***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 We have investigated the possible effects of contrasting ACE ( I/D ) genotypes on the responses to the ACE inhibitor enalaprilat in normotensive men . METHODS AND RESULTS Subjects with DD ( n=12 ) and II ( n=11 ) ACE genotypes received an intravenous infusion of enalaprilat or placebo .  Pressor responses to stepwise , incremental doses of angiotensin I were measured at 1 and 10 hours after dosing . The dose required to raise mean blood pressure by 20 mm Hg ( PD20 ) was calculated individually , and the ratio of PD20 during enalaprilat to that during placebo ( dose ratio , DR ) was used for assessment of the extent of ACE inhibition . The pressor response was significantly attenuated at 1 hour after enalaprilat in both groups , but significant attenuation was evident at 10 hours after dose only in the II subjects . The DRs at both 1 hour ( median , 5.43 versus 2.82 , P=0.0035 ) and 10 hours ( 2.06 versus 0.84 , P=0.0008 ) after enalaprilat were significantly higher in II subjects than in DD subjects . CONCLUSIONS The effect of enalaprilat was significantly greater and lasted longer in normotensive men homozygous for the II ACE genotype . By multivariate analysis , ACE ( I/D ) genotype and plasma angiotensin II levels were predictive of > 50 % of the variation in response to ACE inhibition 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 BACKGROUND Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk . We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension . METHODS Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower , or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg , were r and omly assigned to receive two years of c and esartan ( Atac and , AstraZeneca ) or placebo , followed by two years of placebo for all . When a participant reached the study end point of stage 1 hypertension , treatment with antihypertensive agents was initiated . Both the c and esartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial . RESULTS A total of 409 participants were r and omly assigned to c and esartan , and 400 to placebo . Data on 772 participants ( 391 in the c and esartan group and 381 in the placebo group ; mean age , 48.5 years ; 59.6 percent men ) were available for analysis . During the first two years , hypertension developed in 154 participants in the placebo group and 53 of those in the c and esartan group ( relative risk reduction , 66.3 percent ; P<0.001 ) . After four years , hypertension had developed in 240 participants in the placebo group and 208 of those in the c and esartan group ( relative risk reduction , 15.6 percent ; P<0.007 ) . Serious adverse events occurred in 3.5 percent of the participants assigned to c and esartan and 5.9 percent of those receiving placebo . CONCLUSIONS Over a period of four years , stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension ( the placebo group ) . Treatment of prehypertension with c and esartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period . Thus , treatment of prehypertension appears to be feasible . ( Clinical Trials.gov number , NCT00227318 . ) The aim of this study was to investigate the relationship between polymorphism of the anglotensin-converting enzyme ( ACE ) gene and the blood pressure response to ACE inhibition in a hypertensive cohort .  Imidapril ( 5 - 10 mg/day ) or benazepril ( 10 - 20 mg/day ) was administered for 6 weeks to 517 essential hypertensives . ACE gene polymorphism was examined by the polymerase chain reaction ( PCR ) method and the patients were classified as having the 190-bp deletion homozygous ( DD ) genotype , the 490-bp insertion homozygous ( II ) genotype , or the 490-bp insertion , 190-bp deletion heterozygous ( ID ) genotype . The achieved change in systolic and diastolic blood pressure ( SBP and DBP ) was analyzed for association with genotypes at the ACE gene locus . The DD genotype was observed in 132 patients ( 25.5 % ) , the ID genotype in 255 patients ( 49.3 % ) , and the II genotype in 130 patients ( 25.2 % ) . The SBP reductions in the patients with the DD genotype , II genotype , and ID genotype were -14.5 + /- 12.7 mmHg , -14.3 + /- 13.1 mmHg and -14.0 + /- 12.2 mmHg , respectively ( p = 0.94 ) . The DBP reductions in the patients with the DD genotype , II genotype , and ID genotype were -8.7 + /- 7.4 mmHg , -8.7 + /- 7.7 mmHg and -8.5 + /- 6.7 mmHg , respectively ( p = 0.96 ) . There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition . These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure Background —Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system , but no clinical trails have tested whether the ACE insertion/deletion ( I/D ) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes . Methods and Results —We used a double-blind , active-controlled r and omized trial of antihypertensive treatment that included hypertensives ≥55 years of age with ≥1 risk factor for cardiovascular disease . ACE I/D genotypes were determined in 37 939 participants r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin treatments and followed up for 4 to 8 years . Primary outcomes included fatal coronary heart disease ( CHD ) and /or nonfatal myocardial infa rct ion . Secondary outcomes included stroke , all-cause mortality , combined CHD , and combined cardiovascular disease .  Fatal and nonfatal CHD occurred in 3096 individuals during follow-up . The hazard rates for fatal and nonfatal CHD and the secondary outcomes were similar across antihypertensive treatments . ACE I/D genotype group was not associated with fatal and nonfatal CHD ( relative risk of DD versus ID and II , 0.99 ; 95 % CI , 0.91 to 1.07 ) or any secondary outcome . The 6-year hazard rate for fatal and nonfatal CHD in the DD genotype group was not statistically different from the ID and II genotype group by type of treatment . No secondary outcome measure was statistically different across antihypertensive treatment and ACE I/D genotype strata . Conclusions —ACE I/D genotype group was not a predictor of CHD , nor did it modify the response to antihypertensive treatment . We conclude that the ACE I/D polymorphism is not a useful marker to predict antihypertensive treatment response BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity .  Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by 
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From the results , we were able to draw conclusions with nearly consistent findings that the conventional genetic variants of the system ( i.e. , the ACE I/D , AGT M235 T , AT1 A1166C , and AT2 variant ) are not associated with antihypertensive effects by RAS blockade , at least by one individual SNP .