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: CONTEXT Individuals with diabetes are at increased risk for cardiovascular disease ( CVD ) , but more aggressive targets for risk factor control have not been tested . OBJECTIVE To compare progression of sub clinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol ( LDL-C ) of 70 mg/dL or lower and systolic blood pressure ( SBP ) of 115 mm Hg or lower vs st and ard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , blinded-to-end point , 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma , Arizona , and South Dakota . Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events . INTERVENTIONS Participants were r and omized to aggressive ( n=252 ) vs st and ard ( n=247 ) treatment groups with stepped treatment algorithms defined for both . MAIN OUTCOME MEASURES Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT ) . Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events . RESULTS Mean target LDL-C and SBP levels for both groups were reached and maintained . Mean ( 95 % confidence interval ) levels for LDL-C in the last 12 months were 72 ( 69 - 75 ) and 104 ( 101 - 106 ) mg/dL and SBP levels were 117 ( 115 - 118 ) and 129 ( 128 - 130 ) mm Hg in the aggressive vs st and ard groups , respectively . Compared with baseline , IMT regressed in the aggressive group and progressed in the st and ard group ( -0.012 mm vs 0.038 mm ; P < .001 ) ; carotid arterial cross-sectional area also regressed ( -0.02 mm(2 ) vs 1.05 mm(2 ) ; P < .001 ) ; and there was greater decrease in left ventricular mass index ( -2.4 g/m(2.7 ) vs -1.2 g/m(2.7 ) ; P = .03 ) in the aggressive group . Rates of adverse events ( 38.5 % and 26.7 % ; P = .005 ) and serious adverse events ( n = 4 vs 1 ; P = .18 ) related to blood pressure medications were higher in the aggressive group . Clinical CVD events ( 1.6/100 and 1.5/100 person-years ; P = .87 ) did not differ significantly between groups . CONCLUSIONS Reducing LDL-C and SBP to lower targets result ed in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes . Clinical events were lower than expected and did not differ significantly between groups . Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047424 BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P<0.001 ) and angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P<0.001 ) ; the rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P<0.001 ) , syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P<0.001 ) . CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . ) The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter study which will be conducted in some 20 countries world-wide . Two major issues will be investigated : i ) What is the optimal target diastolic blood pressure during antihypertensive treatment with regard to the reduction in cardiovascular morbidity and mortality ? In order to address this question patients will be r and omized to three different therapeutic goals : a diastolic blood pressure < or = 90 mmHg , < or = 85 mmHg or < or = 80 mmHg ; ii ) The second aim is to evaluate the effect of a low dose acetylsalicylic acid ( ASA , aspirin ) 75 mg o.d . in comparison with placebo on cardiovascular morbidity and mortality . The first aim will be investigated in accordance with the PROBE design ( Prospect i ve R and omized Open Blinded Endpoint evaluation ) , whereas the evaluation of aspirin versus placebo will be conducted under double blind conditions . It is estimated that 1,100 clinical events will be needed in order to answer the question regarding the relationship between target diastolic blood pressure and major cardiovascular events . The collection of these events will require the enrollment of at least 18,000 hypertensive men and women aged 50 - 80 years to be followed for 2.5 years ( about 40,000 patient years ) . All patients will be given felodipine 5 mg o.d . as basic antihypertensive treatment with the addition of a beta-blocker or an ACE-inhibitor in a second step , with further predetermined increments in dosage as required in order to obtain the r and omized therapeutic goal The objective of this study was to investigate the relationship between  hypertension and risk of stroke in the elderly . The study was performed within the framework of the Rotterdam Study , a prospect i ve population -based cohort study . The risk of first-ever stroke was associated with hypertension ( relative risk , 1.6 ; 95 % CI , 1.2 to 2.0 ) and with isolated systolic hypertension ( relative risk , 1.7 ; 95 % CI , 1.1 to 2.6 ) . We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects . In treated subjects , we found a J-shaped relation between blood pressure and the risk of stroke . In the lowest category of diastolic blood pressure , the increase of stroke risk was statistically significant compared with the reference category . Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly . The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of " the lower the better " is not the optimal strategy in the elderly OBJECTIVES The study evaluated the risk of cardiovascular mortality according to combined spontaneous ( non-treatment-related ) changes in both systolic and diastolic blood pressure ( BP ) . BACKGROUND Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations . METHODS Two independent French male cohorts were studied : the IPC cohort ( Investigations Préventives et Cliniques ) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart , and the Paris Prospect i ve Study composed of 6,246 men aged 42 to 53 years , examined annually for a period of four years . None of the subjects were taking antihypertensive medication . Annual changes in BP were estimated , and subjects were divided into groups according to the increase , lack of change , or decrease of systolic or diastolic BP . Nine groups were formed by combining the changes of systolic and diastolic BP . Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospect i ve Study . RESULTS In both cohorts , after adjustment for age and major risk factors , the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP ( relative risk : 2.07 [ 1.05 to 4.06 ] in the IPC Study and 2.16 [ 1.16 to 4.01 ] in the Paris Prospect i ve Study ) . CONCLUSIONS Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk . Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neurop 
    Output:
    
agent
Treating patients to lower than st and ard BP targets , < /=140 - 160/90 - 100 mmHg , does not reduce mortality or morbidity .
