***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 
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    Input: 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 The primary results of a three-year prospect i ve , double-blind , placebo-controlled trial in non-insulin-dependent diabetic ( NIDDM ) patients show that an anti-hypertensive regimen , which includes the ACE inhibitor enalapril , preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors ( J Am Soc Nephrol 3:335 , 1992 ) . The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis . Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [ baseline glomerular filtration rate ( GFR ) 30 to 100 ml/min/1.73 m2 ] . Twenty-four hour urinary excretion of albumin ( UAE ) , protein , urea nitrogen , creatinine and isotopically determined GFR were measured at baseline and six month intervals . Glycemic control and blood pressure regulation were assessed every three months . The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline ( UAE > 300 mg/24 hr ) as compared to patients with baseline sub- clinical proteinuria ( UAE < or = 300 mg/24 hr ) . Antihypertensive treatment with enalapril  preserved GFR significantly better ( P < 0.01 ) in the patients with sub- clinical proteinuria at baseline ( UAE < or = 300 mg/24 hr ) than other antihypertensive treatments which excluded the ACE inhibitor . Furthermore , only 7 % of the enalapril-treated group progressed to clinical albuminuria compared to 21 % of control treated patients . Although the enalapril-treated group had a lower mean blood pressure during the maintenance period , no correlation between blood pressure ( systolic , diastolic or mean arterial ) and rate of change of GFR was observed . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Determine the prevalence of microalbuminuria in patients with type 2 diabetes mellitus ( DM ) in general practice , as an independent risk factor for cardiovascular diseases . DESIGN Prospect i ve , descriptive . METHOD Data were collected on patients with type 2 DM in the Zwolle region of the Netherl and s , all of whom were being treated by their general practitioner . The inclusion period was 1 February 2000 - 31 January 2001 . The study formed part of a larger investigation , in which the albumin concentration in a urine sample and the  albumin-creatinin ratio  were determined once per year . A total of 32 general practitioners took part in the study . RESULTS In the general practice s studied , 2094 patients were known with type 2 DM and 1653 ( 79 % ) were treated exclusively by the general practitioner . Of these 1653 patients , 67 ( 4 % ) were excluded and of the 1586 invited patients remaining , 1441 ( 91 % ) participated .  Microalbuminuria was present in 33 % of the patients and macroalbuminuria in 7 % of the patients , and the prevalences increased with age : < 50 , 50 - 70 and > 70 years . 18 % ( 6/33 ) of the patients aged < 50 years with microalbuminuria were treated with an ACE inhibitor or angiotensin II antagonist compared to 33 % ( 183/548 ) of patients > or = 50 years . 91 % ( 488/539 ) of the patients > or = 50 years with microalbuminuria had hypertension and /or lipid profile abnormalities and 82 % ( 402/488 ) of them were not treated or did not receive adequate treatment for this condition . CONCLUSION Microalbuminuria and macroalbuminuria were present in respectively 33 % and 7 % of the patients with type 2 DM in primary care . The treatment of hypertension and lipid profile abnormalities was often inadequate . Therefore , screening patients aged 50 years and older with type 2 DM for albuminuria is justified Background —The aim of this study was to assess the level of urinary albumin excretion ( microalbuminuria ) , which is associated with increased risk of coronary heart disease and death , in the population . Microalbuminuria has been suggested as an atherosclerotic risk factor . However , the lower cutoff level of urinary albumin excretion is unknown . It is also unknown whether impaired renal function confounds the association . Methods and Results —In the Third Copenhagen City Heart Study in 1992 to 1994 , 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program  , including a timed overnight urine sample . The participants were then followed up prospect ively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death . During follow-up , 109 incident cases of coronary heart disease and 276 deaths were traced . A urinary albumin excretion above the upper quartile , ie , 4.8 μg/min , was associated with increased risk of coronary heart disease ( RR , 2.0 ; 95 % CI , 1.4 to 3.0 ; P < 0.001 ) and death ( RR , 1.9 ; 95 % CI , 1.5 to 2.4 ; P < 0.001 ) independently of age , sex , renal creatinine clearance , diabetes mellitus , hypertension , and plasma lipids . Lower levels of urinary albumin excretion were not associated with increased risk . Conclusions —Microalbuminuria , defined as urinary albumin excretion > 4.8 μg/min ( corresponding to ≈6.4 μg/min during daytime ) , is a strong and independent determinant of coronary heart disease and death . Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies Objective The aim of this open-labelled , r and omised , parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate ( AER ) and left ventricular mass index ( LVMI ) in hypertensive patients with type-2 diabetes and microalbuminuria . Methods After a 4-week wash-out period , 174 patients with essential hypertension [ diastolic blood pressure ( DBP ) > 80 mmHg and < 100 mmHg ] , type-2 diabetes and microalbuminuria were r and omised to manidipine 10 mg o.d . or lisinopril 10 mg o.d . ; after 8 weeks , the dose was doubled in non-responders ( DBP > 80 mmHg ) ; after 3 months , treatment was discontinued in the non-responder patients and in those complaining of side effects ; the remaining 121 patients continued their therapy with manidipine or lisinopril , and 99 completed the 2-year study . At the end of the wash-out period , of the titration period and after 6 , 12 , 18 and 24 months of treatment , BP was measured , AER , creatinine clearance , glycosylated haemoglobin ( HbA1c ) and body mass index ( BMI ) were evaluated and an echocardiographic evaluation was performed . Results The 99 patients who completed the study were statistically analysed according to a per- protocol evaluation . Manidipine and lisinopril  significantly reduced systolic blood pressure ( SBP ) and DBP levels ( at 24 months , −22.3/15.5 mmHg , P<0.001 versus baseline and −21.4/15.7 mmHg , P<0.01 versus baseline , respectively ) . Both drugs provided a significant decrease in AER , but it was significantly more pronounced with lisinopril ( at 24 weeks , −37.2 mg/24 h , P<0.001 versus baseline ) than with manidipine ( –29.9 mg/24 h , P<0.05 versus baseline ) and became evident earlier in the lisinopril group ( after 3 months versus 6 months of treatment ) . Manidipine produced a greater reduction of LVMI than lisinopril ( −14.9 g/m2 versus –10.8 g/m2 at 24 months ) . The effect was more pronounced in patients with left ventricular hypertrophy at baseline ( −19.8 g/m2 versus –12.8 g/m2 , P<0.05 ) . Conclusion These data suggest that , despite similar BP lowering , non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion ( UAE ) in hypertensive patients with type II non-insulin-dependent diabetes mellitus ( NIDDM ) and impaired renal function . A 2-year , prospect i ve , r and omised study was conducted on 51 men with a diastolic blood pressure ( DBP ) ⩾95 and ⩽105 mm Hg , stable NIDDM , serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE > 300 and < 2000 mg/24 h. after a 3-month preliminary observation period , during which patients began a low-protein , low-sodium diet , and a subsequent 4-week run-in period on placebo , patients were r and omly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years . both drugs similarly reduced bp without affecting glucose homeostasis . in the ramipril group uae significantly decreased after only 3 months of treatment , whereas in the nitrendipine group a significant although lesser reduction in uae was observed only after 1 year . during the second year the uae% change was not statistically different between the two treatments . serum creatinine and creatinine clearance showed no significant change with both drugs . the progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups . in conclusion both ramipril and nitrendipine were associated with a decrease in uae although such a reduction was earlier and more marked with ramipril . the decline of renal function did not differ significantly between the two treatments Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models 
    Output:
    
The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria .
A network meta- analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons .
Conclusions /interpretationOur review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs , mainly CCBs , and placebo in type 2 diabetes .
The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect