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: Background In the Systolic Hypertension in Europe trial ( NCT02088450 ) , we investigated whether systolic blood pressure variability determines prognosis over and beyond level . Methods Using a computerised r and om function and a double-blind design , we r and omly allocated 4695 patients ( ≥60 years ) with isolated systolic hypertension ( 160–219/<95 mm Hg ) to active treatment or matching placebo . Active treatment consisted of nitrendipine ( 10–40 mg/day ) with possible addition of enalapril ( 5–20 mg/day ) and /or hydrochlorothiazide ( 12.5–25.0 mg/day ) . We assessed whether on-treatment systolic blood pressure level ( SBP ) , visit-to-visit variability independent of the mean ( VIM ) or within-visit variability ( WVV ) predicted total ( n = 286 ) or cardiovascular ( n = 150 ) mortality or cardiovascular ( n = 347 ) , cerebrovascular ( n = 133 ) or cardiac ( n = 217 ) endpoints . Findings At 2 years , mean between-group differences were 10.5 mm Hg ( p<0.0001 ) for SBP , 0.29 units ( p = 0.20 ) for VIM , and 0.07 mm Hg ( p = 0.47 ) for WVV . Active treatment reduced ( p≤0.048 ) cardiovascular ( −28 % ) , cerebrovascular ( −40 % ) and cardiac ( −24 % ) endpoints . In analyses dichotomised by the median , patients with low vs. high VIM had similar event rates ( p≥0.14 ) . Low vs. high WVV was not associated with event rates ( p≥0.095 ) , except for total and cardiovascular mortality on active treatment , which were higher with low WVV ( p≤0.0003 ) . In multivariable-adjusted Cox models , SBP predicted all endpoints ( p≤0.0043 ) , whereas VIM did not predict any ( p≥0.058 ) . Except for an inverse association with total mortality ( p = 0.042 ) , WVV was not predictive ( p≥0.15 ) . Sensitivity analyses , from which we excluded blood pressure readings within 6 months after r and omisation , 6 months prior to an event or both were confirmatory . Conclusions The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP . Higher blood pressure level , but not higher variability , predicted risk . Trial Registration Clinical Trials.gov No adverse effect upon cognitive function has been detected during the first 9 months of treatment by a thiazide diuretic ( Moduretic ; Merck Sharp & Dohme , Hoddesdon , UK ) or a beta-blocking agent ( atenolol ) of moderately elevated blood pressure in a cohort of 2630 men and women aged between 65 and 74 years . Furthermore , no association was discovered between levels of systolic or diastolic blood pressure at outset and responses to st and ard tests of cognitive function . This study was carried out in general practice s as part of the current Medical Research Council Treatment Trial of Mild Hypertension in the Elderly Nine-hundred- and -twenty-two hypertensive patients were included in a sub study to the Hypertension Optimal Treatment study , which aim ed to investigate the impact on quality of life of lowering the pressure and of intensified therapy .  Seven-hundred- and -eighty-one patients completed both baseline and follow-up question naires ( intention-to-treat population ) , while 610 patients were included in a per protocol analysis . Patients were r and omized to three diastolic BP levels ( DBPs ) , i.e. < or = 90 mmHg , < or = 85 mmHg and < or = 80 mmHg . Two self-administered vali date d question naires , the  Psychological General Well-Being index and the Subjective Symptoms Assessment Profile ( SSA-P )  were completed at baseline and after 6 months . The lower the DBP achieved , the greater the improvement in well-being ( p < 0.05 ) . The increase in well-being from baseline to 6 months was significant in target groups < or = 80 mmHg ( p < 0.01 ) and < or = 85 mmHg ( p < 0.05 ) . The SSA-P domains , cardiac symptoms and dizziness improved in all groups but the sex life score deteriorated in the < or = 80 and < or = 85 mmHg groups in male patients . In all target groups , headaches were reduced ( p < 0.001 ) , while swollen ankles ( p < 0.001 ) and dry cough in the < or = 80 mmHg group ( p < 0.001 ) increased . Although more intensive antihypertensive therapy is associated with a slight increase in subjective symptoms , it is nonetheless still associated with improvements in patients ' well-being OBJECTIVE To assess the effectiveness of nifedipine treatment in elderly hypertensives . METHODS A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60 - 79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months . Clinical events and risk modification were analysed in collaboration with the University of Montreal . Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in . RESULTS Cox 's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events : ' original treatment assignment ' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group . Similar significance s were achieved with ' actual treatment ' or ' changes excluded ' ( excluding reallocated subjects ) analyses . A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 ( 95 % confidence interval 0.27 - 0.61 ) . CONCLUSION Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets Objective To compare quality of life in elderly patients with isolated systolic hypertension allocated r and omly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial . Design Double-blind r and omized controlled trial . Methods Patients aged 60 years were allocated r and omly to groups to receive first-line treatment with nitrendipine ( with second- and third-line enalapril and hydrochlorothiazide ) or placebo . Trained interviewers administered trail-making tests ( Trail A and B ) , Brief Assessment Index ( a measure of depressed mood ) and four subscales from the Sickness Impact Profile ( Ambulation , Social Interaction , Sleep and Rest , and Home work ) . Results Six hundred and ten patients completed a baseline and at least one follow-up question naire . Trail-making scores were slower in actively treated patients , especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [ 95 % confidence interval ( CI ) 0.07 to 0.43 ] for Trail-making A and 0.13 ( 95 % CI −0.05 to 0.31 ) for Trail-making B. Across the 4 years of follow-up , patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients ( odds ratio 1.32 , 95 % CI 1.02 to 1.69 ) , equivalent to a 7 % difference . There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression .  Conclusions Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo .  The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at 
    Output:
    
agent
Benefits of Treating Higher Versus Lower BP Targets in Older Adults Across all trials , treating high BP in older adults was beneficial .
This is probably related to the higher frequency of cardiovascular events seen in these patients .
Treatment Effects According to Diastolic BP Evidence was insufficient to determine the benefit of treating diastolic hypertension in the absence of systolic hypertension .
A subgroup analysis of SPRINT showed a nonstatistically significant increase in the rate of serious adverse events , hypotension , syncope , electrolyte abnormalities , or acute
***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 In the Systolic Hypertension in Europe trial ( NCT02088450 ) , we investigated whether systolic blood pressure variability determines prognosis over and beyond level . Methods Using a computerised r and om function and a double-blind design , we r and omly allocated 4695 patients ( ≥60 years ) with isolated systolic hypertension ( 160–219/<95 mm Hg ) to active treatment or matching placebo . Active treatment consisted of nitrendipine ( 10–40 mg/day ) with possible addition of enalapril ( 5–20 mg/day ) and /or hydrochlorothiazide ( 12.5–25.0 mg/day ) . We assessed whether on-treatment systolic blood pressure level ( SBP ) , visit-to-visit variability independent of the mean ( VIM ) or within-visit variability ( WVV ) predicted total ( n = 286 ) or cardiovascular ( n = 150 ) mortality or cardiovascular ( n = 347 ) , cerebrovascular ( n = 133 ) or cardiac ( n = 217 ) endpoints . Findings At 2 years , mean between-group differences were 10.5 mm Hg ( p<0.0001 ) for SBP , 0.29 units ( p = 0.20 ) for VIM , and 0.07 mm Hg ( p = 0.47 ) for WVV . Active treatment reduced ( p≤0.048 ) cardiovascular ( −28 % ) , cerebrovascular ( −40 % ) and cardiac ( −24 % ) endpoints . In analyses dichotomised by the median , patients with low vs. high VIM had similar event rates ( p≥0.14 ) . Low vs. high WVV was not associated with event rates ( p≥0.095 ) , except for total and cardiovascular mortality on active treatment , which were higher with low WVV ( p≤0.0003 ) . In multivariable-adjusted Cox models , SBP predicted all endpoints ( p≤0.0043 ) , whereas VIM did not predict any ( p≥0.058 ) . Except for an inverse association with total mortality ( p = 0.042 ) , WVV was not predictive ( p≥0.15 ) . Sensitivity analyses , from which we excluded blood pressure readings within 6 months after r and omisation , 6 months prior to an event or both were confirmatory . Conclusions The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP . Higher blood pressure level , but not higher variability , predicted risk . Trial Registration Clinical Trials.gov No adverse effect upon cognitive function has been detected during the first 9 months of treatment by a thiazide diuretic ( Moduretic ; Merck Sharp & Dohme , Hoddesdon , UK ) or a beta-blocking agent ( atenolol ) of moderately elevated blood pressure in a cohort of 2630 men and women aged between 65 and 74 years . Furthermore , no association was discovered between levels of systolic or diastolic blood pressure at outset and responses to st and ard tests of cognitive function . This study was carried out in general practice s as part of the current Medical Research Council Treatment Trial of Mild Hypertension in the Elderly Nine-hundred- and -twenty-two hypertensive patients were included in a sub study to the Hypertension Optimal Treatment study , which aim ed to investigate the impact on quality of life of lowering the pressure and of intensified therapy .  Seven-hundred- and -eighty-one patients completed both baseline and follow-up question naires ( intention-to-treat population ) , while 610 patients were included in a per protocol analysis . Patients were r and omized to three diastolic BP levels ( DBPs ) , i.e. < or = 90 mmHg , < or = 85 mmHg and < or = 80 mmHg . Two self-administered vali date d question naires , the  Psychological General Well-Being index and the Subjective Symptoms Assessment Profile ( SSA-P )  were completed at baseline and after 6 months . The lower the DBP achieved , the greater the improvement in well-being ( p < 0.05 ) . The increase in well-being from baseline to 6 months was significant in target groups < or = 80 mmHg ( p < 0.01 ) and < or = 85 mmHg ( p < 0.05 ) . The SSA-P domains , cardiac symptoms and dizziness improved in all groups but the sex life score deteriorated in the < or = 80 and < or = 85 mmHg groups in male patients . In all target groups , headaches were reduced ( p < 0.001 ) , while swollen ankles ( p < 0.001 ) and dry cough in the < or = 80 mmHg group ( p < 0.001 ) increased . Although more intensive antihypertensive therapy is associated with a slight increase in subjective symptoms , it is nonetheless still associated with improvements in patients ' well-being OBJECTIVE To assess the effectiveness of nifedipine treatment in elderly hypertensives . METHODS A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60 - 79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months . Clinical events and risk modification were analysed in collaboration with the University of Montreal . Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in . RESULTS Cox 's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events : ' original treatment assignment ' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group . Similar significance s were achieved with ' actual treatment ' or ' changes excluded ' ( excluding reallocated subjects ) analyses . A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 ( 95 % confidence interval 0.27 - 0.61 ) . CONCLUSION Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets Objective To compare quality of life in elderly patients with isolated systolic hypertension allocated r and omly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial . Design Double-blind r and omized controlled trial . Methods Patients aged 60 years were allocated r and omly to groups to receive first-line treatment with nitrendipine ( with second- and third-line enalapril and hydrochlorothiazide ) or placebo . Trained interviewers administered trail-making tests ( Trail A and B ) , Brief Assessment Index ( a measure of depressed mood ) and four subscales from the Sickness Impact Profile ( Ambulation , Social Interaction , Sleep and Rest , and Home work ) . Results Six hundred and ten patients completed a baseline and at least one follow-up question naire . Trail-making scores were slower in actively treated patients , especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [ 95 % confidence interval ( CI ) 0.07 to 0.43 ] for Trail-making A and 0.13 ( 95 % CI −0.05 to 0.31 ) for Trail-making B. Across the 4 years of follow-up , patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients ( odds ratio 1.32 , 95 % CI 1.02 to 1.69 ) , equivalent to a 7 % difference . There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression .  Conclusions Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo .  The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at 
    Output:
    