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Summary The ABCD ( Appropriate Blood Pressure Control in Diabetes ) Trial is a large , prospect i ve , r and omized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) design ed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy , retinopathy , cardiovascular disease , and neuropathy in NIDDM . The secondary objective is to determine equivalency of the effects of a calcium channel blocker ( nisoldipine ) and an angiotensin-converting-enzyme inhibitor ( enalapril ) as a first-line antihypertensive agent in the prevention and /or progression of these diabetic vascular complications . The study consists of two study population s aged 40–74 years , 470 hypertensive patients ( diastolic blood pressure of ≥ 90.0 mmHg at time of r and omization ) and 480 normotensive patients ( diastolic blood pressure of 80.0 mmHg at time of r and omization ) . The study duration is 5 years and is scheduled to end in May of 1998 . Patients are r and omized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy . Patients are also r and omized to nisoldipine or enalapril , with open-label medications added if further blood pressure control is necessary . The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance . Secondary outcome measures are urinary albumin excretion , left ventricular hypertrophy , retinopathy , and neuropathy . Cardiovascular morbidity and mortality will also be evaluated . Given the data showing the impact of hypertension on complications in NIDDM , the ABCD Trial is design ed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM . [ Diabetologia ( 1996 ) 39 : 1646–1654 Essential hypertension is a major Public Health issue . Although the number of treated hypertensive patients has increased , only 25 % of treated patients have their blood pressure levels under control . The benefit of treating hypertension has been proven , but cardiovascular morbidity and mortality rates remain high . The ideal antihypertensive drug should not only normalize blood pressure levels , but also reduce the associated cardiovascular morbidity and mortality rates . The role of angiotensin II in systemic hypertension and its complications has been recently redefined . The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated , especially the role of angiotensin II in left ventricular hypertrophy , vascular hypertrophy , endothelial dysfunction , and congestive heart failure . Of all ongoing mortality and morbidity trials in systemic hypertension , VALUE ( Valsartan Antihypertensive Long-term Use Evaluation ) is the only one comparing an angiotensin II antagonist ( valsartan ) with a third-generation calcium channel blocker ( amlodipine ) . The main hypothesis of the VALUE trial is that , for an equivalent decrease in blood pressure , valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity . VALUE is a prospect i ve , multinational , multicentre , double-blind , r and omized , active-controlled , 2-arm parallel group comparison with a response-dependent dose titration scheme . VALUE involves 14,400 patients in over 30 countries , who will be followed for 4 years or until 1450 patients experience a primary endpoint . The population to be included in VALUE consists of hypertensive men and women , aged 50 years or older , and at a relatively high risk of sustaining a cardiovascular event . The high risk profile is defined taking into account age , gender , and a list of cardiovascular risk factors and disease factors . Risk factors are cigarette smoking , hypercholesterolaemia , diabetes mellitus , uncomplicated left ventricular hypertrophy , proteinuria , and high serum creatinine . Disease factors include documented history of myocardial infa rct ion , peripheral vascular disease , stroke or transient ischaemic attack , or the presence of left ventricular hypertrophy with strain on the ECG . A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients . The trial started on 10 September 1997 OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually Background : The increased risk of cardiovascular morbidity and mortality associated with arterial hypertension is particularly pronounced in patients with type 2 diabetes mellitus .  Blood pressure control is , therefore , decisively important but often not sufficiently achieved . Objective : The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring . Secondary objectives were to evaluate the effects on glycaemic control and urinary albumin excretion as well as adverse effects . Methods : In a multicentre , double-blind , r and omized , placebo-controlled study 119 patients with blood pressure at or above 130/80 mmHg despite triple antihypertensive therapy were included . One tablet of 25 mg spironolactone or placebo was added to previous treatment and increased to two if blood pressure below 130/80 mmHg was not achieved after 4 weeks . Blood pressure was measured by ambulatory monitoring at baseline and after 16 weeks . Results : The study was completed by 112 patients , 57 r and omized to spironolactone  and 55 to placebo .  Average daytime placebo-corrected blood pressure was reduced by 8.9 (4.7–13.2)/3.7 ( 1.5–5.8 ) mmHg . Also office blood pressure , night-time , 24-h and pulse pressures were reduced significantly . Urinary albumin/creatinine ratio was significantly reduced in the spironolactone group . Glycaemic control remained unchanged . Hyperkalemia was the most frequent adverse event leading to dose reduction in three cases and discontinuation in one , whereas gynaecomastia was not reported . Conclusion : Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus Background The benefits of treating hypertension in elderly diabetic patients , in terms of achieving reductions in cardiovascular morbidity and mortality , have been documented in several recent prospect i ve trials . There has , however , been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infa rct ion in this group of patients . Design STOP Hypertension-2 was a prospect i ve , r and omized , open trial with blinded endpoint evaluation . Methods We studied 6614 elderly patients aged 70–84 years ; 719 of them had diabetes mellitus at the start of the study ( mean age 75.8 years ) . Patients were r and omly assigned to one of three treatment strategies : conventional antihypertensive drugs ( diuretics or β-blockers ) , calcium antagonists , or angiotensin converting enzyme ( ACE ) inhibitors . Results Reduction in blood pressure was similar in the three treatment groups of diabetics . The prevention of cardiovascular mortality was also similar ; the frequency of this primary endpoint did not differ significantly between the three groups . There were , however , significantly fewer ( P = 0.025 ) myocardial infa rct ions during ACE inhibitor treatment ( n = 17 ) than during calcium antagonist treatment ( n = 32 ; relative risk 0.51 , 95 % confidence interval 0.28–0.92 ) ; but a ( non-significant ) tendency to more strokes during ACE inhibitor treatment ( n = 34 compared with n = 29 ; relative risk 1.16 , 95 % confidence interval 0.71–1.91 ) . Conclusion Treatment of hypertensive diabetic patients with conventional antihypertensive drugs ( diuretics , β-blockers , or both ) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors BACKGROUND In 1988 , the Systolic Hypertension in China ( Syst-China ) Collaborative Group initiated the placebo-controlled Syst-China trial to investigate whether antihypertensive drug treatment could reduce the incidence of fatal and nonfatal stroke in older Chinese patients with isolated systolic hypertension . OBJECTIVES To explore ( 1 ) whether the benefits of active treatment were evenly distributed across 4 strata , prospect ively defined according to sex and previous cardiovascular complications , and ( 2 ) whether the morbidity and mortality results were influenced by age , level of systolic or diastolic blood pressure ( BP ) , smoking or drinking habits , or diabetes mellitus at enrollment . METHODS Eligible patients had to be 60 years or older with a sitting systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg . After stratification for center , sex , and previous cardiovascular complications , 1253 patients were assigned to active treatment starting with nitrendipine ( 10 - 40 mg/d ) , with the possible addition of captopril ( 12.5 - 50.0 mg/d ) , and /or hydrochlorothiazide ( 12.5 - 50 mg/d ) . In the 1141 control patients , matching placebos were used similarly . RESULTS Male sex , previous cardiovascular complications , older age , higher systolic BP or lower diastolic BP , living in northern China , smoking , and diabetes mellitus significantly and independently increased the risk of 1 or more of the following end points : total or cardiovascular mortality , all fatal and nonfatal cardiovascular end points , all strokes , and all cardiac end points . In the placebo-control group diabetes raised the risk of all end points 2- to 3-fold ( P < or = .05 ) . However , active treatment reduced the excess risk associated with diabetes to a nonsignificant level ( P values ranging from .12-.86 ) except for cardiovascular mortality ( P = .04 ) . Cox regression with adjustments applied for significant covariates suggested that active treatment may reduce total mortality more ( P = .06 ) in women and stroke more ( P = .07 ) in men and that it may provide better protection against cardiac end points in nonsmokers than smokers ( P = .04 ) . Otherwise , the benefits of active treatment were equally manifest , regardless of the enrollment characteristics of the patients , and regardless of whether active treatment consisted of only nitrendipine or of nitrendipine associated with other active drugs . CONCLUSIONS In elderly Chinese patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improved prognosis . The benefit was particularly evident in diabetic patients ; for cardiac end points it tended to be larger in nonsmokers . Otherwise , the benefit of active treatment was not significantly influenced by the characteristics of the patients at enrollment in the trial BACKGROUND The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear . In prespecified analyses , we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients . METHODS As part of the LIFE study , in a double-masked , r and omised , parallel-group trial , we assigned a group of 1195 patients with diabetes , hypertension , and signs of left-ventricular hypertrophy ( LVH ) on electrocardiograms losartan-based or atenolol-based treatment . Mean age of patients was 67 years ( SD 7 ) and mean blood pressure 177/96 mm Hg ( 14/10 ) after placebo run-in . We followed up patients for at least 4 years ( mean 4.7 years [ 1.1 ] ) . We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality ( cardiovascular death , stroke , or myocardial infa rct ion ) . FINDINGS Mean blood pressure fell to 146/79 mm Hg ( 17/11 ) in losartan patients and 148/79 mm Hg ( 19/11 ) in atenolol patients . The primary endpoint occurred in 103 patients assigned losartan ( n=586 ) and 139 assigned atenolol ( n=609 ) ; relative risk 0.76 ( 95 % CI 0.58-.98 ) , p=0.031 . 38 and 61 patients in the losartan and atenolol groups , respectively , died from cardiovascular disease ; 0.63 ( 0.42 - 0.95 ) , p=0.028 . Mortality from all causes was 63 and 104 in losartan and atenolol groups , respectively ; 0.61 ( 0.45 - 0.84 ) , p=0.002 . INTERPRETATION Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension , diabetes , and LVH . Losartan seems to have benefits beyond blood pressure reduction BACKGROUND Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus , it remains uncertain whether microalbuminuria and /or gross proteinuria are independent risk factors for cardiovascular mortality . Moreover , the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US population s. OBJECTIVE To estimate the relative risks ( RRs ) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus . METHODS We conducted a prospect i ve cohort study of 840 people with older-onset diabetes mellitus who provided urine sample s in the 1984 - 1986 examination of a population -based study of diabetic persons . The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip . The main outcome was time to mortality from cardiovascular disease , as determined from death certificates . RESULTS Of the 840 older-onset diabetic persons , 54.8 % had normoalbuminuria , while 24.8 % had microalbuminuria and 20.5 % had gross proteinuria . During the 12-year follow-up ( 6127 person-years ) , we identified 364 deaths from cardiovascular disease . Compared with persons with normoalbuminuria , those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality . The RR as controlled for age , sex , glycemic control , insulin use , alcohol intake , physical activity , cardiovascular disease history , antihypertensive use , and retinopathy severity , was 1.84 ( 95 % confidence interval [ CI ] , 1.42 - 2.40 ) for those with microalbuminuria and 2.61 ( 95 % CI , 1.99 - 3.43 ) for those with gross proteinuria . Further adjustment for other factors did not change the relations we found . When the end point used was mortality from coronary heart disease , stroke , or all causes , the increased risks were significant for both microalbuminuria ( adjusted RRs [ 95 % CIs ] , 1.96 [ 1.42 - 2.72 ] , 2.20 [ 1.29 - 3.75 ] , and 1.68 [ 1.35 - 2.09 ] , respectively ) and gross proteinuria ( adjusted RRs [ 95 % CIs ] , 2.73 [ 1.95 - 3.81 ] , 2.33 [ 1.28 - 4.24 ] , and 2.47 [ 1.97 - 3.10 ] , respectively ) . CONCLUSIONS Results from our population -based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular , cerebrovascular , and coronary heart diseases . These associations were independent of known cardiovascular risk factors and diabetes-related variables OBJECTIVE The primary objective of the ABCD ( Appropriate Blood Pressure Control in Diabetes ) Trial is to determine the efficacy of intensive versus moderate antihypertensive control on the outcome of type II diabetic end-organ complications in normotensive and hypertensive population s. The secondary objective is to determine whether any differential effect on end-organ complications exists between an angiotensin converting enzyme inhibitor ( enalapril ) and a calcium channel blocker ( nisoldipine ) . DESIGN The ABCD Trial is a prospect i ve , controlled , r and omized , double-blind trial , with a planned follow-up of 5 years . SETTING All patients are seen at the Colorado Prevention Center , site of the ABCD Trial , for follow-up visits . PATIENTS Patients are type II diabetic males and females between the ages of 40 and 74 years with entry diastolic blood pressures > or = 80 mmHg . Patients were recruited from University of Colorado-affiliated hospitals , several health maintenance organizations , and mailing lists from the Colorado affiliate of the American Diabetes Association . INTERVENTIONS Patients were r and omized to intensive antihypertensive drug therapy or moderate antihypertensive drug therapy . Patients were also r and omized to nisoldipine or enalapril , with open-label medications added if further blood pressure control was necessary . MAIN OUTCOME MEASURES The primary outcome measure is glomerular filtration rate as assessed by 24-hour creatinine clearance . Secondary outcome measures are microalbumin urinary excretion , left ventricular hypertrophy , retinopathy , and neuropathy . Cardiovascular morbidity and mortality will also be evaluated . CONCLUSION Given the data showing the impact of hypertension on diabetic complications , the ABCD Trial was design ed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of these complications . Results from the ABCD Trial are expected to lend interpretable and clinical ly relevant findings with regards to the treatment of hypertension in type II diabetes Background : First Nations people with diabetes mellitus and hypertension are at greater risk of renal and cardiovascular complications than are non-native patients because of barriers to health care services . We conducted this r and omized controlled trial to assess whether a community-based treatment strategy implemented by home care nurses would be effective in controlling hypertension in First Nations people with existing hypertension and type 2 diabetes . Methods : We compared 2 community-based strategies for controlling hypertension in First Nations people with existing hypertension and diabetes . In the intervention group , a home care nurse followed a predefined treatment