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: OBJECTIVE Blood pressure control can reduce the risk of coronary heart disease ( CHD ) among diabetic patients ; however , it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level . RESEARCH DESIGN AND METHODS We performed a prospect i ve cohort  study ( 2000–2009 ) on diabetic patients including 17,536 African Americans and 12,618 whites . Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk . RESULTS During a mean follow-up of 6.0 years , 7,260 CHD incident cases were identified . The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline ( < 110/65 , 110–119/65–69 , 120–129/70–80 , and 130–139/80–90 mmHg [ reference group ] ; 140–159/90–100 ; and ≥160/100 mmHg ) were 1.73 , 1.16 , 1.04 , 1.00 , 1.06 , and 1.11 ( P trend < 0.001 ) , respectively , for African American diabetic patients , and 1.60 , 1.27 , 1.08 , 1.00 , 0.95 , and 0.99 ( P trend<0.001 ) for white diabetic patients , respectively . A U-shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients ( all Ptrend < 0.001 ) . The U-shaped association was present in the younger age-group ( 30–49 years ) , and this U-shaped association changed to an inverse association in the older age-group ( ≥60 years ) . CONCLUSIONS Our study suggests that there is a U-shaped or inverse association between blood pressure and the risk of CHD , and aggressive blood pressure control ( blood pressure < 120/70 mmHg ) is associated with an increased risk of CHD among both African American and white patients with diabetes BACKGROUND AND OBJECTIVES The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown ; neither is it clear whether in patients with a previous cardiovascular event , the optimal values are lower than in the low-to-moderate risk hypertensive patients , or a more cautious blood pressure ( BP ) reduction should be obtained . Because of the uncertainty whether ' the lower the better ' or the ' J-curve ' hypothesis is correct , the European Society of Hypertension and the Chinese Hypertension League have promoted a r and omized trial comparing antihypertensive treatment strategies aim ing at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack . As the optimal level of low-density lipoprotein cholesterol ( LDL-C ) level is also unknown in these patients , LDL-C-lowering has been included in the design . PROTOCOL DESIGN The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospect i ve multinational , r and omized trial with a 3 × 2 factorial design comparing : three different SBP targets ( 1 , < 145 - 135 ; 2 , < 135 - 125 ; 3 , < 125 mmHg ) ; two different LDL-C targets ( target A , 2.8 - 1.8 ; target B , < 1.8 mmol/l ) . The trial is to be conducted on 7500 patients aged at least 65 years ( 2500 in Europe , 5000 in China ) with hypertension and a stroke or transient ischaemic attack 1 - 6 months before r and omization .  Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators , in order to maintain patients within the r and omized SBP and LDL-C windows . All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly . OUTCOMES Primary outcome is time to stroke ( fatal and non-fatal ) . Important secondary outcomes are : time to first major cardiovascular event ; cognitive decline ( Montreal Cognitive Assessment ) and dementia . All major outcomes will be adjudicated by committees blind to r and omized allocation . A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety . SAMPLE SIZE CALCULATION It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up , and this should provide at least 80 % power to detect a 25 % stroke difference between SBP targets and a 20 % difference between LDL-C targets CONTEXT Medical evidence may be biased over time if completion and publication of r and omized efficacy trials are delayed when results are not statistically significant . OBJECTIVE To evaluate whether the time to completion and the time to publication of r and omized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials . DESIGN Prospect i ve cohort of r and omized efficacy trials conducted by 2 trialist groups from 1986 to 1996 . SETTING Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health . PATIENTS A total of 109 efficacy trials ( total enrollment , 43708 patients ) . MAIN OUTCOME MEASURES Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer- review ed publication assessed with survival analysis . RESULTS The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm ( 6.5 vs 4.3 years , respectively ; P<.001 ; hazard ratio for time to publication for positive vs negative trials , 3.7 ; 95 % confidence interval [ CI ] , 1.8 - 7.7 ) . This difference was mostly attributable to differences in the time from completion to publication ( median , 3.0 vs 1.7 years for negative vs positive trials ; P<.001 ) . On average , trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results ( median , 2.3 vs 2.5 years ; P=.045 ) , but long-protracted trials often had low event rates and failed to reach statistical significance , while trials that were terminated early had significant results . Positive trials were su bmi tted for publication significantly more rapidly after completion than were negative trials ( median , 1.0 vs 1.6 years ; P=.001 ) and were published more rapidly after su bmi ssion ( median , 0.8 vs 1.1 years ; P=.04 ) . CONCLUSION Among r and omized efficacy trials , there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality CONTEXT The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease ( CAD ) and normal blood pressure remains uncertain . OBJECTIVE To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter , 24-month trial ( enrollment April 1999-April 2002 ) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD ( > 20 % stenosis by coronary angiography ) and diastolic blood pressure < 100 mm Hg . A sub study of 274 patients measured atherosclerosis progression by intravascular ultrasound ( IVUS ) . INTERVENTIONS Patients were r and omized to receive amlodipine , 10 mg ; enalapril , 20 mg ; or placebo . IVUS was performed at baseline and study completion . MAIN OUTCOME MEASURES The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo . Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo . Events included cardiovascular death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , coronary revascularization , hospitalization for angina pectoris , hospitalization for congestive heart failure , fatal or nonfatal stroke or transient ischemic attack , and new diagnosis of peripheral vascular disease . The IVUS end point was change in percent atheroma volume . RESULTS Baseline blood pressure averaged 129/78 mm Hg for all patients ; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups , respectively ( P<.001 for both vs placebo ) 
    Output:
    
agent
CONCLUSIONS Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg .
