma renin activity Lower Plasma noradrenaline Equal Dopamine b-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 b-blockers b-blockers + thiazides a and b-blockers Methyldopa Vasodilators ACE inhibitors ACE inhibitors + thiazides Calcium channel blockers Angiotensin II antagonists
+ + + + + + + + + + +
++ + +/+ + + + +/+ + +/-
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 b-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
160
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]. 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 b-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 b-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 b-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 b-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.
Expert Opin. Pharmacother. (2014) 15(2)
African ancestry in hypertensive patients
Bibliography Papers of special note have been highlighted as either of interest () or of considerable interest () to readers. 1.
..
Downloaded by [109.161.198.106] at 08:25 14 September 2015
2.
3.
..
Opie LH, Seedat YK. Hypertension in sub-Saharan African populations. Circulation 2005;112:3562-08 A systematic overview of the etiology of hypertension and responses to antihypertensive drugs in sub-Saharan Africa, showing that differences with white populations are gradual and overlapping. Ford ES. Trends in mortality from all causes and cardiovascular disease among hypertensives and nonhypertensives adults in the United States. Circulation 2011;123:1737-44 Brewster LM, van Montfrans GA, Kleijnen J. Systematic review: antihypertensive drug therapy in black patients. Ann intern Med 2004;141:614-27 Systematic review of randomized controlled trials of antihypertensive drugs in patients of African ancestry, confirming clinical impressions of lesser efficacy of ACEi/ARB and beta-adrenergic blockers, but showing similar clinical outcomes when drugs are combined.
4.
Prichard BNC, Gillam PMS. Treatment of hypertension with propranolol. Br Med J 1969;1:7-16
5.
Humphreys GS, Delvin DG. Ineffectiveness of propranolol in
.
hypertensive Jamaicans. Br Med J 1968;2:601-3 One of the first accounts of a different efficacy of antihypertensive drugs in patients of African ancestry, showing propranolol was less effective.
6.
Grell GAC. Propanolol in black hypertensives. Br Med J 1978;2:358
7.
Seedat YK. Propanolol in the South African non-white hypertensive patient. S Afr Med J 1971;45:284-5
8.
Seedat YK. Trial of atenolol and chlorthalidone for hypertension in black South Africans. Br Med J 1980;281:1241-7
9.
Seedat YK. Hypertension in developing nations in sub-Saharan Africa. J Human Hypertension 2000;14:739-47 Landmark paper that foresees a wave of cardiovascular disease of epidemic proportions to come to sub-Saharan Africa in the coming decades, and proposes appropriate measures for detection and management of risk factors to meet this emerging challenge.
..
10.
Seedat YK, Rayner BL. South African hypertension guideline 2011. S Afr Med J 2012;102:57-84
11.
Brewster LM, Seedat YK. Why do hypertensive patients of African ancestry respond better to calcium channel and diuretics than to ACE inhibitors and
Expert Opin. Pharmacother. (2014) 15(2)
..
12.
.
beta-adrenergic blockers? A systematic review. BMC Med 2013;11:141 A systematic exploration of environmental, pharmacokinetic, pharmacodynamic and pharmacogenomic factors that may explain the differential response of patients of African ancestry to antihypertensive drugs, showing selfdefined African ancestry is the best available predictor of this differential response. Flack JM, Sica DA, Bakris G, et al. Management of high blood pressure in Blacks. An update of the International Society of Hypertension in Blacks consensus statement. Hypertension 2010;56:780-800 The most extensive guideline on hypertension treatment in persons of African ancestry.
Affiliation
Yackoob K Seedat†1 MD PhD & Lizzy M Brewster2 MD PhD † Author for correspondence 1 Emeritus Professor of Medicine, University of KwaZulu Natal, Nelson Mandela School of Medicine, Department of Medicine, Private Bag 7, Congella 4013, Durban, South Africa E-mail: [email protected] 2 Senior Staff Physician, Departments of Internal and Vascular Medicine, F4-222, Academic Medical Centre, Meibergdreef 9,1105 AZ Amsterdam, The Netherlands
161
