***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND The African American Study of Kidney Disease and Hypertension ( AASK ) is an ongoing trial to evaluate the effect of blood pressure and choice of antihypertensive drug on the rate of decline of renal function . OBJECTIVE To present the success of the AASK in achieving the trial 's rigorous blood pressure goals in an extremely challenging patient population . METHODS The AASK participants included African American patients with hypertension ( n = 1094 ) , aged 18 to 70 years , with glomerular filtration rates between 20 and 65 mL/min per 1.73 m(2 ) and no other identified causes of renal insufficiency . Participants were r and omized to a goal mean  arterial blood pressure  ( MAP ) of either 102 to 107 mm Hg ( usual MAP goal ) or 92 mm Hg or less ( low MAP goal ) . Participants in each of these groups were also r and omized ( double-blind ) to a regimen containing metoprolol succinate , ramipril , or amlodipine besylate . Additional agents were added , if required , in the following recommended order : furosemide , doxazosin mesylate , clonidine hydrochloride , or hydralazine hydrochloride ( or minoxidil , if needed ) . RESULTS In participants r and omized to the low MAP goal , the percentage of participants who achieved a blood pressure of less than 140/90 mm Hg increased from a baseline of 20.0 % to 78.9 % by 14 months after r and omization . For usual MAP goal participants , the corresponding percentages increased from 21.5 % to 41.8 % . The difference in median levels of MAP between the 2 MAP goal groups increased and remained at approximately 12 mm Hg . Blood pressure reduction was similar regardless of age , sex , body mass index , education , insurance or employment status , income , or marital status . CONCLUSION The blood pressure goals set and achieved in AASK participants clearly demonstrate that adequate blood pressure control can be achieved even in hypertensive population s whose blood pressure is the most difficult to control Abstract —The genes of the renin-angiotensin system have been subjected to intense molecular scrutiny in cardiovascular disease studies , but their contribution to risk is still uncertain . In this study , we sample d 192 African American and 153 European American families ( 602 and 608 individuals , respectively ) to evaluate the contribution of variations in genes that encode renin-angiotensin system components of susceptibility to hypertension . We genotyped 25 single-nucleotide polymorphisms in the renin-angiotensin system genes ACE , AGT , AGTR1 , and REN . The family-based transmission/disequilibrium test was performed with each single-nucleotide polymorphism and with the multilocus haplotypes . Two individual single-nucleotide polymorphisms were significantly associated with  hypertension among African Americans , and this result persisted when both groups were combined . The associations were confirmed in haplotype analysis for REN , AGTR1 , and ACE in African Americans . Consistent but less significant evidence was found in European Americans . We also r and omly sample d unrelated individuals across families to obtain 84 cases and 108 controls among the African Americans and 41 cases and 113 controls in the European Americans .  Single-nucleotide polymorphism and haplotype analyses again showed consistent , albeit weaker , results . Thus , in this biracial population sample , we find evidence that interindividual variation in the renin-angiotensin system genes contributes to hypertension risk Abstract We studied the angiotensin-converting enzyme ( ACE ) , angiotensinogen ( AGT ) , and angiotensin II type 1 receptor ( AT1R ) gene polymorphisms for association with susceptibility to primary vesicoureteral reflux ( VUR ) and disease progression in 74 Taiwanese children , including 16 with end-stage renal disease ( ESRD ) , and 117 normal controls .  Polymerase chain reaction-amplified products containing the ACE gene T-5491C , A-5466C , T-3892C , A-3692C , A-240 T , Alu I/D , the AGT gene C-532 T , G-217A , G-152A , A-20C , A-6 G , T174 M , T235 M , and the AT1R gene A-1138 T , T-810A , T-713 G , C-521 T , AG-214CC , A-153 G , A1166C polymorphisms were analyzed by restriction enzyme digestion , gel electrophoresis , or single-str and conformation polymorphism analysis . All the polymorphisms examined were in Hardy-Weinberg equilibrium . The strong non-r and om association within the ACE , AGT , and AT1R genes suggests low levels of intragenic recombination . None of these polymorphisms showed association with VUR susceptibility . However , the allele frequency distribution of the six ACE polymorphisms among primary VUR patients with or without ESRD was statistically different . The linked ACE T-A-T-A-A-I allele was observed significantly more frequently in VUR children with ESRD ( P<0.001 ) . A significant increase of left ventricular mass index was also found in the linked ACE T-A-T-A-A-I allele group compared with the non-ACE T-A-T-A-A-I allele group of patients aged 18 years with renal progression . The AGT A-6 G genotype frequencies were significantly different when the analysis was stratified by genotype of the ACE polymorphisms . The data showed that ACE gene polymorphisms were associated with progressive renal deterioration in Taiwanese children with VUR and might act synergistically with the −6 G allele of the AGT gene BACKGROUND Few studies have examined to what extent genes might