Appropriate Blood Pressure Control in NIDDM (ABCD) Trial The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2 Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. The ABCD (Appropriate Blood Pressure Control in Diabetes) trial. Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes. Effect of nurse-directed hypertension treatment among First Nations people with existing hypertension and diabetes mellitus: the Diabetes Risk Evaluation and Microalbuminuria (DREAM 3) randomized controlled trial Development of diabetes is retarded by ACE inhibition in hypertensive patients – a subanalysis of the Captopril Prevention Project (CAPPP) Effect of antihypertensive therapy on progression of carotid intima-media thickness in patients with type 2 diabetes mellitus. The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes Rosiglitazone for type 2 diabetes mellitus. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy Stepwise screening for diabetes identifies people with high but modifiable coronary heart disease risk. The ADDITION study Antihypertensive treatment efficacy in type II diabetes mellitus. Dissociation between casual and 24-hour ambulatory blood pressure. Spanish Multicenter Study Group. Appropriate Blood Pressure Control in type II diabetes (ABCD Trial): implications for complications. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) analyses performed up to 1992. Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.
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
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 .