***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: CONTEXT Individuals with diabetes are at increased risk for cardiovascular disease ( CVD ) , but more aggressive targets for risk factor control have not been tested . OBJECTIVE To compare progression of sub clinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol ( LDL-C ) of 70 mg/dL or lower and systolic blood pressure ( SBP ) of 115 mm Hg or lower vs st and ard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , blinded-to-end point , 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma , Arizona , and South Dakota . Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events . INTERVENTIONS Participants were r and omized to aggressive ( n=252 ) vs st and ard ( n=247 ) treatment groups with stepped treatment algorithms defined for both . MAIN OUTCOME MEASURES Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT ) . Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events . RESULTS Mean target LDL-C and SBP levels for both groups were reached and maintained . Mean ( 95 % confidence interval ) levels for LDL-C in the last 12 months were 72 ( 69 - 75 ) and 104 ( 101 - 106 ) mg/dL and SBP levels were 117 ( 115 - 118 ) and 129 ( 128 - 130 ) mm Hg in the aggressive vs st and ard groups , respectively . Compared with baseline , IMT regressed in the aggressive group and progressed in the st and ard group ( -0.012 mm vs 0.038 mm ; P < .001 ) ; carotid arterial cross-sectional area also regressed ( -0.02 mm(2 ) vs 1.05 mm(2 ) ; P < .001 ) ; and there was greater decrease in left ventricular mass index ( -2.4 g/m(2.7 ) vs -1.2 g/m(2.7 ) ; P = .03 ) in the aggressive group . Rates of adverse events ( 38.5 % and 26.7 % ; P = .005 ) and serious adverse events ( n = 4 vs 1 ; P = .18 ) related to blood pressure medications were higher in the aggressive group . Clinical CVD events ( 1.6/100 and 1.5/100 person-years ; P = .87 ) did not differ significantly between groups . CONCLUSIONS Reducing LDL-C and SBP to lower targets result ed in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes . Clinical events were lower than expected and did not differ significantly between groups . Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047424 BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P<0.001 ) and angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P<0.001 ) ; the rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P<0.001 ) , syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P<0.001 ) . CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . ) The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter study which will be conducted in some 20 countries world-wide . Two major issues will be investigated : i ) What is the optimal target diastolic blood pressure during antihypertensive treatment with regard to the reduction in cardiovascular morbidity and mortality ? In order to address this question patients will be r and omized to three different therapeutic goals : a diastolic blood pressure < or = 90 mmHg , < or = 85 mmHg or < or = 80 mmHg ; ii ) The second aim is to evaluate the effect of a low dose acetylsalicylic acid ( ASA , aspirin ) 75 mg o.d . in comparison with placebo on cardiovascular morbidity and mortality . The first aim will be investigated in accordance with the PROBE design ( Prospect i ve R and omized Open Blinded Endpoint evaluation ) , whereas the evaluation of aspirin versus placebo will be conducted under double blind conditions . It is estimated that 1,100 clinical events will be needed in order to answer the question regarding the relationship between target diastolic blood pressure and major cardiovascular events . The collection of these events will require the enrollment of at least 18,000 hypertensive men and women aged 50 - 80 years to be followed for 2.5 years ( about 40,000 patient years ) . All patients will be given felodipine 5 mg o.d . as basic antihypertensive treatment with the addition of a beta-blocker or an ACE-inhibitor in a second step , with further predetermined increments in dosage as required in order to obtain the r and omized therapeutic goal The objective of this study was to investigate the relationship between  hypertension and risk of stroke in the elderly . The study was performed within the framework of the Rotterdam Study , a prospect i ve population -based cohort study . The risk of first-ever stroke was associated with hypertension ( relative risk , 1.6 ; 95 % CI , 1.2 to 2.0 ) and with isolated systolic hypertension ( relative risk , 1.7 ; 95 % CI , 1.1 to 2.6 ) . We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects . In treated subjects , we found a J-shaped relation between blood pressure and the risk of stroke . In the lowest category of diastolic blood pressure , the increase of stroke risk was statistically significant compared with the reference category . Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly . The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of " the lower the better " is not the optimal strategy in the elderly OBJECTIVES The study evaluated the risk of cardiovascular mortality according to combined spontaneous ( non-treatment-related ) changes in both systolic and diastolic blood pressure ( BP ) . BACKGROUND Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations . METHODS Two independent French male cohorts were studied : the IPC cohort ( Investigations Préventives et Cliniques ) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart , and the Paris Prospect i ve Study composed of 6,246 men aged 42 to 53 years , examined annually for a period of four years . None of the subjects were taking antihypertensive medication . Annual changes in BP were estimated , and subjects were divided into groups according to the increase , lack of change , or decrease of systolic or diastolic BP . Nine groups were formed by combining the changes of systolic and diastolic BP . Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospect i ve Study . RESULTS In both cohorts , after adjustment for age and major risk factors , the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP ( relative risk : 2.07 [ 1.05 to 4.06 ] in the IPC Study and 2.16 [ 1.16 to 4.01 ] in the Paris Prospect i ve Study ) . CONCLUSIONS Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk . Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neurop 
    Output:
    