algorithm of pharmacologic antihypertensive therapy . In the control group , treatment decisions were made by each subject 's primary care physician . The primary outcome measure was the difference between the 2 groups in the change in systolic blood pressure after 12 months . Secondary outcome measures were the change in diastolic blood pressure over time , the change in urine albumin status and the incidence of adverse events . Results : Both groups experienced a significant reduction in systolic blood pressure by the final visit ( by 24.0 [ st and ard deviation ( SD ) 13.5 ] mm Hg in the intervention group and by 17.0 [ SD 18.6 ] mm Hg in the control group ) ; p < 0.001 in each case ) . However , the difference between the 2 groups in this change was not significant . Patients in the intervention group had a larger decrease in diastolic blood pressure over time than did those in the control group ( by 11.6 [ SD 10.6 ] mm Hg v. 6.8 [ SD 11.1 ] mm Hg respectively ; p = 0.05 ) . The groups did not differ significantly in terms of changes in urine albumin excretion or incidence of adverse events . Interpretation : High rates of blood pressure control in the community were achieved in both groups in the DREAM 3 study . The addition of a home care nurse to implement a treatment strategy for blood pressure control was more effective in lowering diastolic than systolic blood pressure compared with home care visits for blood pressure monitoring alone and follow-up treatment by a family physician Objective The Captopril Prevention Project ( CAPPP ) was design ed as a prospect i ve intervention trial comparing the effect of a treatment based on the angiotensin-converting enzyme ( ACE ) inhibitor captopril with that of a conventional diuretic and /or β-blocker-based therapy , in 10 985 hypertensive patients . There was no difference in the primary cardiovascular morbidity and mortality endpoint . A lower incidence of diabetes mellitus during captopril treatment was observed in the whole CAPPP cohort that was non-diabetic at baseline ( n = 10 413 ) as well as in such CAPPP patients that were previously untreated ( n = 5033 ) . Methods and results A multivariate analysis of variables associated with the risk of developing diabetes in CAPPP demonstrated that glucose , body mass index ( BMI ) , haemoglobin ( Hb ) , age , ‘ SBP × Untreated ’ ( the interaction between systolic blood pressure at baseline and newly diagnosed hypertension ) , cholesterol and prior antihypertensive treatment came out as risk factors . Based on these factors , a risk score for development of diabetes was calculated for all non-diabetic patients , who were divided into tertiles . For each tertile of risk , captopril therapy was associated with a reduced risk of diabetes development compared with conventional diuretic and /or β-blocker therapy . When the non-diabetic cohort was divided into two subcohorts ; previously treated and previously untreated patients , it turned out that the risk factors for developing diabetes differed between these two subcohorts . Only glucose , BMI and Hb came out as risk factors in all analysed cohorts . Conclusion A captopril-based antihypertensive treatment regimen is associated with a lower risk of diabetes development , compared with conventional therapy based on diuretics and /or β-blockers Antihypertensive therapy reduces the incidence of cardiovascular events in people with diabetes mellitus ( DM ) . However , the effects of treatment on sub clinical atherosclerosis are less well studied . Results of a post hoc cohort analysis of the association between antihypertensive treatment and carotid artery intima-media thickness ( CIMT ) in the Troglitazone Atherosclerosis Regression Trial ( TART ) , a r and omized trial design ed to evaluate the impact of troglitazone treatment on CIMT progression in adults with insulin-requiring type 2 DM , are reported . CIMT , blood pressure ( BP ) , and use of antihypertensive agents  were measured throughout the 2-year treatment period . In multivariable mixed-effects models , the annual rate of change in CIMT in relation to BP and duration of antihypertensive agent use , adjusting for covariates , was evaluated . Higher systolic BP was associated with a higher CIMT progression rate ( p=0.03 ) . This association was reduced by antihypertensive treatment in a duration -dependent manner ( p for interaction=0.035 ) . Adjustment for age , treatment assignment , and change in fasting glucose during the trial did not attenuate these associations . In conclusion , regular use of antihypertensive agents reduces the harmful impact of increased BP on atherosclerosis progression in patients with DM . The antiatherogenic effect of antihypertensive agents , including BP normalization and possible direct vascular wall protection , can be detected by CIMT progression using B-mode ultrasound in patients with DM Objective To compare the effects of two antihypertensive treatment strategies for the prevention of coronary heart disease and other cardiovascular events in the large sub population ( n = 5137 ) with diabetes mellitus in the blood pressure-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial . Methods Patients had either untreated hypertension or treated hypertension . For those with type II diabetes mellitus , inclusion criteria required at least two additional risk factors . Patients were r and omized to amlodipine with addition of perindopril as required ( amlodipine-based ) or atenolol with addition of thiazide as required ( atenolol-based ) . Therapy was titrated to achieve a target blood pressure of less than 130/80 mmHg . Results The trial was terminated early due to significant benefits on mortality and stroke associated with the amlodipine-based regimen . In patients with diabetes mellitus , the amlodipine-based treatment reduced the incidence of the composite endpoint – total cardiovascular events and procedures – compared with the atenolol-based regimen ( hazard ratio 0.86 , confidence interval 0.76–0.98 , P = 0.026 ) . Fatal and nonfatal strokes were reduced by 25 % ( P = 0.017 ) , peripheral arterial disease by 48 % ( P = 0.004 ) and noncoronary revascularization procedures by 57 % ( P < 0.001 ) . For the other endpoints included in the composite , the endpoint differences were less clear including coronary heart disease deaths and nonfatal myocardial infa rct ions ( the primary endpoint ) , which were reduced nonsignificantly by 8 % ( hazard ratio 0.92 , confidence interval 0.74–1.15 ) . Conclusion In the large diabetic subgroup in the blood pressure-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial , the benefits of amlodipine-based treatment , compared with atenolol-based treatment , on the incidence of total cardiovascular events and procedures was significant ( 14 % reduction ) and similar to that observed in the total trial population ( 16 % reduction ) Background Diabetes has long been recognised as a strong , independent risk factor for cardiovascular disease , a problem which accounts for approximately 70 % of all mortality in people with diabetes . Prospect i ve studies show that compared to their non-diabetic counterparts , the relative risk of cardiovascular mortality for men with diabetes is two to three and for women with diabetes is three to four . The two biggest trials in type 2 diabetes , the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) and the University Group Diabetes Program ( UGDP ) study did not reveal a reduction of cardiovascular endpoints through improved metabolic control . Theoretical benefits of the peroxisome proliferator activated receptor gamma ( PPAR-gamma ) activator rosiglitazone on endothelial function and cardiovascular risk factors might result in fewer macrovascular disease events in people with type 2 diabetes mellitus . Objectives To assess the effects of rosiglitazone in the treatment of type 2 diabetes . Search methods Studies were obtained from computerised search es of MEDLINE , EMBASE and The Cochrane Library . Selection criteria Studies were included if they were r and omised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 24 weeks . Data collection and analysis Two authors independently assessed trial quality and extracted data . Pooling of studies by means of fixed-effects meta- analysis could be performed for adverse events only . Main results Eighteen trials which r and omised 3888 people to rosiglitazone treatment were identified . Longest duration of therapy was four years with a median of 26 weeks . Published studies of at least 24 weeks rosiglitazone treatment in people with type 2 diabetes mellitus did not provide evidence that patient-oriented outcomes like mortality , morbidity , adverse effects , costs and health-related quality of life are positively influenced by this compound . Metabolic control measured by glycosylated haemoglobin A1c ( HbA1c ) as a surrogate endpoint did not demonstrate clinical ly relevant differences to other oral antidiabetic drugs . Occurrence of oedema was significantly raised ( OR 2.27 , 95 % confidence interval ( CI ) 1.83 to 2.81 ) . The single large RCT ( ADOPT - A Diabetes Outcomes Progression Trial ) indicated increased cardiovascular risk . New data on raised fracture rates in women reveal extensive action of rosiglitazone in various body tissues . Authors ' conclusions New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy . Safety data and adverse events of all investigations ( published and unpublished ) should be made available to the public OBJECTIVE The Captopril Prevention Project ( CAPPP ) evaluated the effects of an ACE inhibitor-based therapeutic regimen on  cardiovascular mortality and morbidity in hypertension .  One planned sub analysis of the CAPPP was to evaluate the outcome in the diabetic patient group . RESEARCH DESIGN AND METHODS In the CAPPP , 572 ( 4.9 % of 10,985 hypertensive patients ) had diabetes at baseline and were studied according to a prospect i ve , r and omized , open , blinded , end point trial design . Patients aged 25 - 66 years with diastolic blood pressure > or = 100 mmHg were included and r and omized to receive either captopril or conventional antihypertensive treatment ( diuretics and /or beta-blockers ) . RESULTS The primary end point , fatal and nonfatal myocardial infa rct ion and stroke as well as other cardiovascular deaths , was markedly lower in the captopril than in the conventional therapy group ( relative risk [ RR ] = 0.59 ; P = 0.018 ) . Specifically , cardiovascular mortality , defined as fatal stroke and myocardial infa rct ion , sudden death , and other cardiovascular death , tended to be lower in the captopril group ( RR = 0.48 ; P = 0.084 ) , and no difference was observed between the study groups for stroke ( RR = 1.02 ; P = 0.96 ) . Myocardial infa rct ions were less frequent in the captopril group than in the conventional therapy group ( RR = 0.34 ; P = 0.002 ) . Furthermore , total mortality was lower in the captopril as compared with the conventional therapy group ( RR = 0.54 ; P = 0.034 ) . Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor-based therapy . CONCLUSIONS Captopril is superior to a diuretic/beta-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients , especially in those with metabolic decompensation 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 Aims /hypothesisThe Anglo – Danish – Dutch study of intensive treatment in people with screen-detected diabetes in primary care ( ADDITION ) is a pragmatic r and omised controlled trial of the effectiveness of intensified multi-factorial treatment on 5 year cardiovascular morbidity and mortality rates in people with screen-detected type 2 diabetes in the Netherl and s , UK and Denmark . This paper describes the baseline characteristics of the study population , their estimated risk of coronary heart disease and the extent to which that risk is potentially modifiable . Methods Stepwise screening strategies were performed using risk question naires and routine general practice data plus r and om blood glucose , HbA1c and fasting blood glucose measurement . Diabetes was diagnosed using the 1999 World Health Organization criteria and estimated 10 year coronary heart disease risk was calculated using the UK Prospect i ve Diabetes Study risk engine . Results Between April 2001 and December 2006 , 3,057 people with screen-detected diabetes were recruited to the study ( mean age 59.7 years , 58 % men ) after a stepwise screening programme involving 76,308 people screened in 334 general practice s in three countries . Their median estimated 10 year risk of coronary heart disease was 11 % in women ( interquartile range 7–16 % ) and 21 % ( 15–30 % ) in men . There were differences in the distribution of risk factors by country , linked to differences in approaches to screening and the extent to which risk factors had already been detected and treated . The mean HbA1c at recruitment was 7.0 % ( SD 1.6 % ) . Of the people recruited , 73 % had a blood pressure ≥140/90 and of these 58 % were not on antihypertensive medication . Cholesterol levels were above 5.0 mmol/l in 70 % of participants , 91 % of whom were not being treated with lipid-lowering drugs . Conclusions /interpretationPeople with type 2 diabetes detected by screening and included in the ADDITION study have a raised and potentially modifiable risk of CHD . Clinical Trials.gov ID no. : NCT 00237549 Whole-day ambulatory blood pressure monitoring is used to confirm the diagnosis of hypertension and assess the response to antihypertensive therapy .  Neither of these has been applied to patients with type II diabetes mellitus , in whom it has been proposed that the desirable blood pressure should be lower than in nondiabetics . This multicenter study was design ed to examine whether there are differences in the efficacy of a first-line antihypertensive drug when assessed by casual and ambulatory blood pressure determinations in patients with type II diabetes mellitus in whom 24-hour ambulatory monitoring confirms or fails to confirm the diagnosis of hypertension . Forty-three patients ( mean age , 57.7 years ) with stable type II diabetes mellitus and mild hypertension ( casual diastolic pressure , 90 to 104 mm Hg on at least two visits ) were treated with an angiotensin-converting enzyme inhibitor ( benazepril , 10 to 20 mg , once a day ) for 8 weeks . Antihypertensive drug efficacy was assessed by casual ( trough ) and 24-hour ambulatory blood pressure monitoring . Diabetic patients were classified as nonconfirmed hypertensive if the mean 24-hour ambulatory diastolic pressure was below 85 mm Hg . Antihypertensive treatment significantly decreased both systolic and diastolic pressures when determined by either casual measurement ( from a mean of 162.7/98.0 to 153.9/89.2 mm Hg ; P < .001 ) or ambulatory monitoring ( from a mean of 143.1/84.4 to 137.0/81.5 mm Hg ; P < .05 ) . Twenty-one patients ( 49 % ) were classified as confirmed hypertensive and 22 as nonconfirmed hypertensive . In confirmed hypertensive patients benazepril significantly reduced systolic and diastolic pressures when assessed by either casual or 24-hour ambulatory monitoring . ( ABSTRACT TRUNCATED AT 250 WORDS A LARGE , prospect i ve , r and omized clinical trial has been launched to examine the role of hypertension in the complications associated with type II diabetes mellitus involving the kidney , eye , and cardiovascular and neurological systems . This clinical trial is named the Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial . There is considerable epidemiological evidence for the importance of hypertension as a contributing factor for the development and progression of cardiovascular , renal , eye , and neurological complications of both type I ( insulin-dependent ) and type II ( non-insulindependent ) diabetes . There is a progressive increase in the prevalence of hypertension in type I and type II diabetes that correlates with the occurrence of diabetic nephropathy . It is also known that the occurrence of microalbuminuria ( 30 to 259 mg/d ) in type I diabetes is associated with an increase in blood pressure , which , albeit still within the normal range , is higher than diabetic patients without micro albuminuria ( 30 years ) without diabetic complications are nearly always normotensive.4 Epidemiological studies have also shown that mortality rates are fourfold greater among diabetic patients with systolic blood pressures greater than 160 mm Hg.5 Ageadjusted death rates  among Pima Indians have been found to be increased threefold when hypertension is present . The definitive role of hypertension in contributing to the occurrence of the spectrum of microangiopathies of the eye , kidney , and cardiovascular and neurological systems in type II diabetes mellitus , has not been previously examined in a large , prospect i ve , r and omized clinical trial . This is in contrast to the many studies examining the effect of blood sugar control on the progression of diabetic complications primarily in type I diabetes.14 There are several interventional studies in type I diabetes in which antihypertensive therapy has been shown to afford a beneficial effect on renal function . 