***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND African Americans have a disproportionate burden of hypertension and comorbid disease . Pharmacogenetic markers of blood pressure response have yet to be defined clearly . This study explores the association between G-protein-coupled receptor kinase type 4 ( GRK4 ) variants and blood pressure response to metoprolol among African Americans with early hypertensive nephrosclerosis . METHODS Participants from the African American Study of Kidney Disease and Hypertension ( AASK ) trial were genotyped at three GRK4 polymorphisms : R65L , A142V , and A486V . A Cox proportional hazards model , stratified by gender , was used to determine the relationship between GRK4 variants and time to reach a mean arterial pressure ( MAP ) of 107 mm Hg , adjusted for other predictors of blood pressure response . Potential interactions between the three polymorphisms were explored by analyzing the effects of gene haplotypes and by stratifying the analysis by neighboring sites . RESULTS The hazard ratio with 95 % confidence interval by A142V among men r and omized to a usual MAP ( 102 - 107 mm Hg ) was 1.54 ( 1.11 - 2.44 ; P = 0.0009 ) . The hazard ratio by A142V with R65/L65 or L65/L65 was 2.14 ( 1.35 - 3.39 ; P = 0.001 ) . Haplotype analyses were consistent but inconclusive . There was no association between A142V and blood pressure response among women . CONCLUSIONS Results suggest a sex-specific relationship between GRK4 A142V and blood pressure response among African-American men with early hypertensive nephrosclerosis . Men with a GRK4 A142 were less responsive to metoprolol if they had a GRK4 L65 variant . The effect of GRK4 variants and blood pressure response to metoprolol should be studied in larger clinical trials A single-blind , placebo-controlled study was conducted to compare the inhibitory effects of intravenous propranolol on  exercise-induced tachycardia in eight matched pairs of healthy black and white volunteers , consisting of equal numbers of men and women . At the beginning of each test session , subjects were exercised on a bicycle ergometer -- the load predetermined to increase their heart rates to 160 - 190 beats/min . Exactly 30 min after having received an intravenous injection of placebo or propranolol ( the dose varying from 0.0125 to 0.15 mg/kg ) , they were subjected to the same exercise load . Heart rates were continuously recorded throughout exercise periods , and readings at 6 , 8 , and 10 min were compared for pre- and postinjection periods . A washout period of at least 3 days was allowed to elapse between sessions . Postinjection reductions of heart rate in blacks were compared with postinjection reductions in their white counterparts . Analysis of results indicated that the dose-response curve for the heart rate reduction result ing from propranolol for blacks was shifted to the right with respect to that for whites . In clinical terms , this means that to achieve the same degree of beta-blockade in blacks , a larger dose of propranolol is required than for whites , but that the same maximum is attainable In a double-blind , outcome trial conducted in hypertensive patients r and omized to chlorthalidone ( C ) , amlodipine ( A ) , lisinopril ( L ) , or doxazosin ( D ) , the α-adducin Gly460Trp polymorphism was typed ( n=36 913 ) . Mean follow-up was 4.9 years . Relative risks ( RRs ) of chlorthalidone versus other treatments were compared between genotypes ( Gly/Gly+Gly/Trp versus Trp/Trp ) . Primary outcome was coronary heart disease ( CHD ) . Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype ( P=0.660 ) . Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women ( RR=1.31 ) but not men ( RR=0.91 ) with no RR gender differences for non-carriers ( gender – gene – treatment interaction , P=0.002 ) . The α-adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk , but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implication s for hypertension treatment Purpose : To explore the association between CYP3A4 and CYP3A5 gene polymorphisms and blood pressure response to amlodipine  among participants from the African-American Study of Kidney Disease and Hypertension Trial r and omized to amlodipine ( n = 164 ) . Methods : Cox proportional hazards models were used to determine the risk of reaching a target mean arterial pressure ( MAP ) of ≤107 mm Hg by CYP3A4 ( A–392 G and T16090C ) and CYP3A5 ( A6986 G ) gene polymorphisms , stratified by MAP r and omization group ( low or usual ) and controlling for other predictors for blood pressure response . Results : Women r and omized to a usual MAP goal with an A allele at CYP3A4 A–392 G were more likely to reach a target MAP of 107 mm Hg . The adjusted hazard ratio ( AA/AG compared to GG ) with 95 % confidence interval was 3.41 ( 1.20–9.64 ; p = 0.020 ) . Among participants r and omized to a lower MAP goal , those with the C allele at CYP3A4 T16090C were more likely to reach target MAP : The adjusted hazard ratio was 2.04 ( 1.17–3.56 ; p = 0.010 ) . After adjustment for multiple testing using a threshold significance level of p = 0.016 , only the CYP3A4 T16090C SNP remained significant . CYP3A5 A6986 G was not associated with blood pressure response . Conclusions : Our findings suggest that blood pressure response  to amlodipine among high-risk African-Americans appears to be determined by CYP3A4 genotypes , and sex specificity may be an important consideration . Clinical applications of CYP3A4 genotype testing for individualized treatment regimens warrant further study OBJECTIVES The purpose of this study was to evaluate the efficacy and tolerability of monotherapy with the selective aldosterone blocker eplerenone in both black and white patients with hypertension . BACKGROUND Essential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S. METHODS Black ( n = 348 ) and white ( n = 203 ) patients with mild-to-moderate hypertension were r and omized to double-blind treatment with eplerenone 50 mg , the angiotensin II receptor antagonist losartan 50 mg , or placebo once daily . Doses were increased if blood pressure remained uncontrolled . The primary end