***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 — Hypertension treatment guidelines recommend that blood pressure ( BP ) be lowered to < 140/90 mm Hg , but that a reduction to < 130/80 mm Hg be adopted in patients at high cardiovascular ( CV ) risk . We investigated the CV and renal benefits associated with these BP targets in the high-CV-risk population of the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial ( ONTARGET ) . Methods and Results — Patients were divided into 4 groups according to the proportion of in-treatment visits before the occurrence of an event ( < 25%–>75 % ) in which BP was reduced to < 140/90 or < 130/80 mm Hg . After adjustment for demographic and clinical variables , a progressive increase in the proportion of visits in which BP was reduced to < 140/90 or < 130/80 mm Hg was associated with a progressive reduction in the risk of stroke , new onset of microalbuminuria or macroalbuminuria , and return to normoalbuminuria in albuminuric patients . An increased frequency of BP control to either target did not have any consistent effect on the adjusted risk of myocardial infa rct ion and heart failure . The adjusted risk of CV events was reduced by increasing the frequency of BP control to < 140/90 mm Hg , but not to < 130/80 mm Hg . Similar findings were obtained for the achievement of the BP target in the visit preceding a CV event . Conclusion — The more frequent achievement of the BP targets recommended by guidelines led to cerebrovascular and renal protection , but did not increase cardiac protection . Overall , CV protection was favorably affected by the less tight but not by the tighter BP target . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00153101 OBJECTIVE Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator – activated receptor-γ2 ( PPAR-γ2 ) Pro12Ala polymorphism . We prospect ively evaluated the association between Pro12Ala polymorphism ( rs1801282 ) and new-onset microalbuminuria . RESEARCH DESIGN AND METHODS Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)—a prospect i ve , r and omized trial evaluating ACE inhibition effect on new-onset microalbuminuria ( albuminuria 20–200 μg/min in at least two of three consecutive overnight urine collection s in two consecutive visits ) in hypertensive type 2 diabetes with albuminuria < 20 μg/min at inclusion . RESULTS Baseline characteristics of Ala ( Ala/Ala or Ala/Pro ) carriers and Pro/Pro homozygotes were similar , with a nonsignificant trend to lower albuminuria ( P = 0.1107 ) in the 177 Ala carriers . Over a median ( interquartile range ) of 44.0 ( 17.1–51.9 ) months , 7 ( 4 % ) Ala carriers and 86 ( 9.1 % ) Pro/Pro homozygotes developed microalbuminuria ( hazard ratio [ HR ] 0.45 [ 95 % CI 0.21–0.97 ] ; P = 0.042 ) . Final albuminuria was significantly lower in Ala carriers than Pro/Pro homozygotes ( 7.3 ± 9.1 vs. 10.5 ± 24.9 μg/min , respectively ) , even after adjustment for baseline albuminuria ( P = 0.048 ) . Baseline and follow-up blood pressure and metabolic control were similar in both groups . Incidence of microalbuminuria was significantly decreased by ACE versus non-ACE inhibitor therapy in Pro/Pro homozygotes ( 6.3 vs. 11.9 % , respectively , HR 0.46 [ 0.29–0.72 ] ; P < 0.001 ) . CONCLUSIONS In type 2 diabetes , the Ala allele protects from worsening albuminuria and new-onset microalbuminuria , and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype . Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy Background —Limited prospect i ve epidemiological data are available on the relation between exposure to Chlamydia pneumoniae , Helicobacter pylori , cytomegalovirus ( CMV ) , and hepatitis A virus ( HAV ) , individually or as a total pathogen score , and human cardiovascular ( CV ) disease . Methods and Results —We analyzed enrollment sera from 3168 Canadian patients in the Heart Outcomes Prevention Evaluation ( HOPE ) study for antibodies to C pneumoniae , H pylori , CMV , and HAV and measured the relation between serostatus and 494 adjudicated trial outcomes of myocardial infa rct ion , stroke , or CV death over 4.5 years of follow-up . CV events were associated with CMV serostatus ( covariate-adjusted hazard ratio [ HR ] , 1.24 ; 95 % CI , 1.01 , 1.53 ) . Neither C pneumoniae IgG ( adjusted HR , 0.87 ; 95 % CI , 0.68 , 1.10 ) , C pneumonia IgA ( adjusted HR , 1.10 ; 95 % CI , 0.90 , 1.34 ) , H pylori IgG ( HR , 0.99 ; 95 % CI , 0.82 , 1.19 ) , nor HAV IgG ( HR , 1.01 ; 95 % CI , 0.83 , 1.24 ) predicted CV events . Total pathogen score was associated with CV events ( adjusted HR for 4 versus 1 or 0=1.41 ; 95 % CI , 1.02 , 1.96 ) . Conclusions —Exposure to CMV but not to C pneumoniae , H pylori , or HAV was associated with a slight excess risk of subsequent myocardial infa rct ion , stroke , or CV death in HOPE study patients , and total pathogen score based on these infections predicted a small increased hazard of CV events BACKGROUND Both hyper- and hypokalemia increase cardiovascular risk . Modest hyperkalemia is common with angiotensin-converting enzyme inhibition . We studied post-hoc the association of an initial , on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9297 individuals at high cardiovascular risk , r and omized to an ACE inhibitor or to placebo .  METHODS Post-hoc analysis of cardiovascular outcomes , as related to serum potassium levels , in the HOPE ( Heart Outcomes and Prevention Evaluation ) study which compared ramipril to placebo , and included 692 patients with a serum potassium level > 5.0 mM and 137 with a serum potassium level < 3.5 mM , defined as hyper- and hypokalemia , respectively .  Serum potassium  was measured 1 month after start of r and omized treatment . RESULTS With hyperkalemia , the primary event rate was unchanged compared to normokalemia ( 15.5 vs 15.7 % , p > 0.4 , respectively ) , with hypokalemia , the primary event rate was higher ( 22.6 % vs 15.5 % , respectively , p = 0.023 ) . The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 ( 1.00 - 2.06 ) on multivariate analysis . The combined primary outcome ( myocardial infa rct ion , cardiovascular death , stroke ) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia . R and omized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo , respectively . The benefit of ramipril on cardiovascular outcomes was independent of serum potassium , but ramipril reduced hypokalemia in the entire cohort ( 1.15 vs 1.86 % with placebo , p = 0.005 ) , particularly in those participants on diuretics ( 3.8 % vs 6.5 % , p = 0.07 ) . CONCLUSIONS In patients at high cardiovascular risk , modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not . Ramipril reduces hypokalemia and decreases risk 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 OBJECTIVE —In patients with type 2 diabetes , left ventricular hypertrophy ( LVH ) predicts cardiovascular events , and the prevention of LVH is cardioprotective . We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic ( ECG ) evidence of LVH ( ECG-LVH ) . RESEARCH DESIGN AND METHODS —This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial ( BENEDICT ) , who had no ECG-LVH at baseline and were r and omly assigned to at least 3 years of blinded ACE inhibition with tr and olapril ( 2 mg/day ) or to non-ACE inhibitor therapy .  Treatment was titrated to systolic/diastolic blood pressure < 130/80 mmHg . ECG readings were central ized and blinded to treatment . RESULTS —Baseline characteristics of the two groups were similar . Over a median ( interquartile range ) follow-up of 36 ( 24–48 ) months , 13 of the 423 patients ( 3.1 % ) receiving tr and olapril compared with 31 of the 376 patients ( 8.2 % ) receiving non-ACE inhibitor therapy developed ECG-LVH ( hazard ratio [ HR ] 0.34 [ 95 % CI 0.18–0.65 ] , P = 0.0012 unadjusted , and 0.35 [ 0.18–0.68 ] , P = 0.0018 adjusted for predefined baseline covariates ) . The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline . Compared with baseline , both Sokolow-Lyon and Cornell voltages significantly decreased with tr and olapril but did not change with non-ACE inhibitor therapy . CONCLUSIONS —ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure – lowering effect . Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes , early ACE inhibition may be 
    Output:
    
There was no significant difference in the risk of cough , headache or hyperkalaemia when ARB was to placebo .
ACEi were found to prevent new onset DKD and death in normoalbuminuric people with diabetes , and could therefore be used in this population .