15·18 The absence of interventional hypertension clinical trials in the type II diabetic population is rather remarkable , since substantial epidemiological evidence exists to support the relationship between hypertension and the spectrum of diabetic complications . Moreover , more than 90 % of diabetic patients in this country have type II diabetes . The specific epidemiological evidence for hypertension as a factor in the cardiovascular , renal , eye , and neurological complications of both type I and type II diabetes will now be briefly discussed BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events Hypertension is increasingly common with advancing age and a risk factor for all kinds of cardiovascular complications . Moreover , cardiovascular disease is a major cause of morbidity and mortality in the elderly . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was set up by the Swedish Hypertension Society to investigate the value of antihypertensive treatment in the elderly . In this placebo controlled r and omised prospect i ve study 1,627 men and women aged 70 - 84 years with a supine blood pressure > or = 180/105 mmHg ( and /or ) but not isolated systolic hypertension participated . Three beta-blockers and one diuretic were used as blood pressure lowering agents and the average follow-up in the study was 25 months ( 3,390 patient-years ) . Administration of active antihypertensive therapy , reduced supine blood pressure from 195/102 mmHg to 167/87 mmHg at longest follow-up in comparison with placebo . A majority of the patients needed combined treatment to reach the goal blood pressure ( 160/95 mmHg ) . Associated with a fall in blood pressure were significant reductions in all cardiovascular primary endpoints ( -40 % , p = 0.0031 ) , in fatal and non-fatal stroke ( -47 % , p = 0.0081 ) and in total mortality ( -43 % , p = 0.0079 ) . In addition to the substantial effects on primary endpoints active treatment also showed clinical ly relevant effects on secondary endpoints ( e.g. heart failure ) . The impact on cardiovascular morbidity and mortality with antihypertensive treatment in this elderly cohort was greater than previously seen in middle-aged hypertensive patients , with maintained tolerability and a favourable cost-effectiveness ratio . Finally , women benefited from treatment at least as much as men CONTEXT Despite nutrition information and guidelines that advise against depriving diabetic patients of the potential benefit of moderate alcohol intake against cardiovascular events , the association between alcohol consumption and risk of cardiovascular outcomes in diabetic individuals has not been determined . OBJECTIVE To examine the relationship between alcohol intake and coronary heart disease ( CHD ) mortality in persons with older-onset diabetes . DESIGN Population -based , prospect i ve cohort study conducted from 1984 through 1996 , with a follow-up of up to 12.3 years . SETTING AND PARTICIPANTS A total of 983 older-onset diabetic individuals ( mean [ SD ] age , 68.6 [ 11.0 ] years ; 45.2 % male ; 98.5 % white ) were interviewed about their past-year intake of alcoholic beverages during the 1984 - 1986 follow-up examination of a population -based study of diabetic persons in southern Wisconsin . MAIN OUTCOME MEASURE Time to mortality from CHD by category alcohol intake . RESULTS Alcohol use was inversely associated with risk of CHD mortality in older-onset diabetic subjects . The CHD mortality rates for never and former drinkers were 43.9 and 38.5 per 1000 person-years , respectively , while the rates for those with alcohol intakes of less than 2 , 2 to 13 , and 14 or more g/d were 25.3 , 20.8 , and 10.0 per 1000 person-years , respectively . Compared with never drinkers and controlling for age , sex , cigarette smoking , glycosylated hemoglobin level , insulin use , plasma C-peptide level , history of angina or myocardial infa rct ion , digoxin use , and the presence and severity of diabetic retinopathy , former drinkers had a relative risk ( RR ) of 0.69 ( 95 % confidence interval [ CI ] , 0.43 - 1.12 ) ; for those who drank less than 2 g/d ( less frequent than 1 drink a week ) , the RR was 0.54 ( 95 % CI , 0.33 - 0.90 ) ; for 2 to 13 g/d , it was 0.44 ( 95 % CI , 0.23 - 0.84 ) ; and for 14 or more g/d ( about 1 drink or more a day ) , it was 0.21 ( 95 % CI , 0.09 - 0.48 ) . Further adjustments for blood pressure , body mass index , education , physical activity , diabetes duration , hypertension history , overt nephropathy , peripheral neuropathy , lipid measures , or intake of medications such as aspirin and antihypertensive agents did not change the associations observed . CONCLUSION Our results suggest an overall beneficial effect of alcohol consumption in decreasing the risk of death due to CHD in people with older-onset diabetes The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized OBJECTIVE The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) Blood Pressure Trial reported no differences in most cardiovascular disease ( CVD ) outcomes between intensive and st and ard blood pressure therapy in individuals with diabetes mellitus ( DM ) and hypertension . Many such individuals are central ly obese . Here we evaluate whether the trial outcomes varied by the level of central obesity . RESEARCH DESIGN AND METHODS The cohort included 4,687 people ( 47.7 % women ) with DM and hypertension . Mean age was 62.2 , and mean follow-up was 4.7 years . Participants were r and omly assigned to one of two blood pressure treatment strategies : intensive ( systolic < 120 mmHg ) or st and ard ( systolic < 140 mmHg ) . Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity . The primary ACCORD outcome ( a composite of nonfatal myocardial infa rct ion [ MI ] , nonfatal stroke , or CVD death ) and three secondary outcomes ( nonfatal MI , fatal or nonfatal stroke , and CVD death ) were examined using proportional hazard models . RESULTS There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes ( P > 0.25 in all cases ) . Controlling for waist-to-height quartile had no significant impact on previously published results for  intensive blood pressure therapy .  Waist-to-height ratio was significantly related to CVD mortality ( hazard ratio 2.32 [ 95 % CI 1.40–3.83 ] , P = 0.0009 comparing the heaviest to lightest quartiles ) , but not to the other outcomes ( P > 0.09 in all cases ) . CONCLUSIONS Intensive lowering of blood pressure versus st and ard treatment does not ameliorate CVD risk in individuals with DM and hypertension . These results did not vary by quartile of waist-to-height ratio Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment . Design One year open label active treatment extension of r and omised controlled trial ( Hypertension in the Very Elderly Trial ( HYVET ) ) . Setting Hospital and general practice based centres mainly in eastern and western Europe , China , and Tunisia . Participants People on double blind treatment at the end of HYVET were eligible to enter the extension . Interventions Participants on active blood pressure lowering treatment continued taking active drug ; those on placebo were given active blood pressure lowering treatment . The treatment regimen was as used in the main trial — indapamide SR 1.5 mg ( plus perindopril 2 - 4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg . Main outcome measures The primary outcome was all stroke ; other outcomes included total mortality , cardiovascular mortality , and cardiovascular events . Results Of 1882 people eligible for entry to the extension , 1712 ( 91 % ) agreed to participate . During the extension period , 1682 patient years were accrued . By six months , the difference in blood pressure between the two groups was 1.2/0.7 mm Hg . Comparing people previously treated with active drug and those previously on placebo , no significant differences were seen for stroke ( n=13 ; hazard ratio 1.92 , 95 % confidence interval 0.59 to 6.22 ) or cardiovascular events ( n=25 ; 0.78 , 0.36 to 1.72 ) . Differences were seen for total mortality ( 47 deaths ; hazard ratio 0.48 , 0.26 to 0.87 ; P=0.02 ) and cardiovascular mortality ( 11 deaths ; 0.19 , 0.04 to 0.87 ; P=0.03 ) . Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment . Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment . Trial registration Clinical trials NCT00122811 AIMS To examine the scope for cardiovascular disease risk factor intervention among diabetic patients in Engl and was examined using data from the Health Surveys for Engl and 1991 - 94 . This evaluation included calculating the proportion who require  lipid lowering therapy  according to the St and ing Medical Advisory Committee ( SMAC ) guidelines . METHODS The Health Survey for Engl and is an annual , nationwide household-based in which anthropomorphic data , blood pressure , lipids and details of cardiovascular risk factors are collected from households after r and om stratification for geographical and socio-economic factors within a population sample of 39639 adults , 970 ( 2.3 % ) diabetic subjects were identified . RESULTS Overall , 51 % of those with diabetes had hypertension  ( systolic blood pressure > or = 160 mmHg or a diastolic BP > or = 95 mmHg or being on antihypertensive therapy ) , 27 % were  obese  ( body mass index > or = 30 kg/m2 ) and 19 % were current smokers . One-third of those with hypertension were untreated and less than one-half of those on treatment had their hypertension controlled to below 160/ 95 mmHg . More than one-quarter had poor glycaemic control ( glycated Hb>11 % or an HbA1c>7.5 % ) . Of those aged < 70 years , 29 % required  lipid lowering therapy  according to the SMAC guidelines and almost all ( 94 % ) of these were not on treatment . An analysis showed that , because the SMAC guidelines do not require high density lipoprotein ( HDL ) cholesterol to be measured , their use is likely to result in substantial underestimation of the need for  lipid lowering  , particularly in diabetic women . CONCLUSION In Engl and , among those with diabetes there is considerable unmet need for cardiovascular risk factor intervention , particularly for hypertension and raised cholesterol . With this baseline established , future improvements can be monitored BACKGROUND Cardiovascular disease is the main cause of morbidity and mortality in patients with type 2 diabetes mellitus ( DM ) . Intervention on  cardiovascular risk factors  ( CVRF ) is essential to obtain clinical results reducing the excess of cardiovascular risk ( CVR ) in these patients . METHODS The objective of this study was to describe the association of type 2 DM with modifiable cardiovascular risk factors and the degree of control of these in a population of type 2 diabetics in attendance in primary care clinics , and also to establish prospect ively whether an integral and multifactorial intervention on uncontrolled cardiovascular risk factors , carried out in conditions of routine clinical practice by applying an open protocol , could significantly reduce the estimated CVR according to the Framingham scale . The proposed intervention included both actions aim ed at modifying habits , and pharmacologic intervention to achieve an optimum level of control in accordance with international recommendations for the objectives and treatment for type 2 diabetes . RESULTS A total of 3466 patients with a mean age of 58 + /- 7.5 years were studied and followed-up for 1 year . Of these , 90.4 % of patients had high blood pressure ; 60.1 % of men and 32.7 % of women presented CVR > 20 % in 10 years according to the Framingham scale by categories . Intervention at 1 year of follow-up had achieved statistically significant reductions in blood pressure , glycated hemoglobin , and lipid levels , but not of patients ' body weight . After 1 year of follow-up , 29 % of males and 24 % of women with a high CVR ( > 20 % ) at the start of the study presented reduced risk levels . CONCLUSION The results of the study demonstrate that an integrated and multifactorial intervention in type 2 diabetic patients can achieve clinical ly significant reductions in CVR . However , conducted in effective conditions , it is not able to achieve optimum levels of control in spite of the initial proposal , possibly due to some degree of inertia in routine clinical practice BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest The Systolic Hypertension in Europe ( Syst-Eur ) study investigated whether antihypertensive treatment could decrease the risk of cardiovascular complications in elderly patients with isolated systolic hypertension . Patients > or = 60 years were r and omly assigned to treatment with the dihydropyridine calcium antagonist nitrendipine ( n = 2,398 ) , with the addition of enalapril and hydrochlorothiazide if needed , or to matching placebo  ( n = 2,297 ) . In the intent-to-treat analysis , the between-group difference in blood pressure was 10.1/4.5 mm Hg ( p < 0.001 ) . Active treatment decreased the total incidence of stroke ( the primary endpoint ) by 42 % ( p = 0.003 ) , of all cardiac endpoints by 26 % ( p = 0.03 ) , and of all cardiovascular endpoints combined by 31 % ( p < 0.001 ) . Cardiovascular mortality was somewhat lower with active treatment ( -27 % , p = 0.07 ) ; all-cause mortality was not significantly different ( -14 % ; p = 0.22 ) . For total ( p = 0.009 ) and cardiovascular ( p = 0.09 ) mortality , the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with lower systolic blood pressure at entry ( p = 0.05 ) . The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry . Antihypertensive therapy was at least as effective in patients with diabetes as in those without diabetes at entry . Further analyses suggested benefit in patients who were taking nitrendipine as monotherapy . Per- protocol analysis largely confirmed the intent-to-treat results . Active treatment decreased all strokes by 44 % ( p = 0.004 ) , all cardiac endpoints by 26 % ( p = 0.05 ) , and all cardiovascular endpoints by 32 % ( p < 0.001 ) . Total mortality was decreased by 26 % ( p = 0.05 ) , but the similar reduction in cardiovascular mortality did not reach significance in this analysis . It is concluded that stepwise antihypertensive drug treatment starting with nitrendipine improves prognosis in elderly patients with isolated systolic hypertension Atrial  fibrillation ( AF )  is prevalent in patients with type 2 diabetes mellitus ( DM ) and is associated with markers of poor glycemic control ; however , the impact of glycemic control on incident AF and outcomes is unknown . The aims of this study were to prospect ively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF . A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) cohort were studied in a r and omized , double-blind fashion . Participants were r and omized to an intensive therapeutic strategy targeting a glycated hemoglobin level of < 6.0 % or a st and ard strategy targeting a glycated hemoglobin level of 7.0 % to 7.9 % . Incident AF occurred in 159 patients ( 1.58 % ) over the follow-up period , at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the st and ard-therapy group ( p = 0.52 ) . In a multivariate model , predictors of incident AF were age , weight , diastolic blood pressure , heart rate , and heart failure history .  Patients with DM and new-onset AF  had a hazard ratio of 2.65 for all-cause mortality ( 95 % confidence interval 1.8 to 3.86 , p < 0.0001 ) , a hazard ratio of 2.1 for myocardial infa rct ion ( 95 % confidence interval 1.33 to 3.31 , p = 0.0015 ) , and a hazard ratio of 3.80 for the development of heart failure ( 95 % confidence interval 2.48 to 5.84 , p < 0.0001 ) . In conclusion , intensive glycemic control did not affect the rate of new-onset AF .  Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society The BBB study ( Swedish for Beh and la Blodtryck Bättre or Treat Blood Pressure Better ) was a multicenter trial design ed to investigate three aspects of antihypertensive treatment : i ) Is it possible to lower the diastolic blood pressure further in " well-treated " hypertensive patients through intensified therapy ? ii ) Can this aim be fulfilled without increasing the incidence or severity of side-effects ? iii ) If i ) and ii ) can be answered in the affirmative , will the further reduction in diastolic blood pressure be associated with a further reduction in hypertension-associated mortality and morbidity ? Altogether 2127 hypertensive men and women with an average age of 59.8 years ( 46 - 71 ) were recruited at 142 primary health care centers in Sweden . Approximately 10,000 patient-years were accumulated . All patients had treated essential hypertension and all had diastolic blood pressures in the range 90 - 100 mmHg on three consecutive visits before entering the study . The patients were r and omized to either intensified treatment aim ing at a blood pressure < or = 80 mmHg diastolic ( group A ) or to unchanged therapy ( group B ) . A difference between group A and group B in diastolic blood pressure of 7 - 7.5 mmHg was achieved for > 4 years . Adverse effects were studied in detail in 100 r and omly selected patients from each group using a special question naire and a visual analogue scale . The adverse effect score fell significantly in group A but remained unchanged in group B. Regarding cardiovascular morbidity and mortality there were no significant differences between groups A and B , the total number of strokes and myocardial infa rcts being 28 in group A and 29 in group B. ( ABSTRACT TRUNCATED AT 250 WORDS AIMS To examine whether  socioeconomic position ( SEP ) was associated with change in cardiovascular risk factors and meeting treatment targets for cardiovascular risk factors among individuals with screen-detected Type 2 DM at six-year follow-up . METHODS The study population was 1533 people with Type 2 DM identified from at stepwise diabetes screening programme in general practice during 2001 - 2006 in the ADDITION-Denmark study . The ADDITION- study was performed as a r and omised trial but the two r and omisation groups were analysed as one cohort in this study . Cardiovascular risk factors were measured at baseline and repeated at follow-up ( mean : 5.9 [ 1.4 ] years ) . Information on SEP , redeemed antihypertensive and lipid-lowering treatment  were obtained from Danish registers . Multivariate analyses were performed to estimate change in cardiovascular risk factors and difference in meeting treatment targets . RESULTS The change in HbA1c , cholesterol , blood pressure and BMI were virtually the same across educational level , income level , occupational status or cohabiting status . Overall , the ability to meet treatment targets for HbA1c , cholesterol and blood pressure was not modified by SEP-group . A higher proportion of people with lower educational level or lower income level in the intensive care redeemed anti-hypertensive treatment compared to people with higher educational or income levels . CONCLUSION Screen-detection and early treatment onset did not introduce socioeconomic ine quality in metabolic control in people with screen-detected Type 2 DM at six-year follow-up BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure OBJECTIVE The aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 ( insulin-dependent ) diabetic patients with kidney disease . DESIGN The study was a controlled , prospect i ve , parallel , 10-year follow-up trial . PATIENTS AND INTERVENTIONS A sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospect ively followed for 10 years . Forty-five patients ( intensified antihypertensive therapy ; IT group ) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians , consultants and local hospitals ( routine antihypertensive therapy ; RT group ) . OUTCOME MEASURES The main endpoint was death ; secondary endpoints were renal replacement therapy , blindness and amputation . RESULTS Blood pressure was reduced in the IT group and increased in the RT group . During the follow-up period , 29 patients died , seven in the IT group and 22 in the RT group . The survival curves were significantly different ( P = 0.0008 ) . The main causes of death were cardiac . In a multiple Cox proportional hazards model , allocation to the IT group reduced the mortality risk [ relative risk ( RR ) = 0.213 ; 95 % confidence interval 0.089 - 0.509 , P = 0.00051 , while age ( P = 0.0039 ) and mean blood pressure ( P= 0.0113 ) increased this risk . In multiple Cox or multiple logistic regression models , the risks of dialysis ( RR = 0.269 , 95 % confidence interval 0.110 - 0.656 , P = 0.0039 ) , blindness ( odds ratio = 0.158 , 95 % confidence interval 0.037 - 0.684 , P= 0.0136 ) , and amputation ( RR = 0.181 , 95 % confidence interval 0.047 - 0.703 , P= 0.0135 ) were significantly lower in the IT group compared with the RT group ( log rank P = 0.0008 ) . CONCLUSION We conclude that intensified antihypertensive treatment , based on a hypertension teaching and treatment programme , reduces long-term morbidity and mortality in patients with diabetic nephropathy The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter trial being conducted in 26 countries . Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure ( < or = 90 , < or = 85 or < or = 80 mmHg ) and cardiovascular morbidity and mortality in hypertensive patients . In addition , the study will examine the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) or placebo . In the HOT Study , basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily . If target blood pressure is not reached , additional antihypertensive therapy with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent is given . Further dosage adjustments are made in accordance with a set protocol . As a fifth and final step , a diuretic may be added . Inclusion of patients was stopped on April 30 , 1994 . At that time 19,196 patients had been r and omized . There were 9,055 ( 47 % ) women and 10,141 ( 53 % ) men with an average age of 61.5 + /- 7.5 ( SD ) years . At enrollment , 52 % of patients were receiving antihypertensive treatment . These patients entered a wash-out period of at least 2 weeks before r and omization . The average r and omization blood pressure in untreated patients was 169 + /- 14/106 + /- 3 mmHg and in the treated patients 170 + /- 14/105 + /- 3 mmHg . On August 15 , 1994 , blood pressure data were available for 14,710 and 10,275 patients , who had completed 3 and 6 months treatment , respectively . The average reduction in diastolic blood pressure was 22 mmHg after 6 months . ( ABSTRACT TRUNCATED AT 250 WORDS Background — In rural areas in China and India , the cardiovascular disease burden is high but economic and healthcare re sources are limited . This study ( the Simplified Cardiovascular Management Study [ SimCard ] ) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system . Methods and Results — The SimCard study was a yearlong cluster-r and omized , controlled trial conducted in 47 villages ( 27 in China and 20 in India ) . Recruited for the study were 2086 individuals with high cardiovascular risk ( aged ≥40 years with self-reported history of coronary heart disease , stroke , diabetes mellitus , and /or measured systolic blood pressure ≥160 mm Hg ) . Participants in the intervention villages were managed by community health workers through an And roid-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications . In comparison with the control group , the intervention group had a 25.5 % ( P<0.001 ) higher net increase in the primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention . There were also significant differences in certain secondary outcomes : aspirin use ( net difference : 17.1 % ; P<0.001 ) and systolic blood pressure ( –2.7 mm Hg ; P=0.04 ) . However , no significant changes were observed in the lifestyle factors . The intervention was culturally tailored , and country-specific results revealed important differences between the regions . Conclusions — The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in re source -poor setting s in China and India . Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01503814 BACKGROUND Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension . We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events . In this post hoc analysis , we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients . METHODS After stratification according to center , sex , and presence or absence of previous cardiovascular complications , 4695 patients ( age , > or = 60 years ) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were r and omly assigned to receive active treatment or placebo . Active treatment consisted of nitrendipine ( 10 to 40 mg per day ) with the possible addition or substitution of enalapril ( 5 to 20 mg per day ) or hydrochlorothiazide ( 12.5 to 25 mg per day ) or both , titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg . In the control group , matching placebo tablets were administered similarly . RESULTS At r and omization , 492 patients ( 10.5 percent ) had diabetes . After a median follow-up of two years , the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg , respectively , among the diabetic patients . Among the 4203 patients without diabetes , systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg , respectively , in the two groups . After adjustment for possible confounders , active treatment was found to have reduced overall mortality by 55 percent ( from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients ) , mortality from cardiovascular disease by 76 percent , all cardiovascular events combined by 69 percent , fatal and nonfatal strokes by 73 percent , and all cardiac events combined by 63 percent in the group of patients with diabetes . Among the nondiabetic patients , active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent . In the group of patients receiving active treatment , reductions in overall mortality , mortality from cardiovascular disease , and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients ( P=0.04 , P=0.02 , and P=0.01 , respectively ) . CONCLUSIONS Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension . Thus , our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events ( OPERA ) trial is a large clinical trial of omapatrilat , a vasopeptidase inhibitor , in patients with stage 1 isolated systolic hypertension ( ISH ) . OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition . This 5-year multinational , r and omized , double-blind , parallel-group , placebo-controlled , forced-titration study will be conducted in approximately 12,600 subjects r and omized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years . The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat ( target dose 40 mg ) will reduce cardiovascular ( CV ) morbidity and mortality in older ( > or = 65 years ) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence -based requirement for treatment .  Blood pressure inclusion criteria are  systolic blood pressure ( SBP ) 140 to 159 mm Hg ( SBP 125 to 139 mm Hg in diabetic individuals ) and diastolic blood pressure ( DBP ) < 90 mm Hg . The primary end point is defined as the composite of fatal/nonfatal stroke , fatal/nonfatal myocardial infa rct ion , fatal/nonfatal heart failure , and other CV mortality . Secondary end points include the individual components of the primary end point , CV mortality , and major cardiovascular end points , as well as effects on cognitive function and initiation of treatment for diabetes . Additional analyses will be conducted in men and women , in diabetic patients , in different risk classes and according to prior evidence of vascular disease The overall quality of antihypertensive care in diabetic patients in Germany is poor . Only a minority of unselected hypertensive patients reach permanent normotensive blood pressure control . Previously , we have shown in a prospect i ve r and omized 3-year follow-up study in essential hypertension that implementation of a hypertension teaching and treatment program into routine care results in a significant improvement of blood pressure control . Subsequently , we have performed a prospect i ve , controlled 5-year follow-up trial in hypertensive type I diabetic patients with nephropathy . One-half of a sequential sample of about 100 hypertensive patients with overt nephropathy participated in the program based on blood pressure self-monitoring with the goal of normalization of blood pressure values below 140/90 mm Hg ( intensified care , IC ) . The remaining patients followed routine antihypertensive therapy and formed the control group ( routine care , RC ) . During 5 years of follow-up in IC group patients , blood pressure control was significantly improved . The occurrence of primary study end points ( need for dialysis and death ) was significantly lower in the IC group patients . In conclusion , in patients with diabetic nephropathy , participation in a hypertension teaching treatment program results in a long-term improvement of blood pressure control and a decrease in mortality and morbidity The aim of this study was to evaluate the association between dementia and common vascular risk factors including blood pressure , blood lipids , homocysteine and diabetes mellitus in a population of very old people . This study is a 9-year follow-up prospect i ve population -based study monitoring 339 non-demented subjects aged 85 years or over in the city of Vantaa , Southern Finl and . During the follow-up , those individuals with diabetes mellitus at the baseline and new incident stroke had a higher probability for developing dementia . History of hypertension or higher level of education were associated with a lower probability of dementia . It seems that the contribution of vascular risk factors to the risk of dementia may be age-dependent and their role in the very old subjects may be mediated through their influence on cerebrovascular morbidity . Thus , prevention of stroke and diabetes mellitus may reduce the risk of cognitive decline in the very old The European Working Party on High blood pressure in the Elderly ( EWPHE ) trial was a double-blind r and omized placebo-controlled trial of antihypertensive treatment in patients over the age of 60 years . Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range of 90 - 119 mmHg and a systolic blood pressure in the range of 160 - 239 mmHg . Eight-hundred and forty patients were r and omly assigned either to active treatment ( hydrochlorothiazide + triamterene ) or a matching placebo . If blood pressure remained elevated methyldopa was added to the active regimen and matching placebo to the placebo regimen . Before r and omization , the patients were stratified in eight strata according to sex , age groups between 60 and 69 years or 70 years and over , and the presence or absence of cardiovascular complications of hypertension . Both the intention-to-treat and ' on r and omized treatment ' analyses suggested a benefit from active treatment in men and women . Formal statistical significance was achieved for male cardiovascular mortality ( intention-to-treat analyses ) and for cardiovascular events in females . Although the event rates were greater for patients with previous cardiovascular events and patients over the age of 70 years , the percentage reduction in cardiovascular events was similar in these groups to those without complications and in patients between 60 and 69 years of age . However , little benefit from treatment could be demonstrated in patients over the age of 80 years . The presence or absence of smoking had no influence on response to treatment in these elderly patients 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 We design ed this study to explore to what extent the excess risk of cardiovascular events in diabetic individuals is attributable to hypertension . We retrospectively analyzed prospect ively collected data from the Framingham original and offspring cohorts . Of the 1145 Framingham subjects newly diagnosed with diabetes mellitus who did not have a previous history of cardiovascular events , 663 ( 58 % ) had hypertension at the time that diabetes mellitus was diagnosed . During 4154 person-years of follow-up , 125 died , and 204 experienced a cardiovascular event .  