modulate the changes of systolic and diastolic blood pressure ( BP ) with age although , in older population s , systolic BP and diastolic BP vary with age in opposite directions . METHODS This study involved 205 men and 99 women with either systolic-diastolic or isolated systolic hypertension . Age was > 50 years . Using polymerase chain reaction , four gene polymorphisms related to the renin-angiotensin system were independently investigated in men and women . Adjustments to cardiovascular and renal risk factors as well to the sodium/potassium extracellular space ratio were performed . RESULTS Regarding the angiotensin-converting enzyme ( ACE ) gene polymorphism , in men > 50 years of age , the slope ( mm Hg per unit of age ) of the age-diastolic BP ( and not age-systolic BP ) relationships significantly ( P = .0092 ) differed between genotypes : - 0.79 + /- 0.15 ( P < .0001 ) for the DD genotype , -0.53 + /- 0.10 for the ID genotype ( P < .0001 ) , and -0.23 + /- 0.11 for II genotypes ( P = NS ) . Such findings were not observed in the female population in which the age-diastolic BP curves were substantially flatter than in men . No comparable results were observed for gene polymorphisms related either to angiotensinogen or to angiotensin II type 1 receptor . CONCLUSIONS In men > 50 years of age , the ACE gene polymorphism modulates the physiologic age-induced reduction of diastolic BP . The D allele might contribute to enhance this reduction , a finding that needs confirmation using prospect i ve studies Sympathetic tone increases with stimulation of the renin-angiotensin system and is under the influence of salt intake . In the European Project On Genes in Hypertension ( EPOGH ) , we investigated whether polymorphisms in the genes encoding aldosterone synthase ( CYP11B2 C-344 T ) and the type-1 angiotensin II receptor ( AT1R A1166C ) affect the autonomic modulation of heart rate at varying levels of salt intake . We measured the low frequency ( LF ) and high frequency ( HF ) components of heart rate variability and their ratio ( LF : HF ) in the supine and st and ing positions in 1797 participants ( 401 families and 320 unrelated subjects ) r and omly selected from 6 European population s , whose average urinary sodium excretion ranged from 163 to 245 mmol/d . In multivariate analyses with sodium excretion analyzed as a continuous variable , we explored the phenotype-genotype associations using generalized estimating equations and quantitative transmission disequilibrium tests . Across population s , there was no heterogeneity in the phenotype-genotype relations . The genotypic effects differed according to sodium excretion . In subjects with sodium excretion < 190 mmol/d ( median ) , supine heart rate , LF , and LF : HF increased and HF decreased with the number of CYP11B2 -344 T alleles , and the orthostatic changes in LF , HF , and LF : HF were blunted in carriers of the AT1R 1166C allele . In subjects with sodium excretion  > 190 mmol/d , these associations with the CYP11B2 and AT1R polymorphisms were nonsignificant or in the opposite direction , respectively . Thus , CYP11B2 C-344 T and AT1R A1166C polymorphisms affect the autonomic modulation of heart rate , but these genetic effects depend on sodium excretion BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or  placebo .  The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes There is good evidence that physical activity reduces the risk for cardiovascular disease ( 1 - 6 ) , possibly in part by lowering blood pressure ( 7 ) . Although mild or moderate physical activity , such as brisk walking , is a recommended part of the treatment protocol for persons with hypertension ( 8 , 9 ) , it is not known whether mild physical activity , especially walking , reduces the risk for hypertension . With few exceptions , epidemiologic studies of physical activity and hypertension have been cross-sectional rather than prospect i ve . Physical activity was inversely related to blood pressure in cross-sectional and controlled studies ( 7 ) , and in two prospect i ve studies ( 10 , 11 ) , vigorous exercise was inversely related to the subsequent risk for hypertension . Physicians in Japan usually advise their patients to walk to work as often as they can , and indeed , for middle-aged working Japanese men , the journey to and from work seems to be the main source of exercise . We prospect ively examined the relation of mild physical activity , especially walking to work , and leisure-time physical activity to the risk for hypertension during 6 to 16 years of observation . Methods The Osaka Health Survey The Osaka Health Survey is an ongoing cohort study of risk factors for chronic diseases , including hypertension and diabetes . Study participants are male employees of a gas company in Osaka , Japan . Japanese law requires all employers to conduct annual health screenings for all employees . For the purpose s of the Osaka Health Survey , in addition to these annual screenings , all employees 35 years of age or older undergo more detailed biennial clinical examinations and complete question naires on health-related behaviors , including exercise . Study Sample Between 1981 and 1990 , 7979 Japanese men 35 to 63 years of age at entry who had sedentary occupations were enrolled in the study . We excluded 
    Output:
    
In conclusion , there is insufficient evidence that polymorphisms in the AGTR1 gene are risk factors for  hypertension .