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 — Early after  coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications , we compared glomerular filtration rate ( GFR ; primary outcome ) , cardiovascular events , retinopathy , and neuropathy in 380 hypertensive type 2 diabetics with albuminuria < 200 mg/min included in a multicenter , double-blind , placebo-controlled trial ( DEM AND [ Delapril and Manidipine for Nephroprotection in Diabetes ] ) and r and omized to 3-year treatment with manidipine/delapril combination ( 10/30 mg/d ; n=126 ) , delapril ( 30 mg/d ; n=127 ) , or placebo ( n=127 ) . GFR was central ly measured by iohexol plasma clearance . Median monthly GFR decline ( interquartile range [ IQR ] ) was 0.32 mL/min per 1.73 m2 ( IQR : 0.16–0.50 mL/min per 1.73 m2 ) on combined therapy , 0.36 mL/min per 1.73 m2 ( IQR : 0.18–0.53 mL/min per 1.73 m2 ) on delapril , and 0.30 mL/min per 1.73 m2 ( IQR : 0.12–0.50 mL/min per 1.73 m2 ) on placebo ( P=0.87 and P=0.53 versus combined therapy or delapril , respectively ) . Similar findings were observed when baseline GFR values were not considered for slope analyses . Albuminuria was stable in the 3 treatment groups . The hazard ratio ( 95 % CI ) for major cardiovascular events between combined therapy and placebo was 0.17 ( 0.04–0.78 ; P=0.023 ) . Among 192 subjects without retinopathy at inclusion , the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 ( 0.07–0.99 ; P=0.048 ) . Among 200 subjects with central ized neurological evaluation , the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 ( 0.24–0.87 ; P=0.017 ) and 0.52 ( 0.27–0.99 ; P=0.048 ) , respectively . Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo ( P=0.03 ) but did not change on combined or delapril therapy . Treatment was well tolerated . In hypertensive type 2 diabetic patients , combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease , retinopathy , and neuropathy and stabilized insulin sensitivity PURPOSE To evaluate the effect of long-term treatment with metoprolol after coronary bypass grafting on death and cardiac events . METHODS Patients in western Sweden on whom coronary artery bypass grafting was performed between June 1988 and June 1991 were evaluated for inclusion during the first 3 weeks after surgery . Major exclusion criteria were age > 75 years , concomitant valve surgery , traditional contraindications to beta-blockers and unwillingness to participate . Patients were r and omized in a double-blind fashion to 100 mg of metoprolol/placebo daily for 2 weeks and thereafter 200 mg daily for 2 years . RESULTS Of 2365 patients who were operated on , 967 were r and omized to either metoprolol ( n = 480 ) or placebo ( n = 487 ) . Primary end points ( death , non-fatal myocardial infa rct ion , unstable angina pectoris , need for coronary artery bypass grafting or percutaneous transluminal angioplasty ) , were reached by 42 patients in the metoprolol group ( 8.8 % ) , as compared with 39 in the placebo group ( 8.0 % ) ( P = 0.73 ) . Of all the patients r and omized to metoprolol , 34 % withdrew from blind treatment prematurely compared with 44 % for placebo ( P < 0.01 ) . CONCLUSION Prophylactic treatment with metoprolol over a 2-year period after coronary artery bypass grafting did not reduce death or the development of cardiac events . However , the 95 % confidence limits ranged from the possibility of a 30 % reduction in events to a 68 % increase in events if patients were treated with metoprolol as compared with placebo Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril  reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events  . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths 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 % 
    Output:
    
agent
In primary prevention , the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP ( SBP ) .
Conclusions and Relevance Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher .
At lower BP levels , treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD
***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 — Early after  coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications , we compared glomerular filtration rate ( GFR ; primary outcome ) , cardiovascular events , retinopathy , and neuropathy in 380 hypertensive type 2 diabetics with albuminuria < 200 mg/min included in a multicenter , double-blind , placebo-controlled trial ( DEM AND [ Delapril and Manidipine for Nephroprotection in Diabetes ] ) and r and omized to 3-year treatment with manidipine/delapril combination ( 10/30 mg/d ; n=126 ) , delapril ( 30 mg/d ; n=127 ) , or placebo ( n=127 ) . GFR was central ly measured by iohexol plasma clearance . Median monthly GFR decline ( interquartile range [ IQR ] ) was 0.32 mL/min per 1.73 m2 ( IQR : 0.16–0.50 mL/min per 1.73 m2 ) on combined therapy , 0.36 mL/min per 1.73 m2 ( IQR : 0.18–0.53 mL/min per 1.73 m2 ) on delapril , and 0.30 mL/min per 1.73 m2 ( IQR : 0.12–0.50 mL/min per 1.73 m2 ) on placebo ( P=0.87 and P=0.53 versus combined therapy or delapril , respectively ) . Similar findings were observed when baseline GFR values were not considered for slope analyses . Albuminuria was stable in the 3 treatment groups . The hazard ratio ( 95 % CI ) for major cardiovascular events between combined therapy and placebo was 0.17 ( 0.04–0.78 ; P=0.023 ) . Among 192 subjects without retinopathy at inclusion , the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 ( 0.07–0.99 ; P=0.048 ) . Among 200 subjects with central ized neurological evaluation , the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 ( 0.24–0.87 ; P=0.017 ) and 0.52 ( 0.27–0.99 ; P=0.048 ) , respectively . Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo ( P=0.03 ) but did not change on combined or delapril therapy . Treatment was well tolerated . In hypertensive type 2 diabetic patients , combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease , retinopathy , and neuropathy and stabilized insulin sensitivity PURPOSE To evaluate the effect of long-term treatment with metoprolol after coronary bypass grafting on death and cardiac events . METHODS Patients in western Sweden on whom coronary artery bypass grafting was performed between June 1988 and June 1991 were evaluated for inclusion during the first 3 weeks after surgery . Major exclusion criteria were age > 75 years , concomitant valve surgery , traditional contraindications to beta-blockers and unwillingness to participate . Patients were r and omized in a double-blind fashion to 100 mg of metoprolol/placebo daily for 2 weeks and thereafter 200 mg daily for 2 years . RESULTS Of 2365 patients who were operated on , 967 were r and omized to either metoprolol ( n = 480 ) or placebo ( n = 487 ) . Primary end points ( death , non-fatal myocardial infa rct ion , unstable angina pectoris , need for coronary artery bypass grafting or percutaneous transluminal angioplasty ) , were reached by 42 patients in the metoprolol group ( 8.8 % ) , as compared with 39 in the placebo group ( 8.0 % ) ( P = 0.73 ) . Of all the patients r and omized to metoprolol , 34 % withdrew from blind treatment prematurely compared with 44 % for placebo ( P < 0.01 ) . CONCLUSION Prophylactic treatment with metoprolol over a 2-year period after coronary artery bypass grafting did not reduce death or the development of cardiac events . However , the 95 % confidence limits ranged from the possibility of a 30 % reduction in events to a 68 % increase in events if patients were treated with metoprolol as compared with placebo Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril  reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events  . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths 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 % 
    Output:
    