human
***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: AIM Reduction of elevated blood pressure ( BP ) has been an important treatment goal in elderly hypertensive patients . However , it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients . We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy , tolerability and impact on cardiovascular/cerebrovascular ( CV ) morbidity/mortality in a large cohort of Japanese patients . METHODS This study was performed at general practitioners ' offices nationwide with a target sample size of 1500 patients . Hypertensive patients aged 60years or more who achieved successful BP control with c and esartan monotherapy , and who tolerated the treatment for at least 8weeks , were enrolled into the study and followed for 3years . RESULTS BP was maintained below the target level of 140/90mmHg over the 3-year period . The incidence of CV events during the study period was 20.4/1000person-years . Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events . However , very elderly patients ( ≥75years ) with a systolic BP ( SBP ) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120 - 139mmHg . CONCLUSION This study demonstrated that treatment with c and esartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events . CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older , which suggests that excessive BP reductions might be harmful for very elderly patients Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared . In this study , we aim ed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease . Methods We used  linked electronic health records from 1997 to 2010 in the CALIBER ( CArdiovascular research using LInked Bespoke studies and Electronic health Records ) programme to assemble a cohort of 1·25 million patients , 30 years of age or older and initially free from cardiovascular disease , a fifth of whom received blood pressure-lowering treatments . We studied the heterogeneity in the age-specific associations of clinical ly measured blood pressure with 12 acute and chronic cardiovascular diseases , and estimated the lifetime risks ( up to 95 years of age ) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30 , 60 , and 80 years . This study is registered at Clinical Trials.gov , number NCT01164371 . Findings During 5·2 years median follow-up , we recorded 83 098 initial cardiovascular disease presentations . In each age group , the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg , with no evidence of a J-shaped increased risk at lower blood pressures . The effect of high blood pressure varied by cardiovascular disease endpoint , from strongly positive to no effect . Associations with high systolic blood pressure were strongest for intracerebral haemorrhage ( hazard ratio 1·44 [ 95 % CI 1·32–1·58 ] ) , subarachnoid haemorrhage ( 1·43 [ 1·25–1·63 ] ) , and stable angina ( 1·41 [ 1·36–1·46 ] ) , and weakest for abdominal aortic aneurysm ( 1·08 [ 1·00–1·17 ] ) . Compared with diastolic blood pressure , raised systolic blood pressure had a greater effect on angina , myocardial infa rct ion , and peripheral arterial disease , whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure . Pulse pressure associations were inverse for abdominal aortic aneurysm ( HR per 10 mm Hg 0·91 [ 95 % CI 0·86–0·98 ] ) and strongest for peripheral arterial disease ( 1·23 [ 1·20–1·27 ] ) . People with  hypertension ( blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs ) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3 % ( 95 % CI 62·9–63·8 ) compared with 46·1 % ( 45·5–46·8 ) for those with normal blood pressure , and developed cardiovascular disease 5·0 years earlier ( 95 % CI 4·8–5·2 ) . Stable and unstable angina accounted for most ( 43 % ) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years , whereas heart failure and stable angina accounted for the largest proportion ( 19 % each ) of years of life lost from index age 80 years . Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range , and that diastolic and systolic associations are concordant , are not supported by the findings of this high-resolution study . Despite modern treatments , the lifetime burden of hypertension is substantial . These findings emphasise the need for new  blood pressure-lowering strategies , and will help to inform the design of r and omised trials to assess them . Funding Medical Research Council , National Institute for Health Research , and Wellcome Trust Hypertension guidelines recommend blood pressure self-measurement at home ( HBP ) , but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP . The multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure ( HOMED-BP ; 2001–2010 ) trial involved 3518 patients ( 50 % women ; mean age 59.6 years ) with an untreated systolic/diastolic HBP of 135–179/85–119 mm Hg . In a 2 × 3 design , patients were r and omized to usual control ( 125–134/80–84 mm Hg ( UC ) ) vs. tight control ( < 125/<80 mm Hg ( TC ) ) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors , angiotensin receptor blockers or calcium channel blockers . During follow-up , a computer algorithm automatically generated treatment recommendations based on HBP . At the last follow-up ( median 5.3 years ) , TC patients used more antihypertensive drugs than UC patients ( 1.82 vs. 1.74 defined daily doses , P=0.045 ) and had a greater HBP reduction ( 21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg , P=0.018/0.020 ) , but they less frequently achieved