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

Abstract

BackgroundClinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy.MethodsUsing the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012.ResultsWe retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with 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 high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited.ConclusionAvailable data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy

“…12 Ethnic disparity in maternal and perinatal outcome in the general pregnant population is well described and likely to be multifactorial. 13 To our knowledge, no randomized controlled trials have investigated the impact of ethnicity on efficacy of antihypertensive treatment in pregnancy.…”

Antihypertensive drug therapy in patients with African ancestry

“…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 b-blockers, when used as monotherapy, is associated with poor BP-lowering effect [14].…”

“…However, in patients with African ancestry, these drug classes when used as monotherapy produce less BP-lowering effects [14]. Similarly, the use of b-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].…”

Is Creatine Kinase the Intrinsic Factor of Smooth Muscle Enhancing Vascular Contractility in Subjects of African Ancestry?

“…1 During the past 10 years, we have collected mounting evidence that vascular smooth muscle contractility of subjects of African ancestry is intrinsically enhanced, related to greater activity of the ATP-regenerating enzyme creatine kinase (CK). [2][3][4] The enzyme rapidly regenerates ATP near ATPases involved in smooth muscle contractility, including Ca 2+ ATPase and myosin ATPase. 2-4 α1-Adrenergic stimuli are reported to lead to enhanced vasoconstriction through Ca 2+ -dependent and Ca 2+ -independent pathways, including myosin light chain phosphorylation.…”

“…5 Greater activity of CK, as a possible final common pathway of vasoconstrictive responses, is thought to lead to enhanced agonistmediated vasoconstriction. [2][3][4] Importantly, contractility of human vessels ex vivo was found to be highly CK dependent, and CK inhibition led to a dose-dependent block of vasoconstriction on norepinephrine stimulation. 3 The ethnic difference in CK activity is less pronounced in women, 4 and this may explain the smaller differences in women found by Adefurin et al 1 Thus, consistent with the observations of Adefurin et al, 1 we propose that their data could be in part explained by enhanced venoconstriction in people of African ancestry as being attributable to greater CK activity in smooth muscle.…”