Why do hypertensive patients of African ancestry respond better to calciumblockers and diuretics than to ACE inhibitors and β-adrenergic blockers? Asystematic review

Lizzy M Brewster; Yackoob K Seedat

doi:10.1186/1741-7015-11-141

Table 3 Summary of findings

From: Why do hypertensive patients of African ancestry respond better to calciumblockers and diuretics than to ACE inhibitors and β-adrenergic blockers? Asystematic review

Drug	High sodium diet	Pharmacokinetics	Pharmacodynamics
Ca-blockers	No effect* on BP lowering efficacy [34, 40, 41, 43]	1) Lower clearance nifedipine with African ancestry [46]	1) Ancestry/age profiling superior to renin in predictingdrug response [38]
		2) CYP3A4 genotypes sooner at BPgoal^†‡	2) Ca-blockers effectively block enhanced Ca-dependentvascular contractility, potentially mediated by high CK/lowNO with African ancestry (Figure 2) [11, 12, 72]
		3) CYP3A5 genotypes not associated with BP response [17, 24]	3) Pharmacogenomics: ACE G12269A, C17888T, andG20037A, and variants in the promoter region of theangiotensinogen gene (−217G = > A and–20A = > C), were not associated withBP response to respectively amlodipine and nifidipine [23, 26]
Diuretics	No effect on BP lowering efficacy [70]	No differences found between ancestry groups [33]	1) No association with plasma renin levels [57, 63, 65, 66], or ancestry/age better predictor of responsethan renin [15, 38]
			2) Diuretics effectively block enhanced sodium retention [86], potentially mediated by high CK in persons ofAfrican ancestry (Figure 3) [11, 12, 73, 87]
			3) Pharmacogenomics: greater BP response with AGT 6Aand AT1R 1166A alleles (only women); [30]GNB3T allele associated with greater BP response toHCT (only men); [32]ACE I/D, CYP11B2 C-344 T, RENA7174G [30], STK39[76], α-adducin Gly460Trp, ADRBK1, andGRK5 Gln41Leu [77] not associated with BP response
ACE-i	Lower efficacy with high salt [41]	No association of BP response with CYP3A4 A392G,T16090C, or CYP3A5 A6986G genotypes [17]	1) Ancestry/age profiling superior to renin in predictingdrug response [38]
			2) Low NO bioavailability may attenuate response(Figure 2) [10, 12, 36, 37, 72, 79–81]
			3) Pharmacogenomics: ACE DD poorer response to lisinopril;[28]^§ Homozygous ACE G12269A andC17888T faster on BP goal with ramipril than heterozygousgenotypes; [23] AA genotype 217G = > A and–20A= > C, promoter region of theangiotensinogen gene: no significant BP decrease withenalapril or lisinopril [26].
β-Blockers	No effect on BP lowering efficacy [70]	No consistent differences between persons of African vsEuropean ancestry [44, 45, 52, 55, 56, 59, 61, 64],[67]	1) Ancestry/age profiling superior to renin in predictingdrug response [15, 38, 53]
			2) High vascular contractility may promote peripheralvasoconstriction with β-adrenergic blockers(Figure 2) [3, 11, 12, 72, 88–92]
			3) Pharmacogenomics: ADRB1 Arg 389/Ser 49 associateswith greater, or attenuated BP lowering; [14, 20, 74]GRK4 Ala142Val faster on BP goal with metoprolol(only men); [19]GRK4 Arg65Leu and Ala486Val, GRK5 andGRK2 genotypes not associated with BP response [18, 77]

Legend: Diuretics, hydrochlorothiazide (HCT), or other diuretic drug;ACE-i, ACE inhibitors; β-blockers, β-adrenergi c blockers;BP, blood pressure; Ca-blockers, calcium channel blockers; CK,creatine kinase. *At higher drug dose;^†Pharmacodynamics unclear; ^‡Onlywomen/usual BP goal with CYP3A4 A392; or low BP goal withCYP3A4 16090C. ^§Very modest effect,−0.85 mm Hg systolic (SE 0.51) and −0.50 mm Hg diastolic(SE 0.28).

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