title: Randomised Double-Blind Comparison of Placebo and Active Drugs for Effects on Risks Associated with Blood Pressure Variability in the Systolic Hypertension in Europe Trial Treating hypertension in the older person: an evaluation of the association of blood pressure level and its reduction with cognitive performance. Does lowering the blood pressure improve the mood? Quality-of-life results from the Hypertension Optimal Treatment (HOT) study. Shanghai trial of nifedipine in the elderly (STONE). Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly: Valsartan in Elderly Isolated Systolic Hypertension Study Quality of life on randomized treatment for isolated systolic hypertension: results from the Syst-Eur Trial Treatment of hypertension in patients 80 years of age or older. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group. Intensive Blood Pressure Control, Falls, and Fractures in Patients with Type 2 Diabetes: The ACCORD Trial Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Principal Results of the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension The effect of prescribed daily dose frequency on patient medication compliance. The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET). Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial Effects of intensive blood-pressure control in type 2 diabetes mellitus. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. Mortality and Morbidity Results from the European Working Party on High Blood Pressure in the Elderly Trial Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial.
abstract: Background In the Systolic Hypertension in Europe trial ( NCT02088450 ) , we investigated whether systolic blood pressure variability determines prognosis over and beyond level . Methods Using a computerised r and om function and a double-blind design , we r and omly allocated 4695 patients ( ≥60 years ) with isolated systolic hypertension ( 160–219/<95 mm Hg ) to active treatment or matching placebo . Active treatment consisted of nitrendipine ( 10–40 mg/day ) with possible addition of enalapril ( 5–20 mg/day ) and /or hydrochlorothiazide ( 12.5–25.0 mg/day ) . We assessed whether on-treatment systolic blood pressure level ( SBP ) , visit-to-visit variability independent of the mean ( VIM ) or within-visit variability ( WVV ) predicted total ( n = 286 ) or cardiovascular ( n = 150 ) mortality or cardiovascular ( n = 347 ) , cerebrovascular ( n = 133 ) or cardiac ( n = 217 ) endpoints . Findings At 2 years , mean between-group differences were 10.5 mm Hg ( p<0.0001 ) for SBP , 0.29 units ( p = 0.20 ) for VIM , and 0.07 mm Hg ( p = 0.47 ) for WVV . Active treatment reduced ( p≤0.048 ) cardiovascular ( −28 % ) , cerebrovascular ( −40 % ) and cardiac ( −24 % ) endpoints . In analyses dichotomised by the median , patients with low vs. high VIM had similar event rates ( p≥0.14 ) . Low vs. high WVV was not associated with event rates ( p≥0.095 ) , except for total and cardiovascular mortality on active treatment , which were higher with low WVV ( p≤0.0003 ) . In multivariable-adjusted Cox models , SBP predicted all endpoints ( p≤0.0043 ) , whereas VIM did not predict any ( p≥0.058 ) . Except for an inverse association with total mortality ( p = 0.042 ) , WVV was not predictive ( p≥0.15 ) . Sensitivity analyses , from which we excluded blood pressure readings within 6 months after r and omisation , 6 months prior to an event or both were confirmatory . Conclusions The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP . Higher blood pressure level , but not higher variability , predicted risk . Trial Registration Clinical Trials.gov No adverse effect upon cognitive function has been detected during the first 9 months of treatment by a thiazide diuretic ( Moduretic ; Merck Sharp & Dohme , Hoddesdon , UK ) or a beta-blocking agent ( atenolol ) of moderately elevated blood pressure in a cohort of 2630 men and women aged between 65 and 74 years . Furthermore , no association was discovered between levels of systolic or diastolic blood pressure at outset and responses to st and ard tests of cognitive function . This study was carried out in general practice s as part of the current Medical Research Council Treatment Trial of Mild Hypertension in the Elderly Nine-hundred- and -twenty-two hypertensive patients were included in a sub study to the Hypertension Optimal Treatment study , which aim ed to investigate the impact on quality of life of lowering the pressure and of intensified therapy .  Seven-hundred- and -eighty-one patients completed both baseline and follow-up question naires ( intention-to-treat population ) , while 610 patients were included in a per protocol analysis . Patients were r and omized to three diastolic BP levels ( DBPs ) , i.e. < or = 90 mmHg , < or = 85 mmHg and < or = 80 mmHg . Two self-administered vali date d question naires , the  Psychological General Well-Being index and the Subjective Symptoms Assessment Profile ( SSA-P )  were completed at baseline and after 6 months . The lower the DBP achieved , the greater the improvement in well-being ( p < 0.05 ) . The increase in well-being from baseline to 6 months was significant in target groups < or = 80 mmHg ( p < 0.01 ) and < or = 85 mmHg ( p < 0.05 ) . The SSA-P domains , cardiac symptoms and dizziness improved in all groups but the sex life score deteriorated in the < or = 80 and < or = 85 mmHg groups in male patients . In all target groups , headaches were reduced ( p < 0.001 ) , while swollen ankles ( p < 0.001 ) and dry cough in the < or = 80 mmHg group ( p < 0.001 ) increased . Although more intensive antihypertensive therapy is associated with a slight increase in subjective symptoms , it is nonetheless still associated with improvements in patients ' well-being OBJECTIVE To assess the effectiveness of nifedipine treatment in elderly hypertensives . METHODS A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60 - 79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months . Clinical events and risk modification were analysed in collaboration with the University of Montreal . Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in . RESULTS Cox 's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events : ' original treatment assignment ' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group . Similar significance s were achieved with ' actual treatment ' or ' changes excluded ' ( excluding reallocated subjects ) analyses . A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 ( 95 % confidence interval 0.27 - 0.61 ) . CONCLUSION Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets Objective To compare quality of life in elderly patients with isolated systolic hypertension allocated r and omly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial . Design Double-blind r and omized controlled trial . Methods Patients aged 60 years were allocated r and omly to groups to receive first-line treatment with nitrendipine ( with second- and third-line enalapril and hydrochlorothiazide ) or placebo . Trained interviewers administered trail-making tests ( Trail A and B ) , Brief Assessment Index ( a measure of depressed mood ) and four subscales from the Sickness Impact Profile ( Ambulation , Social Interaction , Sleep and Rest , and Home work ) . Results Six hundred and ten patients completed a baseline and at least one follow-up question naire . Trail-making scores were slower in actively treated patients , especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [ 95 % confidence interval ( CI ) 0.07 to 0.43 ] for Trail-making A and 0.13 ( 95 % CI −0.05 to 0.31 ) for Trail-making B. Across the 4 years of follow-up , patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients ( odds ratio 1.32 , 95 % CI 1.02 to 1.69 ) , equivalent to a 7 % difference . There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression .  Conclusions Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo .  The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to < 24 points or a drop of three points in 1 year ) were assessed by st and ard diagnostic criteria and expert review . The trial was stopped in 2007 at the second interim analysis after treatment result ed in a reduction in stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p<0.0001 ; and diastolic -5.9 mm Hg , p<0.0001 . There were 263 incident cases of dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment  in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia Objective To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy  , and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials . Methods The Felodipine Event Reduction ( FEVER ) trial was an investigator- design ed , prospect i ve , multicentre , double-blind , r and omized , placebo-controlled , parallel group trial . It enrolled 9800 Chinese patients , of either sex , aged 50–79 years , with one or two additional cardiovascular risk factors or disease , whose blood pressure , 6 weeks after switching from previous antihypertensive therapy to low-dose ( 12.5 mg a day ) hydrochlorothiazide , was in the range 140–180 mmHg ( systolic ) or 90–100 mmHg ( diastolic ) . These patients were r and omly assigned either to low-dose felodipine extended release or placebo , and followed at 3-month intervals for an average of 40 months . Results The intention-to-treat analysis included 9711 r and omly selected patients with only 30 ( 0.3 % ) lost to follow-up . A total of 31 842 patient-years of follow-up were accumulated , with 85.9 % of patients remaining on blinded r and omized treatment . Add-on therapy was given to 33.9 % of the hydrochlorothiazide – felodipine patients and to 42.3 % of the hydrochlorothiazide – placebo patients . In the felodipine  group , systolic blood pressure (SBP)/diastolic blood pressure ( DBP ) decreased ( from r and omization to study end ) from 154.2/91.0 to 137.3/82.5 mmHg , and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg , with an average difference throughout the trial of 4.2/2.1 mmHg . In the felodipine group , the primary endpoint ( fatal and non-fatal stroke ) was reduced by 27 % ( P = 0.001 ) . Among secondary endpoints , all cardiovascular events were reduced by 27 % ( P < 0.001 ) , all cardiac events by 35 % ( P = 0.012 ) , death by any cause by 31 % ( P = 0.006 ) , coronary events by 32 % ( P = 0.024 ) , heart failure by 30 % ( P = 0.239 ) , cardiovascular death by 33 % ( P = 0.019 ) , cancer by 36 % ( P = 0.017 ) in the felodipine group . No significant differences were found in new-onset diabetes . Both treatments were very well tolerated . Conclusions In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg , such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide , is associated with very substantial reductions in the incidence of most types of cardiovascular events . As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg , and SBP in the placebo group was slightly above that level , FEVER provides the required evidence in support of the guidelines recommended goal , even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events BACKGROUND Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes , and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension . We assessed the effects of the routine administration of an angiotensin converting enzyme ( ACE ) inhibitor-diuretic combination on serious vascular events in patients