point was change in mean diastolic blood pressure ( DBP ) after 16 weeks of therapy . RESULTS Adjusted mean changes from baseline in DBP were -5.3 + /- 0.7 , -10.3 + /- 0.7 , and -6.9 + /- 0.6 mm Hg in the placebo , eplerenone-treated , and losartan-treated groups , respectively ( mean + /- SE , p < 0.001 eplerenone vs. placebo , p < 0.001 eplerenone vs. losartan ) . In black patients , DBP decreased by -4.8 + /- 1.0 , -10.2 + /- 0.9 , and -6.0 + /- 0.9 mm Hg for the placebo , eplerenone-treated , and losartan-treated groups , respectively ( mean + /- SE , p < 0.001 eplerenone vs. placebo , p < 0.001 eplerenone vs. losartan ) , whereas in white patients , DBP decreased by -6.4 + /- 1.0 , -11.1 + /- 1.1 , and -8.4 + /- 1.0 mm Hg , respectively ( p = 0.001 eplerenone vs. placebo , p = 0.068 for eplerenone vs. losartan ) . For reduction of systolic blood pressure ( SBP ) , eplerenone was superior to placebo and losartan in all patients combined and in black patients , and was superior to placebo in white patients . Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient , but more effective than losartan in the low renin patient . Similarly , eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone . Both eplerenone and losartan were well tolerated . CONCLUSIONS The antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients Background — We previously hypothesized that high activity of creatine kinase , the central regulatory enzyme of energy metabolism , facilitates the development of high blood pressure . Creatine kinase rapidly provides adenosine triphosphate to highly energy-dem and ing processes , including cardiovascular contraction , and antagonizes nitric oxide – mediated functions . Relatively high activity of the enzyme , particularly in resistance arteries , is thought to enhance pressor responses and increase blood pressure . Tissue creatine kinase activity is reported to be high in black people , a population subgroup with greater hypertension risk ; the proposed effects of high creatine kinase activity , however , are not “ race dependent . ” We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population . Methods and Results — We analyzed a stratified r and om sample of the population of Amsterdam , the Netherl and s , consisting of 1444 citizens ( 503 white European , 292 South Asian , 580 black , and 69 of other ethnicity ) aged 34 to 60 years . We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest , as a substitute measure of tissue activity . Creatine kinase was independently associated with blood pressure , with an increase in systolic and diastolic pressure , respectively , of 8.0 ( 95 % CI , 3.3 to 12.7 ) and 4.7 ( 95 % CI , 1.9 to 7.5 ) mm Hg per log creatine kinase increase after adjustment for age , sex , body mass index , and ethnicity . Conclusions — Creatine kinase is associated with blood pressure . Further studies are needed to explore the nature of this association , including how variation in cardiovascular creatine kinase activity may affect pressor responses Objectives In the vast majority of cases the cause for hypertension is not known . On the basis of observations from black and multiethnic population s , it has been hypothesized that a genetically high tissue creatine kinase activity may be an independent factor responsible for primary hypertension . If the relation between creatine kinase and blood pressure is causal , it is reasonable to believe that it will be independent of ethnicity and present in different population s. In this cross-sectional study , we examined whether creatine kinase was associated with blood pressure in a large Caucasian normal population . Methods and results Data on  creatine kinase and blood pressure were analyzed in a r and om sample of 12 776 men and women ( 65 % of those eligible ) , aged 30–87 years from a normal population in the municipality of Tromsø , Norway . We used linear regression to model the association between  creatine kinase and blood pressure .  Creatine kinase was independently associated with blood pressure . A one unit increase in log CK was associated with a 3.3 ( 95 % CI 1.4–5.2 ) mmHg increase in systolic blood pressure and a 1.3 ( 95 % CI 0.3–2.3 ) mmHg increase in diastolic blood pressure , after adjustment for age , sex , body mass index , s-glucose , s-creatinine , physical activity and alcohol consumption . The creatine kinase effect on blood pressure was independent of antihypertensive medication , and no difference in creatine kinase level was found between those with controlled and uncontrolled hypertension ( geometric mean 101 vs. 104 IU/l , P = 0.1 ) . Conclusion Creatine kinase was associated with blood pressure in this population BACKGROUND Age and race categories or renin profiling have been recommended to predict blood pressure responses to monotherapy with a beta-blocker or thiazide diuretic . Whether these or other characteristics predict blood pressure responses when the drugs are administered as add-on therapy is uncertain . METHODS We evaluated predictors of blood pressure response in 363 men and women < or = 65 years of age with primary hypertension ( 152 blacks , 211 whites ) , 86 of whom ( 24 % ) were untreated and 277 of whom ( 76 % ) were withdrawn from previous antihypertensive drugs before r and omization to either atenolol followed by addition of hydrochlorothiazide ( N = 180 ) or hydrochlorothiazide followed by addition of atenolol ( N = 183 ) . Responses were determined by home blood pressure averages before and after each drug administration . Race , age , plasma renin activity , and other characteristics including pretreatment blood pressure levels were incorporated into linear 
    Output:
    
Pharmacokinetics , plasma renin and genetic polymorphisms did notwell predict the response of patients of African ancestry toantihypertensive drugs .
Conclusion Available data are inconclusive regarding why patients of African ancestrydisplay the typical response to antihypertensive drugs .
In lieu ofbiochemical or pharmacogenomic parameters , self-defined African ancestryseems the best available predictor of individual responses toantihypertensive drugs