Framingham participants with hypertension at the time of diabetes mellitus diagnosis exhibited higher rates of all-cause mortality ( 32 versus 20 per 1000 person-years ; P<0.001 ) and cardiovascular events ( 52 versus 31 per 1000 person-years ; P<0.001 ) compared with normotensive subjects with diabetes mellitus . After adjustment for demographic and clinical covariates , hypertension was associated with a 72 % increase in the risk of all-cause death and a 57 % increase in the risk of any cardiovascular event in individuals with diabetes mellitus . The population -attributable risk from hypertension in individuals with diabetes mellitus was 30 % for all-cause death and 25 % for any cardiovascular event ( increasing to 44 % and 41 % , respectively , if the 110 normotensive subjects who developed hypertension during follow-up were excluded from the analysis ) . In comparison , after adjustment for concurrent hypertension , the population -attributable risk from diabetes mellitus in Framingham subjects was 7 % for all-cause mortality and 9 % for any cardiovascular disease event . Although diabetes mellitus is associated with increased risks of death and cardiovascular events in Framingham subjects , much of this excess risk is attributable to coexistent hypertension Diabetes mellitus contributes substantially to the global burden of disease , with an estimated 100 million people affected worldwide , and its prevalence is increasing rapidly.1 Macrovascular complications are among the chief causes of major morbidity in people with diabetes , and most of their deaths are attributed to cardiovascular causes.2 3 In type 2 ( “ non-insulin dependent ” ) diabetes , blood triglyceride concentrations tend to be raised and high density lipoprotein ( HDL ) cholesterol concentrations reduced even with good metabolic control , whereas a similar pattern tends to emerge in type 1 ( “ insulin dependent ” ) diabetes mellitus only when glycaemic control is poor.4 5 Typically in both type 1 and type 2 diabetes , however , blood concentrations of total and low density lipoprotein ( LDL ) cholesterol are similar to those in the general population . This may have contributed to the belief that LDL cholesterol is of little relevance to the risk of cardiovascular disease in diabetes4 6 and , apart from those with pronounced dyslipidaemia or pre-existing coronary heart disease ( CHD ) , most people with diabetes do not receive cholesterol lowering treatment despite their increased risk . Prospect i ve epidemiological studies in the general population show that there is a positive association between CHD risk and blood total cholesterol concentration , which continues down at least to 3 mmol/l ( that is , well below the range commonly seen in western population s)7 without any evidence of a “ threshold ” below which lower cholesterol is not associated with lower risk . In these observational studies , the continuous association is roughly linear between CHD risk plotted on a doubling scale and the concentration of total or LDL cholesterol . This implies that the proportional reduction in CHD risk associated with a particular prolonged absolute difference in cholesterol is similar throughout the range studied . Hence , the absolute size of the reduction in CHD produced by lowering LDL cholesterol by BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease . Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes , but similar data are not available for patients with type 2 , the most common form of diabetes . We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy . METHODS A total of 1513 patients were enrolled in this r and omized , double-blind study comparing losartan ( 50 to 100 mg once daily ) with placebo , both taken in addition to conventional antihypertensive treatment ( calcium-channel antagonists , diuretics , alpha-blockers , beta-blockers , and central ly acting agents ) , for a mean of 3.4 years . The primary outcome was the composite of a doubling of the base-line serum creatinine concentration , end-stage renal disease , or death . Secondary end points included a composite of morbidity and mortality from cardiovascular causes , proteinuria , and the rate of progression of renal disease . RESULTS A total of 327 patients in the losartan group reached the primary end point , as compared with 359 in the placebo group ( risk reduction , 16 percent ; P=0.02 ) . Losartan reduced the incidence of a doubling of the serum creatinine concentration ( risk reduction , 25 percent ; P=0.006 ) and end-stage renal disease ( risk reduction , 28 percent ; P=0.002 ) but had no effect on the rate of death . The benefit exceeded that attributable to changes in blood pressure . The composite of morbidity and mortality from cardiovascular causes was similar in the two groups , although the rate of first hospitalization for heart failure was significantly lower with losartan ( risk reduction , 32 percent ; P=0.005 ) . The level of proteinuria declined by 35 percent with losartan ( P<0.001 for the comparison with placebo ) . CONCLUSIONS Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy , and it was generally well tolerated The C and esartan Antihypertensive Survival Evaluation in Japan Trial was design ed to compare the long-term effects of the angiotensin II receptor blocker c and esartan and the calcium channel blocker amlodipine on the incidence of cardiovascular events , represented as a composite of sudden death and cerebrovascular , cardiac , renal , and vascular events in high-risk Japanese hypertensive patients . We conducted a prospect i ve , r and omized , open-label study with blinded assessment of the end point in 4728 Japanese hypertensive patients ( mean age : 63.8 years ; mean body mass index : 24.6 kg/m2 ) . Patients were followed for an average of 3.2 years .  Blood pressure was well controlled with both treatment-based regimens ( systolic blood pressure/diastolic blood pressure : 136.1/77.3 mm Hg for c and esartan-based regimens and 134.4/76.7 mm Hg for amlodipine-based regimens after 3 years ) . Primary cardiovascular events occurred in 134 patients with both the c and esartan- and amlodipine-based regimens . The 2 treatment-based regimens produced no significant differences in cardiovascular morbidity or mortality in the high-risk Japanese hypertensive patients ( hazard ratio : 1.01 ; 95 % CI : 0.79 to 1.28 ; P=0.969 ) . In each primary end point category , there was no significant difference between the 2 treatment-based regimens . New-onset diabetes occurred in fewer patients taking c and esartan ( 8.7/1000 person-years ) than in those taking amlodipine ( 13.6/1000 person-years ) , which result ed in a 36 % relative risk reduction ( hazard ratio : 0.64 ; 95 % CI : 0.43 to 0.97 ; P=0.033 ) . We disclosed that c and esartan-based and amlodipine-based regimens produced no statistical differences in terms of the primary cardiovascular end point , whereas c and esartan prevented new-onset diabetes more effectively than amlodipine 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 Background Arterial stiffness is increased in patients with CKD and is a powerful predictor of cardiovascular morbidity and mortality . Use of the xanthine oxidase inhibitor allopurinol has been shown to improve endothelial function , reduce left ventricular hypertrophy and possibly improve cardiovascular outcome . We explored the relationship between use of allopurinol and arterial stiffness in patients with chronic kidney disease ( CKD ) . Methods Cross-sectional observational study of 422 patients with CKD with evidence of , or at high risk of , renal disease progression . Arterial stiffness was determined by carotid-femoral pulse wave velocity ( PWV ) . Results The mean age was 63±16 years , median estimated glomerular filtration rate was 25 ( interquartile range : 19–31 ) ml/min/1.73 m2 and mean PWV was 10.2±2.4 m/s . Seventy-seven patients ( 18 % ) were receiving regular allopurinol , 61 % at a dose of 100 mg/day ( range : 50–400 mg/day ) . Patients receiving allopurinol had significantly lower peripheral pulse pressure , central pulse pressure , central systolic blood pressure , serum uric acid level tissue advanced glycation end product levels but comparable high-sensitivity C-reactive protein levels . Use of allopurinol was associated with lower PWV . After adjusting for age , gender , ethnicity , tissue advanced glycation end product level , peripheral pulse pressure , smoking pack years , presence of diabetes mellitus and use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker , the use of allopurinol remained a significant independent determinant of PWV ( mean difference : −0.63 m/s ; 95 % CI , −0.09 to −1.17 m/s , p = 0.02 ) . Conclusion In patients with CKD , use of allopurinol is independently associated with lower arterial stiffness . This study provides further justification for a large definitive r and omised controlled trial examining the therapeutic potential of allopurinol to reduce cardiovascular risk in people with CKD Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk . The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study .  Urinary albumin/creatinine ratio ( UACR ) was measured at baseline and annually . Time-varying albuminuria was closely related to risk for the primary composite end point ( ie , when UACR decreased during treatment , risk was reduced accordingly ) . When the population was divided according to median baseline value ( 1.21 mg/mmol ) and median year 1 UACR ( 0.67 mg/mmol ) , risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 ( 5.5 % ) , to low baseline/high year 1 ( 8.6 % ) , to high baseline/low year 1 ( 9.4 % ) , and to high baseline/high year 1 ( 13.5 % ) values . Similar significant , stepwise increases in risk were seen for the components of the primary composite end point ( cardiovascular mortality , stroke , and myocardial infa rct ion ) . The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure . We propose that monitoring of albuminuria should be an integrated part of the management of hypertension . If albuminuria is not decreased by the patient ’s current antihypertensive and other treatment , further intervention directed toward blood pressure control and other modifiable risks should be considered Objectives To investigate the performance of classic risk factors , and of some new biomarkers , in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease . Design The Leiden 85-plus Study ( 1997 - 2004 ) is an observational prospect i ve cohort study with 5 years of follow-up . Setting General population of the city of Leiden , the Netherl and s. Participants Population based sample of participants aged 85 years ( 215 women and 87 men ) with no history of cardiovascular disease ; no other exclusion criteria . Main measurements Cause specific mortality was registered during follow-up . All classic risk factors included in the Framingham risk score ( sex , systolic blood pressure , total and high density lipoprotein cholesterol , diabetes mellitus , smoking and electrocardiogram based left ventricular hypertrophy ) , as well as plasma concentrations of the new biomarkers homocysteine , folic acid , C reactive protein , and interleukin 6 , were assessed at baseline . Results During follow-up , 108 of the 302 participants  died ; 32 % ( 35/108 ) of deaths were from cardiovascular causes . Classic risk factors did not predict cardiovascular mortality when used in the Framingham risk score ( area under receiver operating characteristic curve 0.53 , 95 % confidence interval 0.42 to 0.63 ) or in a newly calibrated model ( 0.53 , 0.43 to 0.64 ) . Of the new biomarkers studied , homocysteine had most predictive power ( 0.65 , 0.55 to 0.75 ) . Entering any additional risk factor or combination of factors into the homocysteine prediction model did not increase its discriminative power . Conclusions In very old people from the general population with no history of cardiovascular disease , concentrations of homocysteine alone can accurately identify those at high risk of cardiovascular mortality , whereas classic risk factors included in the Framingham risk score do not . These preliminary findings warrant validation in a separate cohort BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure  , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy OBJECTIVE To assess the effect of low-dose , diuretic-based antihypertensive treatment on major cardiovascular disease ( CVD ) event rates in older , non-insulin-treated diabetic patients with isolated systolic hypertension ( ISH ) , compared with nondiabetic patients . DESIGN Double-blind , r and omized , placebo-controlled trial : the Systolic Hypertension in the Elderly Program ( SHEP ) . SETTING Multiple clinical and support centers in the United States . PARTICIPANTS A total of 4736 men and women aged 60 years and older at baseline with ISH ( systolic blood pressure [ BP ] , > or = 160 mm Hg ; diastolic BP , < 90 mm Hg ) at baseline , 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients ( 4 additional patients not so classifiable were r and omized but not included in these analyses ) . Diabetes mellitus defined as physician diagnosis , taking oral hypoglycemic drugs , fasting glucose level of 7.8 mmol/L or more ( > or = 140 mg/dL ) , or any combination of these characteristics . INTERVENTION The active treatment group received a low dose of chlorthalidone ( 12.5 - 25.0 mg/d ) with a step-up to atenolol ( 25.0 - 50.0 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed . The placebo group received placebo and any active antihypertensive drugs prescribed by patient 's private physician for persistently high BP . MAIN OUTCOME MEASURES The 5-year rates of major CVD events , nonfatal plus fatal stroke , nonfatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) , major CHD events , and all-cause mortality . RESULTS The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients , with few adverse effects . For both diabetic and nondiabetic patients , all outcome rates were lower for participants r and omized to the active treatment group than for those r and omized to the placebo group . Thus , 5-year major CVD rate was lower by 34 % for active treatment compared with placebo , both for diabetic patients ( 95 % confidence interval [ CI ] , 6%-54 % ) and nondiabetic patients ( 95 % CI , 21%-45 % ) . Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients ( 101/1000 vs 51/1000 r and omized participants at the 5-year follow-up ) , reflecting the higher risk of diabetic patients . CONCLUSION Low-dose diuretic-based ( chlorthalidone ) treatment is effective in preventing major CVD events , cerebral and cardiac , in both non-insulin-treated diabetic and nondiabetic older patients with ISH Summary The latter was due to a reduction in cardiac mortality ( −38 % , p=0.036 ) and a nonsignificant decrease in cerebrovascular mortality ( −32 % , p=0.16 ) . In the double-blind part of the trial , the total mortality rate was not significantly reduced ( −26 % , p=0.077 ) . However , cardiovascular mortality was reduced in the actively treated group ( −38 % , p=0.023 ) , owing to a reduction in cardiac deaths ( −47 % , p=0.048 ) and a non-significant decrease in cerebrovascular mortality ( −43 % , p=0.15 ) . Deaths from myocardial infa rct ion were reduced ( −60 % , p=0.043 ) , and study -terminating morbid cardiovascular events were significantly reduced by active treatment ( −60 % , p=0.0064 ) . Non-terminating cerebrovascular events were reduced ( −52 % , p=0.026 ) , but the non-terminating cardiac events were not ( + 3 % , p=0.98 ) . In the patients r and omised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial . A double-blind r and omised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60 . Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90 to 119 mm Hg and a systolic pressure in the range 160 to 239 mm Eg . 