the lower HBP targets ( 37.4 vs. 63.5 % , P<0.0001 ) . The primary end point , cardiovascular death plus stroke and myocardial infa rct ion , occurred in 25 UC and 26 TC patients ( hazard ratio , 1.02 ; 95 % confidence interval , 0.59–1.77 ; P=0.94 ) . Rates were similar ( P⩾0.13 ) in the three drug groups . In all patients combined , the risk of the primary end point independently increased by 41 % ( 6–89 % ; P=0.019 ) and 47 % ( 15–87 % ; P=0.0020 ) for a 1-s.d . increase in baseline ( 12.5 mm Hg ) and follow-up ( 13.2 mm Hg ) systolic HBP . The 5-year risk was minimal ( ⩽1 % ) if on-treatment systolic HBP was 131.6 mm Hg or less . HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain . METHODS We r and omly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk , but without diabetes , to a systolic blood-pressure target of less than 120 mm Hg ( intensive treatment ) or a target of less than 140 mm Hg ( st and ard treatment ) . The primary composite outcome was myocardial infa rct ion , other acute coronary syndromes , stroke , heart failure , or death from cardiovascular causes . RESULTS At 1 year , the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the st and ard-treatment group . The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the st and ard-treatment group ( 1.65 % per year vs. 2.19 % per year ; hazard ratio with intensive treatment , 0.75 ; 95 % confidence interval [ CI ] , 0.64 to 0.89 ; P<0.001 ) . All-cause mortality was also significantly lower in the intensive-treatment group ( hazard ratio , 0.73 ; 95 % CI , 0.60 to 0.90 ; P=0.003 ) . Rates of serious adverse events of hypotension , syncope , electrolyte abnormalities , and acute kidney injury or failure , but not of injurious falls , were higher in the intensive-treatment group than in the st and ard-treatment group . CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes , targeting a systolic blood pressure of less than 120 mm Hg , as compared with less than 140 mm Hg , result ed in lower rates of fatal and nonfatal major cardiovascular events and death from any cause , although significantly higher rates of some adverse events were observed in the intensive-treatment group . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT01206062 . ) 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 Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure  , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS C 
    Output:
    
agent
There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history , except for diabetes and chronic kidney disease , for which smaller , but significant , risk reductions were detected .
β blockers were inferior to other drugs for the prevention of major cardiovascular disease events , stroke , and renal failure .
Calcium channel blockers were superior to other drugs for the prevention of stroke .
For the prevention of heart failure , calcium channel blockers were inferior and diuretics were superior to other drug classes .
INTERPRETATION Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities .
***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: AIM Reduction of elevated blood pressure ( BP ) has been an important treatment goal in elderly hypertensive patients . However , it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients . We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy , tolerability and impact on cardiovascular/cerebrovascular ( CV ) morbidity/mortality in a large cohort of Japanese patients . METHODS This study was performed at general practitioners ' offices nationwide with a target sample size of 1500 patients . Hypertensive patients aged 60years or more who achieved successful BP control with c and esartan monotherapy , and who tolerated the treatment for at least 8weeks , were enrolled into the study and followed for 3years . RESULTS BP was maintained below the target level of 140/90mmHg over the 3-year period . The incidence of CV events during the study period was 20.4/1000person-years . Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events . However , very elderly patients ( ≥75years ) with a systolic BP ( SBP ) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120 - 139mmHg . CONCLUSION This study demonstrated that treatment with c and esartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events . CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older , which suggests that excessive BP reductions might be harmful for very elderly patients Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared . In this study , we aim ed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease . Methods We used  linked electronic health records from 1997 to 2010 in the CALIBER ( CArdiovascular research using LInked Bespoke studies and Electronic health Records ) programme to assemble a cohort of 1·25 million patients , 30 years of age or older and initially free from cardiovascular disease , a fifth of whom received blood pressure-lowering treatments . We studied the heterogeneity in the age-specific associations of clinical ly measured blood pressure with 12 acute and chronic cardiovascular diseases , and estimated the lifetime risks ( up to 95 years of age ) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30 , 60 , and 80 years . This study is registered at Clinical Trials.gov , number NCT01164371 . Findings During 5·2 years median follow-up , we recorded 83 098 initial cardiovascular disease presentations . In each age group , the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg , with no evidence of a J-shaped increased risk at lower blood pressures . The effect of high blood pressure varied by cardiovascular disease endpoint , from strongly positive to no effect . Associations with high systolic blood pressure were strongest for intracerebral haemorrhage ( hazard ratio 1·44 [ 95 % CI 1·32–1·58 ] ) , subarachnoid haemorrhage ( 1·43 [ 1·25–1·63 ] ) , and stable angina ( 1·41 [ 1·36–1·46 ] ) , and weakest for abdominal aortic aneurysm ( 1·08 [ 1·00–1·17 ] ) . Compared with diastolic blood pressure , raised systolic blood pressure had a greater effect on angina , myocardial infa rct ion , and peripheral arterial disease , whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure . Pulse pressure associations were inverse for abdominal aortic aneurysm ( HR per 10 mm Hg 0·91 [ 95 % CI 0·86–0·98 ] ) and strongest for peripheral arterial disease ( 1·23 [ 1·20–1·27 ] ) . People with  hypertension ( blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs ) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3 % ( 95 % CI 62·9–63·8 ) compared with 46·1 % ( 45·5–46·8 ) for those with normal blood pressure , and developed cardiovascular disease 5·0 years earlier ( 95 % CI 4·8–5·2 ) . Stable and unstable angina accounted for most ( 43 % ) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years , whereas heart failure and stable angina accounted for the largest proportion ( 19 % each ) of years of life lost from index age 80 years . Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range , and that diastolic and systolic associations are concordant , are not supported by the findings of this high-resolution study . Despite modern treatments , the lifetime burden of hypertension is substantial . These findings emphasise the need for new  blood pressure-lowering strategies , and will help to inform the design of r and omised trials to assess them . Funding Medical Research Council , National Institute for Health Research , and Wellcome Trust Hypertension guidelines recommend blood pressure self-measurement at home ( HBP ) , but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP . The multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure ( HOMED-BP ; 2001–2010 ) trial involved 3518 patients ( 50 % women ; mean age 59.6 years ) with an untreated systolic/diastolic HBP of 135–179/85–119 mm Hg . In a 2 × 3 design , patients were r and omized to usual control ( 125–134/80–84 mm Hg ( UC ) ) vs. tight control ( < 125/<80 mm Hg ( TC ) ) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors , angiotensin receptor blockers or calcium channel blockers . During follow-up , a computer algorithm automatically generated treatment recommendations based on HBP . At the last follow-up ( median 5.3 years ) , TC patients used more antihypertensive drugs than UC patients ( 1.82 vs. 1.74 defined daily doses , P=0.045 ) and had a greater HBP reduction ( 21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg , P=0.018/0.020 ) , but they less frequently achieved the lower HBP targets ( 37.4 vs. 63.5 % , P<0.0001 ) . The primary end point , cardiovascular death plus stroke and myocardial infa rct ion , occurred in 25 UC and 26 TC patients ( hazard ratio , 1.02 ; 95 % confidence interval , 0.59–1.77 ; P=0.94 ) . Rates were similar ( P⩾0.13 ) in the three drug groups . In all patients combined , the risk of the primary end point independently increased by 41 % ( 6–89 % ; P=0.019 ) and 47 % ( 15–87 % ; P=0.0020 ) for a 1-s.d . increase in baseline ( 12.5 mm Hg ) and follow-up ( 13.2 mm Hg ) systolic HBP . The 5-year risk was minimal ( ⩽1 % ) if on-treatment systolic HBP was 131.6 mm Hg or less . HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain . METHODS We r and omly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk , but without diabetes , to a systolic blood-pressure target of less than 120 mm Hg ( intensive treatment ) or a target of less than 140 mm Hg ( st and ard treatment ) . The primary composite outcome was myocardial infa rct ion , other acute coronary syndromes , stroke , heart failure , or death from cardiovascular causes . RESULTS At 1 year , the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the st and ard-treatment group . The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the st and ard-treatment group ( 1.65 % per year vs. 2.19 % per year ; hazard ratio with intensive treatment , 0.75 ; 95 % confidence interval [ CI ] , 0.64 to 0.89 ; P<0.001 ) . All-cause mortality was also significantly lower in the intensive-treatment group ( hazard ratio , 0.73 ; 95 % CI , 0.60 to 0.90 ; P=0.003 ) . Rates of serious adverse events of hypotension , syncope , electrolyte abnormalities , and acute kidney injury or failure , but not of injurious falls , were higher in the intensive-treatment group than in the st and ard-treatment group . CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes , targeting a systolic blood pressure of less than 120 mm Hg , as compared with less than 140 mm Hg , result ed in lower rates of fatal and nonfatal major cardiovascular events and death from any cause , although significantly higher rates of some adverse events were observed in the intensive-treatment group . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT01206062 . ) 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 Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure  , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS C 
    Output:
    