If systolic blood pressure is less than 140 mm Hg , however , further treatment is associated with an increased risk of cardiovascular death , with no observed benefit
***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: OBJECTIVE Blood pressure control can reduce the risk of coronary heart disease ( CHD ) among diabetic patients ; however , it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level . RESEARCH DESIGN AND METHODS We performed a prospect i ve cohort  study ( 2000–2009 ) on diabetic patients including 17,536 African Americans and 12,618 whites . Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk . RESULTS During a mean follow-up of 6.0 years , 7,260 CHD incident cases were identified . The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline ( < 110/65 , 110–119/65–69 , 120–129/70–80 , and 130–139/80–90 mmHg [ reference group ] ; 140–159/90–100 ; and ≥160/100 mmHg ) were 1.73 , 1.16 , 1.04 , 1.00 , 1.06 , and 1.11 ( P trend < 0.001 ) , respectively , for African American diabetic patients , and 1.60 , 1.27 , 1.08 , 1.00 , 0.95 , and 0.99 ( P trend<0.001 ) for white diabetic patients , respectively . A U-shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients ( all Ptrend < 0.001 ) . The U-shaped association was present in the younger age-group ( 30–49 years ) , and this U-shaped association changed to an inverse association in the older age-group ( ≥60 years ) . CONCLUSIONS Our study suggests that there is a U-shaped or inverse association between blood pressure and the risk of CHD , and aggressive blood pressure control ( blood pressure < 120/70 mmHg ) is associated with an increased risk of CHD among both African American and white patients with diabetes BACKGROUND AND OBJECTIVES The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown ; neither is it clear whether in patients with a previous cardiovascular event , the optimal values are lower than in the low-to-moderate risk hypertensive patients , or a more cautious blood pressure ( BP ) reduction should be obtained . Because of the uncertainty whether ' the lower the better ' or the ' J-curve ' hypothesis is correct , the European Society of Hypertension and the Chinese Hypertension League have promoted a r and omized trial comparing antihypertensive treatment strategies aim ing at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack . As the optimal level of low-density lipoprotein cholesterol ( LDL-C ) level is also unknown in these patients , LDL-C-lowering has been included in the design . PROTOCOL DESIGN The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospect i ve multinational , r and omized trial with a 3 × 2 factorial design comparing : three different SBP targets ( 1 , < 145 - 135 ; 2 , < 135 - 125 ; 3 , < 125 mmHg ) ; two different LDL-C targets ( target A , 2.8 - 1.8 ; target B , < 1.8 mmol/l ) . The trial is to be conducted on 7500 patients aged at least 65 years ( 2500 in Europe , 5000 in China ) with hypertension and a stroke or transient ischaemic attack 1 - 6 months before r and omization .  Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators , in order to maintain patients within the r and omized SBP and LDL-C windows . All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly . OUTCOMES Primary outcome is time to stroke ( fatal and non-fatal ) . Important secondary outcomes are : time to first major cardiovascular event ; cognitive decline ( Montreal Cognitive Assessment ) and dementia . All major outcomes will be adjudicated by committees blind to r and omized allocation . A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety . SAMPLE SIZE CALCULATION It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up , and this should provide at least 80 % power to detect a 25 % stroke difference between SBP targets and a 20 % difference between LDL-C targets CONTEXT Medical evidence may be biased over time if completion and publication of r and omized efficacy trials are delayed when results are not statistically significant . OBJECTIVE To evaluate whether the time to completion and the time to publication of r and omized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials . DESIGN Prospect i ve cohort of r and omized efficacy trials conducted by 2 trialist groups from 1986 to 1996 . SETTING Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health . PATIENTS A total of 109 efficacy trials ( total enrollment , 43708 patients ) . MAIN OUTCOME MEASURES Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer- review ed publication assessed with survival analysis . RESULTS The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm ( 6.5 vs 4.3 years , respectively ; P<.001 ; hazard ratio for time to publication for positive vs negative trials , 3.7 ; 95 % confidence interval [ CI ] , 1.8 - 7.7 ) . This difference was mostly attributable to differences in the time from completion to publication ( median , 3.0 vs 1.7 years for negative vs positive trials ; P<.001 ) . On average , trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results ( median , 2.3 vs 2.5 years ; P=.045 ) , but long-protracted trials often had low event rates and failed to reach statistical significance , while trials that were terminated early had significant results . Positive trials were su bmi tted for publication significantly more rapidly after completion than were negative trials ( median , 1.0 vs 1.6 years ; P=.001 ) and were published more rapidly after su bmi ssion ( median , 0.8 vs 1.1 years ; P=.04 ) . CONCLUSION Among r and omized efficacy trials , there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality CONTEXT The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease ( CAD ) and normal blood pressure remains uncertain . OBJECTIVE To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter , 24-month trial ( enrollment April 1999-April 2002 ) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD ( > 20 % stenosis by coronary angiography ) and diastolic blood pressure < 100 mm Hg . A sub study of 274 patients measured atherosclerosis progression by intravascular ultrasound ( IVUS ) . INTERVENTIONS Patients were r and omized to receive amlodipine , 10 mg ; enalapril , 20 mg ; or placebo . IVUS was performed at baseline and study completion . MAIN OUTCOME MEASURES The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo . Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo . Events included cardiovascular death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , coronary revascularization , hospitalization for angina pectoris , hospitalization for congestive heart failure , fatal or nonfatal stroke or transient ischemic attack , and new diagnosis of peripheral vascular disease . The IVUS end point was change in percent atheroma volume . RESULTS Baseline blood pressure averaged 129/78 mm Hg for all patients ; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups , respectively ( P<.001 for both vs placebo ) 
    Output:
    