840 patients were r and omised either to active treatment ( hydrochlorothiazide and triamterene ) or to  matching placebo  . If the blood pressure remained raised , methyldopa was added to the active regimen and matching placebo in the placebo group . An overall intention-to-treat analysis , combining the double-blind part of the trial and all subsequent follow-up , revealed a non-significant change in total mortality rate ( −9 % , p=0.41 ) but a significant reduction in cardiovascular mortality rate ( −27 % , p=0.037 ) BACKGROUND Intensive treatment ( IT ) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain . OBJECTIVE To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes . DESIGN Pragmatic , multicentre , cluster-r and omised , parallel-group trial . SETTING Three hundred and forty-three general practice s in Denmark , the Netherl and s , and Cambridge and Leicester , UK . PARTICIPANTS Individuals aged 40 - 69 years with screen-detected diabetes . INTERVENTIONS Screening plus routine care ( RC ) according to national guidelines or IT comprising screening and promotion of target-driven intensive management ( medication and promotion of healthy lifestyles ) of hyperglycaemia , blood pressure and cholesterol . MAIN OUTCOME MEASURES The primary end point was a composite of first cardiovascular event ( cardiovascular mortality/morbidity , revascularisation and non-traumatic amputation ) during a mean [ st and ard deviation ( SD ) ] follow-up of 5.3 ( 1.6 ) years . Secondary end points were ( 1 ) all-cause mortality ; ( 2 ) microvascular outcomes ( kidney function , retinopathy and peripheral neuropathy ) ; and ( 3 ) patient-reported outcomes ( health status , well-being , quality of life , treatment satisfaction ) . Economic analyses estimated mean costs ( UK 2009/10 prices ) and quality -adjusted life-years from an NHS perspective . We extrapolated data to 30 years using the UK Prospect i ve Diabetes Study outcomes model [ version 1.3 ; ( © ) Isis Innovation Ltd 2010 ; see www.dtu.ox.ac.uk/ outcomes model ( accessed 27 January 2016 ) ] . RESULTS We included 3055 ( RC , n = 1377 ; IT , n = 1678 ) of the 3057 recruited patients [ mean ( SD ) age 60.3 ( 6.9 ) years ] in intention-to-treat analyses . Prescription of glucose-lowering , antihypertensive and lipid-lowering medication increased in both groups , more so in the IT group than in the RC group . There were clinical ly important improvements in cardiovascular risk factors in both study groups . Modest but statistically significant differences between groups in reduction in glycated haemoglobin ( HbA1c ) levels , blood pressure and cholesterol favoured the IT group . The incidence of first cardiovascular event [ IT 7.2 % , 13.5 per 1000 person-years ; RC 8.5 % , 15.9 per 1000 person-years ; hazard ratio 0.83 , 95 % confidence interval ( CI ) 0.65 to 1.05 ] and all-cause mortality ( IT 6.2 % , 11.6 per 1000 person-years ; RC 6.7 % , 12.5 per 1000 person-years ; hazard ratio 0.91 , 95 % CI 0.69 to 1.21 ) did not differ between groups . At 5 years , albuminuria was present in 22.7 % and 24.4 % of participants in the IT and RC groups , respectively [ odds ratio ( OR ) 0.87 , 95 % CI 0.72 to 1.07 ) , retinopathy in 10.2 % and 12.1 % , respectively ( OR 0.84 , 95 % CI 0.64 to 1.10 ) , and neuropathy in 4.9 % and 5.9 % ( OR 0.95 , 95 % CI 0.68 to 1.34 ) , respectively . The estimated glomerular filtration rate increased between baseline and follow-up in both groups ( IT 4.31 ml/minute ; RC 6.44 ml/minute ) . Health status , well-being , diabetes-specific quality of life and treatment satisfaction did not differ between the groups . The intervention cost £ 981 per patient and was not cost-effective at costs ≥ £ 631 per patient . CONCLUSIONS Compared with RC , IT was associated with modest increases in prescribed treatment , reduced levels of risk factors and non-significant reductions in cardiovascular events , microvascular complications and death over 5 years . IT did not adversely affect patient-reported outcomes . IT was not cost-effective but might be if delivered at a reduced cost . The lower than expected event rate , heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups . Further follow-up to assess the legacy effects of early IT is warranted . TRIAL REGISTRATION Clinical Trials.gov NCT00237549 . FUNDING DETAILS This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 64 . See the NIHR Journals Library website for further project information INTRODUCTION Diabetic nephropathy is the leading cause of end-stage renal disease . Interruption of the renin-angiotensin system slows the progression of renal disease in type 1 diabetic patients , but similar data are not available for type 2 , the most common form of diabetes . We assessed the role of the angiotensin II receptor antagonist , losartan , in type 2 diabetic patients with nephropathy . MATERIAL AND METHODS One thous and five hundred and thirteen patients were enrolled in this r and omised , placebo-controlled study of  losartan ( 50 to 100 mg , once daily ) or placebo , in addition to conventional antihypertensive treatment ( calcium antagonists , diuretics , alpha- and beta-blockers , central ly acting agents ) for a mean of 3.4 years . The primary outcome was the composite of doubling of baseline serum creatinine , end-stage renal disease , or death . Secondary end points included a composite of cardiovascular morbidity and mortality , proteinuria , and the progression rate of renal disease . RESULTS Baseline demographics in the two groups were similar . Three hundred and twenty-seven patients receiving losartan reached the primary end point , as compared with 359 on placebo ( risk reduction = 16 per cent , p = 0.02 ) . Losartan reduced the incidence of doubling of serum creatinine ( risk reduction = 25 per cent , p = 0.006 ) and end-stage renal disease ( risk reduction = 28 per cent , p = 0.002 ) , but had no effect on death . Benefits exceeded that attributable to changes in blood pressure . The composite of cardiovascular morbidity and mortality was similar in the two groups , except hospitalisation for heart failure , which was reduced with losartan ( risk reduction = 32 per cent , p = 0.005 ) . Proteinuria declined by 35 per cent with losartan ( p < 0.001 ) . DISCUSSION Losartan conferred significant renal benefits in type 2 diabetic patients with nephropathy and was generally well tolerated Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure .  To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 ) BACKGROUND There is no evidence from r and omized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus . We investigated whether therapy targeting normal systolic pressure ( i.e. , < 120 mm Hg ) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events . METHODS A total of 4733 participants with type 2 diabetes were r and omly assigned to intensive therapy , targeting a systolic pressure of less than 120 mm Hg , or st and ard therapy , targeting a systolic pressure of less than 140 mm Hg . The primary composite outcome was nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS After 1 year , the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the st and ard-therapy group . The annual rate of the primary outcome was 1.87 % in the intensive-therapy group and 2.09 % in the st and ard-therapy group ( hazard ratio with intensive therapy , 0.88 ; 95 % confidence interval [ CI ] , 0.73 to 1.06 ; P=0.20 ) . The annual rates of death from any cause were 1.28 % and 1.19 % in the two groups , respectively ( hazard ratio , 1.07 ; 95 % CI , 0.85 to 1.35 ; P=0.55 ) . The annual rates of stroke , a prespecified secondary outcome , were 0.32 % and 0.53 % in the two groups , respectively ( hazard ratio , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group ( 3.3 % ) and 30 of the 2371 participants in the st and ard-therapy group ( 1.3 % ) ( P<0.001 ) . CONCLUSIONS In patients with type 2 diabetes at high risk for cardiovascular events , targeting a systolic blood pressure of less than 120 mm Hg , as compared with less than 140 mm Hg , did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events . ( Clinical Trials.gov number , NCT00000620 . Diuretics and & bgr;-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials . No study has compared newer more costly antihypertensive agents ( calcium antagonists , ACE inhibitors , and & agr;-adrenergic blockers ) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients . The study is a r and omized , double-blind , active-controlled clinical trial design ed to determine whether the incidence of the primary outcome , fatal coronary heart disease or nonfatal myocardial infa rct ion , differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs . Men and women aged ≥55 years with at least 1 other cardiovascular disease risk factor were r and omly assigned to chlorthalidone ( 12.5 to 25 mg/d ) , amlodipine ( 2.5 to 10 mg/d ) , lisinopril ( 10 to 40 mg/d ) , or doxazosin ( 2 to 8 mg/d ) for planned follow-up of 4 to 8 years . This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) participants . A total of 42 448 participants were r and omized from 625 sites in the United States , Canada , Puerto Rico , and the US Virgin Isl and s. The mean age was 67 years , with 35 % aged ≥70 years . Among those r and omized , 36 % were black , 19 % were Hispanic , and 47 % were women . The sample includes a high proportion of people with diabetes ( 36 % ) , patients with existing cardiovascular disease ( 47 % ) , and smokers ( 22 % ) . There were no important differences between the r and omized treatment groups at baseline . ALLHAT will add greatly to our underst and ing of the management of hypertension by providing an answer to the following question : are newer antihypertensive agents similar , superior , or inferior to traditional treatment with diuretics OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 BACKGROUND Blood pressure shows an inverse association with mortality in patients with chronic kidney disease ( CKD ) on dialysis .  It is unclear if the same phenomenon exists in patients with CKD not yet on dialysis . METHODS We examined the association of  systolic ( SBP ) and diastolic ( DBP ) blood pressure  with  all-cause mortality  in a historical prospect i ve cohort of 860 patients ( age 68.1+/-10.1 years , 99.1 % male , 24.4 % black ) with estimated glomerular filtration rate ( GFR ) < 60 ml/min/1.73 m2 . We used Cox models to adjust for the effects of age , race , diabetes mellitus , atherosclerotic cardiovascular disease ( ASCVD ) , congestive heart failure , smoking , antihypertensive medications , body mass index , GFR , albumin , cholesterol , haemoglobin and proteinuria . To examine the role of comorbidities , we performed subgroup analyses based on prevalent ASCVD status and level of estimated GFR . RESULTS Higher SBP and higher DBP were both associated with lower mortality [ adjusted hazard ratio ( 95 % confidence interval ) for SBP 133 - 154 , 155 - 170 and > 170 mmHg , compared with < 133 mmHg , respectively : 0.61 ( 0.44 - 0.85 ) , 0.62 ( 0.45 - 0.87 ) and 0.68 ( 0.49 - 0.96 ) ; and for DBP 65 - 75 , 76 - 86 and > 86 mmHg , compared with < 65 mmHg : 0.85 ( 0.62 - 1.18 ) , 0.72 ( 0.52 - 1.00 ) and 0.60 ( 0.41 - 0.86 ) ] . The same association was present for both SBP and DBP only in subgroups with GFR < or = 30 ml/min/1.73 m2 and for DBP only in the subgroup with ASCVD . CONCLUSIONS Lower blood pressure is associated with higher mortality in patients with moderate to severe CKD , but interactions with kidney function and with ASCVD suggest that blood pressure may play a surrogate rather than a causative role in this association CONTEXT Impaired coronary circulatory function predicts cardiovascular events , the leading cause of death in patients with diabetes mellitus . Aldosterone causes cardiovascular injury and is not suppressed by chronic angiotensin converting enzyme ( ACE ) inhibitor therapy . OBJECTIVE Our objective was to assess whether mineralocorticoid receptor activation contributes to coronary circulatory dysfunction in patients with diabetes who are already receiving ACE inhibitor therapy . DESIGN AND SETTING A r and omized , double-blind , crossover study with an intervening washout period of at least 4 wk was conducted with ambulatory patients from the community . PATIENTS Patients included 16 subjects ( 11 men , eight Caucasians ; mean age , 53 yr ; mean body mass index , 38.0 kg/m2 ) with diabetes and albuminuria but without clinical cardiovascular disease . INTERVENTIONS ACE inhibitors were switched to enalapril 20 mg daily , and other antihypertensives were discontinued . Amlodipine 5 - 10 mg daily was added to achieve blood pressures less than 130/80 mm Hg . Subjects then received , in r and om order , 6 wk of the mineralocorticoid receptor antagonist eplerenone 50 mg ( with placebo pill ) daily and 6 wk of another diuretic , hydrochlorothiazide 12.5 mg ( with potassium 10 mEq ) daily . MAIN OUTCOME MEASURES Before and after each 6-wk treatment period , we measured coronary circulatory function ( adenosine-stimulated myocardial perfusion reserve ) and endothelial function ( brachial artery reactivity and peripheral arterial tonometry ) . RESULTS The eplerenone and hydrochlorothiazide groups had similar blood pressures , serum potassium , glycemia , and endothelial function . Although pretreatment myocardial perfusion reserve did not differ between groups , myocardial perfusion reserve was significantly higher after eplerenone than after hydrochlorothiazide ( median 1.57 vs. 1.30 ; P = 0.03 ) . CONCLUSIONS Mineralocorticoid receptor blockade improves coronary circulatory function compared with hydrochlorothiazide in patients with diabetes already receiving ACE inhibitor therapy BACKGROUND Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension . The significance of this finding is uncertain . Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic , calcium-channel blocker , or angiotensin-converting enzyme inhibitor on fasting glucose ( FG ) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus ( DM ) in 3 treatment groups . METHODS We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) among nondiabetic participants who were r and omized to receive treatment with chlorthalidone ( n = 8419 ) , amlodipine ( n = 4958 ) , or lisinopril ( n = 5034 ) and observed for a mean of 4.9 years . RESULTS Mean FG levels increased during follow-up in all treatment groups . At year 2 , those r and omized to the chlorthalidone group had the greatest increase ( + 8.5 mg/dL [ 0.47 mmol/L ] vs + 5.5 mg/dL [ 0.31 mmol/L ] for amlodipine and + 3.5 mg/dL [ 0.19 mmol/L ] for lisinopril ) . The odds ratios for developing DM with lisinopril ( 0.55 [ 95 % confidence interval , 0.43 - 0.70 ] ) or amlodipine ( 0.73 [ 95 % confidence interval , 0.58 - 0.91 ] ) vs chlorthalidone at 2 years were significantly lower than 1.0 ( P<.01 ) . There was no significant association of FG level change at 2 years with subsequent coronary heart disease , stroke , cardiovascular disease , total mortality , or end-stage renal disease . There was no significant association of incident DM at 2 years with clinical outcomes , except for coronary heart disease ( risk ratio , 1.64 ; P = .006 ) , but the risk ratio was lower and nonsignificant in the chlorthalidone group ( risk ratio , 1.46 ; P = .14 ) . CONCLUSIONS Fasting glucose levels increase in older adults with hypertension regardless of treatment type . For those taking chlorthalidone vs other medications , the risk of developing FG levels higher than 125 mg/dL ( 6.9 mmol/L ) is modestly greater , but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events Most patients with type 2 diabetes mellitus develop cardiovascular disease ( CVD ) , with substantial loss of life expectancy . Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes . The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge . Despite the importance of this health problem , there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial is a r and omized , multicenter , double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors . ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality . All participants are in the glycemia trial , which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin ( HbA1c ) level of < 6.0 % will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9 % . The lipid trial includes 5,518 of the participants , who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether , in the context of good glycemic control , a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo . The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of < 120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of < 140 mm Hg . The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event , specifically nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . Upon the expected completion of participant follow-up in 2009 , the ACCORD trial should document for the first time the benefits and risks of intensive glucose control , intensive blood pressure control , and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes AIMS Cardiovascular disease ( CVD ) is the leading cause of morbidity and mortality in people with diabetes in South Asia . The CARRS Translation Trial tests the effectiveness , cost-effectiveness , and sustainability of a clinic-based multi-component CVD risk reduction intervention among people with diabetes in India and Pakistan . METHODS We r and omly assigned 1146 adults with diabetes recruited from 10 urban clinic sites , to receive usual care by physicians or to receive an integrated multi-component CVD risk reduction intervention . The intervention involves electronic health record management , decision-support prompts to the healthcare team , and the support of a care coordinator to actively facilitate patient and provider adherence to evidence -based guidelines . The primary outcome is a composite of multiple CVD risk factor control ( blood glucose and either blood pressure or cholesterol , or all three ) . Other outcomes include control of the individual CVD risk factors , process and patient-centered measures , cost-effectiveness , and acceptability/feasibility . CONCLUSION The CARRS Translation Trial tests a low-cost diabetes care delivery model in urban South Asia to achieve comprehensive cardio-metabolic disease case-management of high-risk patients ( clinical trials.gov number : NCT01212328 ) OBJECTIVE The aim of this study was to examine both single and joint associations of physical activity and conventional cardiovascular risk factors with total and cardiovascular mortality among patients with diabetes . RESEARCH DESIGN AND METHODS We prospect ively followed 3,708 Finnish patients with type 2 diabetes aged 25 - 74 years .  Physical activity , smoking status , blood pressure , height , weight , and serum cholesterol level were determined at baseline . Cox proportional hazard models were used to estimate single and joint effects of physical activity and other cardiovascular risk factors on the risk of mortality . RESULTS During a mean follow-up of 18.7 years , 1,423 deaths were recorded , 906 of which were due to cardiovascular disease . Moderate or high levels of physical activity were associated with decreased total and cardiovascular mortality , whereas higher levels of BMI and blood pressure and current smoking were associated with increased total and cardiovascular mortality . High serum cholesterol levels also increased cardiovascular mortality . The protective effect of physical activity was consistent in diabetic patients with any levels of BMI , blood pressure , total cholesterol , and smoking . CONCLUSIONS A moderate or high level of physical activity was associated with a reduced risk of total and cardiovascular mortality among patients with type 2 diabetes . The favorable association of physical activity with longevity was observed regardless of the levels of BMI , blood pressure , total cholesterol , and smoking The Australian Therapeutic Trial in Mild Hypertension was a controlled trial in which mildly hypertensive patients , aged between 35 and 65 years ( diastolic blood pressure 95 - 109 ) were r and omly assigned to take antihypertensive drugs or matched placebos  for periods of up to 6 years . The overall data showed that the treated group had a lower incidence of both death and of nonfatal cardiovascular events . The differences in the incidence of noncardiovascular deaths did not differ significantly between the two groups . Univariate analysis of possible prognostic factors at the time of entry into the study showed a higher incidence of trial endpoints -- mostly events due to ischemic heart disease and cerebrovascular disease -- in older subjects , men , cigarette smokers and those with higher systolic blood pressures , and in thinner subjects than in others . There was a lower incidence of these events in actively treated persons than in control subjects at each level of incidence of each covariate measured . Treatment benefit was greatest in persons with lower systolic blood pressures and lower serum cholesterol levels . Multivariate regression analyses confirmed that the incidence of trial endpoints increased with age and with systolic blood pressures . There was a higher incidence in smokers than in nonsmokers , especially in those with low body weights . Treatment benefited thin smokers most , and the effects of treatment seemed to be reduced in those with higher serum cholesterol levels . There was a substantial fall in blood pressure in many of the placebo group Objective : To determine the prognosis of treated hypertensive type 1 ( insulin-dependent ) diabetic patients with overt nephropathy . Design : A controlled , prospect i ve , parallel , 5-year follow-up trial . Setting : The tertiary care centre of the Heinrich Heine University Hospital in Dusseldorf , Germany . Patients and interventions : A sequential sample of 91 hypertensive patients with overt diabetic nephropathy participated in a diabetes treatment programme . Thereafter 45 patients received intensified antihypertensive therapy including blood pressure self-monitoring and self-adjustment of antihypertensive drug treatment with the goal of permanent normalization of blood pressure values below 140/90 mmHg . The remaining 46 patients were administered routine antihypertensive therapy and formed the control group . At baseline both groups were comparable in age , sex , metabolic control and renal function . The groups differed at baseline in their duration of diabetes and blood pressure values , which were higher in the intensified antihypertensive therapy group . Outcome measures : Total mortality and the need for renal replacement therapy . Main results : Blood pressure control was significantly improved in patients who were subjected to intensified antihypertensive therapy , whereas it deteriorated in the group of patients who received routine antihypertensive therapy . At follow-up , primary end points of the study occurred in five ( 11 % ) patients of the intensified therapy group and in 19 ( 41 % ) patients of the routine therapy group . According to life table analysis , intensified antihypertensive therapy was associated with less frequent primary end points ( P= 0.0058 ) and longer survival ( P=0.01 ) . The differences between the groups remained significant after adjustment for covariates in the proportional hazards model . Conclusion : Participation in a treatment programme aim ed at intensification of antihypertensive therapy is associated with a reduction of mortality in hypertensive type 1 diabetic patients with overt nephropathy AIMS AND OBJECTIVES To determine the effectiveness of an electronic messaging support service for management of cardiovascular risk factors in patients with diabetes . BACKGROUND Microletter and short message service are widely used , but their health education benefit for people with type 2 diabetes mellitus has not been investigated . DESIGN Convenience sample study with r and omised group assignment . METHODS Participants completed survey question naires , physical and laboratory evaluations between May 2015 and May 2016 and were then r and omly assigned to two groups for receipt of a microletter + short message or a phone call ( control ) . Appointment reminders and health information were sent to the intervention patients by microletter + short message . Every three months , intervention patients and control patients were followed up by telephone . After 12 months , changes in cardiovascular risk factors in each group were evaluated and compared . RESULTS There were no statistically significant changes or between-group differences in daily smoking and drinking . There were statistically significant between-group differences in glycated haemoglobin ( p = .034 ) , postpr and ial plasma glucose ( p = .001 ) , postpr and ial insulin ( p = .005 ) , total cholesterol ( p = .038 ) and low-density lipoprotein ( p < .001 ) . Levels of glycated haemoglobin ( p = .011 ) , fasting plasma glucose ( p = .007 ) , postpr and ial plasma glucose ( p < .001 ) , fasting insulin ( p = 0.004 ) , postpr and ial insulin ( p < .001 ) , total cholesterol ( p < .001 ) and low-density lipoprotein ( p < .001 ) were found to be decreased significantly in intervention patients . Systolic blood pressure decreased significantly in patients only followed by telephone ( p = .014 ) . The microletter + short message intervention was an effective means of reducing cardiovascular risk in patients with type 2 diabetes mellitus . CONCLUSION Regular smartphone communication had a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus . RELEVANCE TO CLINICAL PRACTICE Regular smartphone communication has a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus BACKGROUND Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors . METHODS The Systolic Hypertension in the Elderly Program was a community-based , multicenter , r and omized , double-blind , placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older . This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program , including changes in serum chemistry test results in a subgroup for 3 years . Patients were r and omized to receive placebo or treatment with active drugs , with the dose increased in stepwise fashion if blood pressure control goals were not attained : step 1 , 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone ; and step 2 , the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo . RESULTS After 3 years , the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group ( both groups , P<.001 ) . New cases of diabetes were reported by 8.6 % of the participants in the active treatment group and 7.5 % of the participants in the placebo group ( P=.25 ) . Small effects of active treatment compared with placebo were observed with fasting levels of glucose ( + 0.20 mmol/L [ + 3.6 mg/dL ] ; P<.01 ) , total cholesterol ( + 0.09 mmol/L [ + 3.5 mg/dL ] ; P<.01 ) , high-density lipoprotein cholesterol ( -0.02 mmol/L [ -0.77 mg/dL ] ; P<.01 ) and creatinine ( + 2.8 micromol/L [ + 0.03 mg/dL ] ; P<.001 ) . Larger effects were seen with fasting levels of triglycerides ( + 0.9 mmol/L [ + 17 mg/dL ] ; P<.001 ) , uric acid ( + 35 micromol/L [ + .06 mg/dL ] ; P<.001 ) , and potassium ( -0.3 mmol/L ; P<.001 ) . No evidence was found for a subgroup at higher risk of risk factor changes with active treatment . CONCLUSIONS Antihypertensive therapy with low-dose chlorthalidone ( supplemented if necessary ) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients BACKGROUND Regular exercise has been associated in prospect i ve studies with reduced incidence of  cardiovascular disease ( CVD ) and death  . OBJECTIVE To assess in a cohort study whether there is a similar protective effect of regular exercise among hypertensive individuals . DESIGN Population -based prospect i ve cohort study . Spare time physical activity was assessed by structured interview . SETTING Malmo , Sweden . PARTICIPANTS Healthy men ( n = 642 ) born in 1914 . A baseline examination took place in 1969 - 1970 . MAIN OUTCOME MEASURES All-cause and cardiovascular mortality rates during 25 years of follow-up in relation to blood pressure and other risk factors for atherosclerosis . RESULTS One-hundred ( 16 % ) men reported vigorous spare time physical activity . In this group , 31 had hypertension ( blood pressure > 160/95 mm Hg or treatment for hypertension ) , 47 were smokers and 39 had hyperlipidaemia . Among the 173 men with hypertension , vigorous physical activity was associated with markedly reduced rates of all-cause ( 17.3 versus 40.0 deaths per 1000 person-years ) and cardiovascular mortality ( 6.3 versus 21.0 deaths per 1000 person-years ) . The risk reductions associated with exercise remained statistically significant after adjustment for smoking , systolic blood pressure and antihypertensive therapy . The relative risk was 0.43 ( confidence interval 0.22 - 0.82 ) for total mortality and 0.33 ( confidence interval 0.11 -0.94 ) for CVD mortality . CONCLUSION People who regularly perform physical activity constitute a heterogeneous group with regard to their exposure to known cardiovascular risk factors . Our results support the view that regular physical activity is associated with a reduced incidence of cardiovascular disease and death and suggest that this protective effect may be enhanced among hypertensive individuals AIM To compare three methods of assessing 5-year absolute risk of cardiovascular disease ( CVD ) in adults with type 2 diabetes ; the Framingham CVD equation , the UK Prospect i ve Diabetes Study ( UKPDS ) coronary heart disease plus stroke equations and the New Zeal and Guidelines Group (NZGG)-modified Framingham CVD equation . METHODS Participants were 423 people with newly ( n=118 ) or previously diagnosed ( n=305 ) Type 2 diabetes mellitus aged 35 to 74 years with no past history of cardiovascular disease or nephropathy from an interviewed study population of 4049 adults .  Absolute 5-year CVD risks were calculated in 5-year age b and s by gender ; Maori , Pacific , and European ethnicity ; and newly and previously diagnosed diabetes . RESULTS The mean 5-year CVD risk score was 2.9 % ( 95%CI : 2.40 - 3.42 ; p<0.0001 ) lower for the UKPDS risk engine compared to the original Framingham equation in absolute terms , and 7.6 % ( 95%CI : 7.05 - 8.08 ; p<0.0001 ) lower than the NZGG-modified Framingham equation . In general , 5-year CVD risks were highest using the NZGG-modified equation , intermediate using the original Framingham equation and lowest using the combined UKPDS coronary heart disease plus stroke equations , in all age groups by gender , ethnicity , and time of diagnosis of Type 2 diabetes . However , the 5-year CVD risks are themselves potentially low as they include treated blood pressure and lipid values . Compared to the UKPDS 15 % level of risk , the NZ Guidelines modified 15 % level of risk results in people with diabetes being recommended for CVD drug management 10 to 17 years earlier . CONCLUSIONS In general , among people with Type 2 diabetes , the Framingham equations showed higher 5-year CVD risk estimates compared to combined UKPDS coronary heart disease plus stroke equations and the NZGG-modified Framingham equation showed the highest 5-year CVD risks . In practice , people with type 2 diabetes will be managed earlier and more intensively based on their risk estimated by the current NZGG guidelines than if the UKPDS or original Framingham equations were used The prevalence of hypertension in type 2 diabetics is high , though there is no published data for Switzerl and . This prospect i ve cohort survey determined the frequency of type 2 diabetes mellitus associated with hypertension from medical practitioners in Switzerl and , and collected data on the diagnostic and therapeutic work‐up for cardiovascular risk patients . The Swiss Hypertension And Risk Factor Program ( SHARP ) is a two‐part survey : The first part , I‐SHARP , was a survey among 1040 Swiss physicians to assess what are the target blood pressure ( BP ) values and preferred treatment for their patients . The second part , SHARP , collected data from 20,956 patients treated on any of 5 consecutive days from 188 participating physicians . In I‐SHARP , target BP⩽135/85 mmHg , as recommended by the Swiss Society of Hypertension , was the goal for 25 % of physicians for hypertensives , and for 60 % for hypertensive diabetics ; values > 140/90 mmHg were targeted by 19 % for hypertensives , respectively 9 % for hypertensive diabetics . In SHARP , 30 % of the 20,956 patients enrolled were hypertensive ( as defined by the doctors ) and 10 % were diabetic ( 67 % of whom were also hypertensive ) . Six per cent of known hypertensive patients and 4 % of known hypertensive diabetics did not receive any antihypertensive treatment . Diabetes was not treated pharmacologically in 20 % of diabetics . Proteinuria was not screened for in 45 % of known hypertensives and in 29 % of known hypertensive diabetics . In Switzerl and , most physicians set target BP levels higher than recommended in published guidelines . In this country with easy access to medical care , high medical density and few financial constraints , appropriate detection and treatment for cardiovascular risk factors remain highly problematic BACKGROUND AND PURPOSE The Systolic Hypertension in the Elderly Program ( SHEP ) demonstrated a significant reduction in stroke and coronary event rates among participants r and omly assigned to active blood pressure treatment . Selected participants were evaluated for peripheral atherosclerosis and followed up for cardiovascular events beyond the end of the SHEP trial . Antihypertensive treatment effects were evaluated based on the presence or absence of clinical or sub clinical atherosclerosis . METHODS As an ancillary study to SHEP , 190 participants at the Pittsburgh center were evaluated for peripheral atherosclerosis , defined as either an internal carotid stenosis ( by duplex scan ) or lower extremity arterial disease ( identified by ankle blood pressure ) . Participants were subsequently followed up for cardiovascular events . RESULTS Estimates of 4-year mortality rates were 4.8 % for participants with no atherosclerosis , 16.7 % for those with sub clinical atherosclerosis , and 23 % among those with clinical evidence of atherosclerosis ( P < .001 ) . Fatal plus nonfatal cardiovascular event rates were 10.9 % , 29.8 % , and 58.3 % for the three groups , respectively ( P < .001 ) . Differences remained significant after adjustment for age , sex , treatment assignment , smoking , and high-density lipoprotein cholesterol . Individuals assigned to placebo at the beginning of SHEP had higher cardiovascular event rates than individuals assigned to active treatment ( P = .011 ) , with the most striking difference 3 or more years after the end of the SHEP trial . When this analysis was stratified by the presence or absence of detectable atherosclerosis , the absolute treatment effect was largest among those with evidence of disease . CONCLUSIONS Individuals with systolic hypertension and evidence of peripheral atherosclerosis are at high risk for cardiovascular events . Targeting this group for antihypertensive therapy would result in the prevention of a large number of cardiovascular events A study protocol for a double-blind r and omised control trial of hypotensive treatment in elderly hypertensive patients has been tested in a number of pilot centres throughout Europe . It was shown that this study is possible from the logistic point of view . In these elderly patients , hydrochlorothiazide + triamterene treatment with or without methyldopa , maintained a significant hypotensive effect in the absence of major electrolyte disturbances . The initiation of hypotensive therapy did not provoke an excess of cardiovascular complications . The influence of hypotensive therapy on the general well-being and on the morbidity and the mortality of elderly patients with high blood pressure , is thereby being assessed . The study will continue for 5 years and other centres are invited to join Background Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension , contributing to cardiovascular complications . Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness , and is an important contributing factor for hypertension . Since the sodium glucose cotransport-2 ( SGLT2 ) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus , we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity . Methods Blood pressure , arterial stiffness , heart rate variability ( HRV ) and circulating adrenergic mediators were measured during clamped euglycaemia ( blood glucose 4–6 mmol/L ) and hyperglycaemia ( blood glucose 9–11 mmol/L ) in 40 normotensive type 1 diabetes mellitus patients . Studies were repeated after 8 weeks of empagliflozin ( 25 mg once daily ) . Results In response to empagliflozin during clamped euglycaemia , systolic blood pressure ( 111 ± 9 to 109 ± 9 mmHg , p = 0.02 ) and augmentation indices at the radial ( -52 % ± 16 to -57 % ± 17 , p = 0.0001 ) , carotid ( + 1.3 ± 1 7.0 to -5.7 ± 17.0 % , p < 0.0001 ) and aortic positions ( + 0.1 ± 13.4 to -6.2 ± 14.3 % , p < 0.0001 ) declined . Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition . Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions ( p ≤ 0.0001 ) , while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia ( 5.7 ± 1.1 to 5.2 ± 0.9 m/s , p = 0.0017 ) . HRV , plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions . Conclusions Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects . The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition , including glucose lowering , antihypertensive and weight reduction effects . Trial registration Clinical trial registration : Cardiovascular morbidity , including coronary artery disease and left ventricular hypertrophy , and mortality are high in patients following renal transplantation . Cardiovascular disease is thought to be due to traditional ( hypertension , hyperlipidemia , diabetes mellitus and smoking ) as well as nontraditional cardiovascular risk factors ( microinflammation ) . Furthermore , immunosuppressive drugs , namely , calcineurin inhibitors , sirolimus , and steroids , have been reported to adversely affect cardiovascular risk factors ( e.g. , hypertension , hyperlipidemia , hyperglycemia ) . Evidence from comparative trials and from conversion studies suggest that blood pressure , hyperlipidemia , and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus . In the European Tacrolimus versus  Cyclosporin A Microemulsion Renal Transplantation Study , 557 patients were r and omly allocated to therapy with tacrolimus  ( n = 286 ) versus cyclosporine ( n = 271 ) . In addition , to blood pressure , serum cholesterol , HDL cholesterol , triglycerides , and blood glucose , we estimated the 10-year risk of coronary heart disease ( Framingham risk score ) . Tacrolimus result ed in a significantly lower time-weighted average of serum cholesterol ( P < .001 ) , and mean arterial blood pressure ( P < .05 ) , but a higher time-weighted average of blood glucose ( P < .01 ) than cyclosporine .  Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus , ( 10.0 % versus 13.2 % ; P < .01 ) but was unchanged in women ( 4.7 % versus 7.0 % ) . Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease The relationship between serum uric acid ( SUA ) and risk of coronary heart disease ( CHD ) mortality remains controversial , particularly in diabetic subjects . The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors . Five hundred and eighty-one subjects aged ≥65 years with non-insulin-dependent diabetes mellitus were prospect ively studied in the frame of the CArdiovascular STudy in the ELderly ( CASTEL ) . Historical and clinical data , blood tests and 12-year fatal events were recorded . SUA as a continuous item was divided into tertiles and , for each tertile , adjusted relative risk ( RR ) with 95 % confidence intervals ( CI ) was derived from multivariate Cox analysis . CHD mortality was predicted by SUA in a J-shaped manner . Mortality rate was 7.9 % ( RR 1.28 , CI 1.05–1.72 ) , 6.0 % ( reference tertile ) and 12.1 % ( RR 1.76 , CI 1.18–2.27 ) in the increasing tertiles of SUA , respectively , without any difference between genders . In diabetic elderly subjects , SUA independently predicts the risk of CHD mortality in a J-shaped manner The antihypertensive effect of indapamide has never been clearly understood , particularly in hypertensive patients with diabetes mellitus . A total of 565 patients were r and omly selected to receive either indapamide 1.5 mg or enalapril 10 mg daily for 12 months . Brachial blood pressure ( BP ) and plasma and urinary electrolytes were measured at baseline and at the end of follow-up . Sodium and potassium levels and excretion rates were measured in overnight urine collection s. After 12 months ' treatment , similar significant reductions were observed in systolic and diastolic BP and pulse pressure levels in both treatment arms ( P < .001 ) . However , age , body mass index , diabetes duration , and plasma sodium reductions were shown to be major , independent factors influencing BP reduction with indapamide , but not with enalapril . Regression coefficients were positive for age and plasma sodium reductions ( P ≤ .009 ) but negative for body mass index and diabetes duration ( P ≤ .008 ) . Similar findings were observed for pulse pressure . These results were more notable in elderly patients , did not differ regardless of whether BP reduction was measured in absolute or percent values , and were associated with increased sodium and potassium excretion rates . Indapamide is more effective than enalapril at reducing BP in elderly diabetic hypertensives with marked sodium retention OBJECTIVES To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome ( ACS ) . DESIGN Prospect i ve cohort study . SETTING Twenty-three hospitals in Italy . PARTICIPANTS Individuals aged 75 and older with non-ST-elevation ACS ( NSTEACS ) ( mean age 82 , 47 % female ) ( N = 645 ) .  MEASUREMENTS Diabetic status and blood glucose levels were assessed on admission . Hyperglycemia was defined as glucose greater than 140 mg/dL. Multivariable Cox proportional hazard regression was used to assess the potential confounding effect of major covariates on the association between diabetic status , admission glucose , and 1-year mortality . RESULTS A history of diabetes mellitus was found in 231 participants ( 35.8 % ) , whereas 257 ( 39.8 % ) had hyperglycemia . Hyperglycemia was found in 171 participants with diabetes mellitus ( 70 % ) and 86 ( 21 % ) without diabetes mellitus . Participants with diabetes mellitus were significantly ( P < .05 ) more likely to have had prior myocardial infa rct ion and stroke and had lower ejection fraction and blood hemoglobin . Hyperglycemia was associated with lower ( P < .05 ) ejection fraction and estimated glomerular filtration rate ( eGFR ) . Diabetic status and hyperglycemia were associated with greater 1-year mortality according to univariate analysis ( 54 participants with diabetes mellitus died ( 23.4 % ) , versus 66 ( 15.9 % ) without diabetes mellitus ( hazard ratio ( HR ) = 1.5 95 % confidence interval ( CI ) = 1.0 - 2.1 ) , and 60 participants with hyperglycemia died ( 23.3 % ) , versus 60 ( 15.5 % ) without hyperglycemia ( HR=1.6 ; 95 % CI = 1.1 - 2.2 ) , but this association was not statistically significant after adjustment for ejection fraction , age , blood hemoglobin , and eGFR . CONCLUSION In elderly adults with NSTEACS , diabetes mellitus and hyperglycemia on admission are associated with higher mortality , mostly because of preexisting cardiovascular and renal damage IMPORTANCE Coronary artery disease ( CAD ) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus , yet CAD often is asymptomatic prior to myocardial infa rct ion ( MI ) and coronary death . OBJECTIVE To assess whether routine screening for CAD by coronary computed tomography angiography ( CCTA ) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy  would reduce the risk of death and nonfatal coronary outcomes . DESIGN , SETTING , AND PARTICIPANTS The FACTOR-64 study was a r and omized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years ' duration and without symptoms of CAD were recruited from 45 clinics and practice s of a single health system ( Intermountain Healthcare , Utah ) , enrolled at a single-site coordinating center , and r and omly assigned to CAD screening with CCTA ( n = 452 ) or to st and ard national guidelines -based optimal diabetes care ( n = 448 ) ( targets : glycated hemoglobin level < 7.0 % , low-density lipoprotein cholesterol level < 100 mg/dL , systolic blood pressure < 130 mm Hg ) . All CCTA imaging was performed at the coordinating center . St and ard therapy or aggressive therapy ( targets : glycated hemoglobin level < 6.0 % , low-density lipoprotein cholesterol level < 70 mg/dL , high-density lipoprotein cholesterol level > 50 mg/dL [ women ] or > 40 mg/dL [ men ] , triglycerides level < 150 mg/dL , systolic blood pressure < 120 mm Hg ) , or aggressive therapy with invasive coronary angiography , was recommended based on CCTA findings . Enrollment occurred between July 2007 and May 2013 , and follow-up extended to August 2014 . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of all-cause mortality , nonfatal MI , or unstable angina requiring hospitalization ; the secondary outcome was ischemic major adverse cardiovascular events ( composite of CAD death , nonfatal MI , or unstable angina ) . RESULTS At a mean follow-up time of 4.0 ( SD , 1.7 ) years , the primary outcome event rates were not significantly different between the CCTA and the control groups ( 6.2 % [ 28 events ] vs 7.6 % [ 34 events ] ; hazard ratio , 0.80 [ 95 % CI , 0.49 - 1.32 ] ; P = .38 ) . The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups ( 4.4 % [ 20 events ] vs 3.8 % [ 17 events ] ; hazard ratio , 1.15 [ 95 % CI , 0.60 - 2.19 ] ; P = .68 ) . CONCLUSIONS AND RELEVANCE Among asymptomatic patients with type 1 or type 2 diabetes , use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality , nonfatal MI , or unstable angina requiring hospitalization at 4 years . These findings do not support CCTA screening in this population . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00488033 Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events OBJECTIVES This report presents information on the effects of aspirin on mortality , the occurrence of cardiovascular events , and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study ( ETDRS ) . STUDY DESIGN This multicenter , r and omized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute . PATIENTS Patients ( N = 3711 ) were enrolled in 22 clinical centers between April 1980 and July 1985 . Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible . Approximately 30 % of all patients were considered to have type I diabetes mellitus , 31 % type II , and in 39 % type I or II could not be determined definitely . INTERVENTION Patients were r and omly assigned to aspirin or placebo ( two 325-mg tablets once per day ) . MAIN OUTCOME MEASURES Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin . Other outcome variables included cause-specific mortality and cardiovascular events . RESULTS The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 ( 99 % confidence interval , 0.75 to 1.11 ) . Larger differences were noted for the occurrence of fatal and nonfatal myocardial infa rct ion ; the estimate of relative risk was 0.83 for the entire follow-up period ( 99 % confidence interval , 0.66 to 1.04 ) . CONCLUSIONS The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons . Furthermore , there was no evidence of harmful effects of aspirin . Aspirin has been recommended previously for persons at risk for cardiovascular disease . The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease NORDIL -- the Nordic Diltiazem Study (NORDIL)--is a prospect i ve , r and omized , open blinded-endpoint ( PROBE ) , multicenter , parallel-group morbidity/mortality outcome study in hypertensive patients design ed to compare an intervention strategy based on the calcium antagonist diltiazem with a strategy based on conventional antihypertensive drug treatment ( diuretics or beta-adrenergic blockers ) .  Patient recruitment was started in Norway and Sweden in September 1992 , and ended on December 15 , 1996 , when 10.896 male and female patients , aged 50 - 74 years , with essential hypertension had been r and omized . In this paper we describe the baseline data of the patient cohort and blood pressures achieved in the two treatment groups during the early part of the study . The patient cohort consists of 5294 males and 5602 females with a mean age of 59.6 and 60.3 years , respectively . Concomitant disorders and risk factors in the cohort are : smoking 22 % , ischemic heart disease 3.0 % , previous myocardial infa rct ion ( MI ) 2.0 % , previous stroke 1.5 % , diabetes mellitus 7.0 % , and renal impairment 0.3 % . There were no differences between the treatment groups in these respects . The blood pressure treatment goal is a target diastolic blood pressure of < or = 90 mmHg or a 10 % diastolic blood pressure reduction from the inclusion pressure . In the treatment group r and omized to a diltiazem-based treatment strategy , blood pressure was 174/106 mmHg at baseline and 156/90 mmHg after 12 months of follow-up on active treatment . In the group r and omized to a conventional treatment strategy , baseline blood pressure at r and omization was 173/106 mmHg and 153/90 mmHg after 12 months on active therapy . The NORDIL study will terminate on October 31 , 1999 and the final results should be available by mid-2000
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
OBJECTIVE To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus , at different blood pressure levels .