with diabetes , irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs . METHODS The trial was done by 215 collaborating centres in 20 countries . After a 6-week active run-in period , 11 140 patients with type 2 diabetes were r and omised to treatment with a fixed combination of perindopril and indapamide or matching placebo , in addition to current therapy . The primary endpoints were composites of major macrovascular and microvascular events , defined as death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion , and new or worsening renal or diabetic eye disease , and analysis was by intention-to-treat . The macrovascular and microvascular composites were analysed jointly and separately . This trial is registered with Clinical Trials.gov , number NCT00145925 . FINDINGS After a mean of 4.3 years of follow-up , 73 % of those assigned active treatment and 74 % of those assigned control remained on r and omised treatment . Compared with patients assigned placebo , those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg . The relative risk of a major macrovascular or microvascular event was reduced by 9 % ( 861 [ 15.5 % ] active vs 938 [ 16.8 % ] placebo ; hazard ratio 0.91 , 95 % CI 0.83 - 1.00 , p=0.04 ) . The separate reductions in macrovascular and microvascular events were similar but were not independently significant ( macrovascular 0.92 ; 0.81 - 1.04 , p=0.16 ; microvascular 0.91 ; 0.80 - 1.04 , p=0.16 ) . The relative risk of death from cardiovascular disease was reduced by 18 % ( 211 [ 3.8 % ] active vs 257 [ 4.6 % ] placebo ; 0.82 , 0.68 - 0.98 , p=0.03 ) and death from any cause was reduced by 14 % ( 408 [ 7.3 % ] active vs 471 [ 8.5 % ] placebo ; 0.86 , 0.75 - 0.98 , p=0.03 ) . There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline . INTERPRETATION Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events , including death . Although the confidence limits were wide , the results suggest that over 5 years , one death due to any cause would be averted among every 79 patients assigned active therapy The Systolic Hypertension in Europe ( Syst-Eur ) trial proved that blood pressure ( BP ) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older ( ⩾60 years ) patients with isolated systolic hypertension ( systolic BP ⩾160 mm Hg and diastolic BP < 95 mm hg ) . after the completion of the syst-eur trial on 14 february 1997 , 3506 consenting patients ( 93.0 % of those eligible ) were enrolled in phase 2 of the syst-eur trial . this open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine . to lower the sitting systolic bp below 150 mm hg ( target bp ) , the first-line agent nitrendipine ( 10–40 mg/day ) may be associated with enalapril ( 5–20 mg/day ) , hydrochlorothiazide ( 12.5–25 mg/day ) , both add-on study drugs , or if required any other antihypertensive agent . on 1 november 1998 , 3248 patients were still being followed , 86 patients had proceeded to non-supervised follow-up , and 43 had died . the median follow-up in syst-eur 2 was 14.3 months . at the last available visit , systolic/diastolic bp in the patients formerly r and omised to placebo ( n = 1682 ) or active treatment ( n = 1824 ) , had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg , respectively , so that the between-group BP difference was 1.7 mm Hg systolic ( 95 % Cl : 0.8 to 2.6 mm Hg ; P < 0.001 ) and 0.9 mm hg diastolic ( 95 % cl : 0.4 to 1.5 mm mm hg ; P < 0.001 ) . at the beginning of syst-eur 2 , the goal bp was reached by 25.4 % and 50.6 % of the former placebo and active-treatment groups ; at the last visit these proportions were 55.9 % and 63.1 % , respectively . at that moment , 45.9 % of the patients were on monotherapy with nitrendipine , 29.3 % took nitrendipine in combination with other study drugs . until the end of 2001 , bp control of the syst-eur 2 patients will be further improved . cardiovascular complications and adverse events , such as cancer or gastro-intestinal bleeding , will be monitored and vali date d by blinded experts BACKGROUND After the double-blind , placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial ended in February 1997 , r and omized patients were offered active study medication for a further period of observation . OBJECTIVE To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia . METHODS Eligible patients had no dementia and were at least 60 years old . Their systolic blood pressure at entry was 160 to 219 mm Hg , with diastolic blood pressure below 95 mm Hg .  Antihypertensive therapy was started immediately after r and omization in the active treatment group , but only after termination of the double-blind trial in the control patients . Treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) , hydrochlorothiazide ( 12.5 - 25 mg/d ) , or both add-on drugs . RESULTS Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall . The incidence of dementia doubled from 32 to 64 cases , 41 of whom had Alzheimer disease . Throughout follow-up , systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects r and omized to active treatment . At the last examination , the blood pressure difference was still 4.2/2.9 mm Hg ; 48.1 % , 26.4 % , and 11.4 % of the control patients were taking nitrendipine , enalapril , and /or hydrochlorothiazide , whereas in the active treatment group these proportions were 70.2 % , 35.4 % , and 18.4 % , respectively . Compared with the controls , long-term antihypertensive therapy reduced the risk of dementia by 55 % , from 7.4 to 3.3 cases per 1000 patient-years ( 43 vs 21 cases , P<.001 ) . After adjustment for sex , age , education , and entry blood pressure , the relative hazard rate associated with the use of nitrendipine was 0.38 ( 95 % confidence interval , 0.23 - 0.64 ; P<.001 ) . Treatment of 1000 patients for 5 years can prevent 20 cases of dementia ( 95 % confidence interval , 7 - 33 ) . CONCLUSION The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated BACKGROUND Little information has been published on the impact of antihypertensive medications on quality of life in older persons . Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition , mood , or leisure activities . METHODS A multicenter double-blind r and omized controlled trial was conducted over an average of 5 years ' followup involving 16 academic clinical trial clinics . Participants consisted of 4736 persons ( 1.06 % ) selected from 447,921 screenees aged 60 years and older . Systolic blood pressure at baseline ranged from 160 to 219 mm Hg , while diastolic blood pressure was less than 90 mm Hg . Participants were r and omized to active antihypertensive drug therapy  or matching placebo . Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1 , while step 2 consisted of 25 to 50 mg of atenolol . If atenolol was contraindicated , 0.05 to 0.10 mg of reserpine could be used for the second-step drug . The impact of drug treatment on measures of cognitive , emotional , and physical function and leisure activities was assessed . RESULTS Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and , for some measures , a slight positive effect on cognitive , physical , and leisure function . The positive findings in favor of the treatment group were small . There was no effect on measures related to emotional state . Measures of cognitive and emotional function were stable in both groups for the duration of the study . Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period . CONCLUSIONS The overall study cohort exhibited decline over time in activities of daily living , particularly the more strenuous ones , and some decline in certain leisure activities . However , mood , cognitive function , basic self-care , and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study . Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition , emotional state , physical function , or leisure activities BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure < or = 90 mm Hg , 6264 to < or = 85 mm Hg , and 6262 to < or = 80 mm Hg . Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned  placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the < or = 90 mm Hg , < or = 85 mm Hg , and < or = 80 mm Hg target groups , respectively . The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe .  In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group < or = 80 mm Hg compared with target group < or = 90 mm Hg ( p for trend=0.005 ) . Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p<0.001 ) . INTERPRETATION Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common 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 ABSTRACT BACKGROUND There are few rigorous studies to confirm or refute the commonly cited concern that control of blood pressure to lower thresholds may result in an increased risk of falls and fractures . OBJECTIVE To compare falls and fractures in participants with type 2 diabetes in the intensive ( targeting a systolic blood pressure of < 120 mmHg ) and st and ard ( targeting a systolic blood pressure of < 140 mmHg ) blood pressure control arms of the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) r and omized trial ( N = 4,733 ) . PARTICIPANTS A subset of 3,099 participants self-reported annually on the occurrence of falls and non-spine fractures . Fractures were central ly adjudicated . MAIN MEASURES The incidence of falls in the two treatment groups was compared using a r and om-effects negative binomial model , and fracture risk was compared using Cox proportional hazards models . KEY RESULTS At enrollment in both groups , the mean age was 62 years , 44 % were women , 25 % were Black , and mean blood pressure was 138/75 mmHg . During follow-up , all classes of medications , particularly thiazide diuretics , were more commonly prescribed in the intensive group . After 1 year of follow-up , the mean systolic blood pressure was 133 ± 15 mmHg in the st and ard group and 119 ± 14 mmHg in the intensive group . The adjusted rate of falls did not differ in the intensive and st and ard groups ( 62.2/100 person-years vs. 74.1/100 person-years , RR = 0.84 , 95 % CI 0.54–1.29 , p = 0.43 ) . The risk of non-spine fractures was nonsignificantly lower in the intensive than in the st and ard blood pressure group ( HR 0.79 , 95 % CI 0.62–1.01 , p = 0.06 ) . CONCLUSIONS We conclude that intensive antihypertensive treatment that lowered mean systolic blood pressure to below 120 mmHg was not associated with an increased risk of falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes 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 The benefits of lowering a systolic blood pressure below 140 mmHg in elderly hypertension remain controversial . This study is a prospect i ve , r and omized , open-label study with blinded assessment of endpoints to compare the 2-year effect of strict treatment to maintain systolic blood pressure below 140 mmHg with that of mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg in elderly hypertensive patients . Patients with essential hypertension ( 65–85 years old , with a pretreatment systolic blood pressure of above 160 mmHg ) were r and omly assigned to receive strict treatment ( n=2,212 ) or mild treatment ( n=2,206 ) . The baseline drug was efonidipine hydrochloride , a long-acting calcium antagonist . The primary endpoint was the combined incidence of cardiovascular disease and renal failure , and the secondary endpoints were total deaths and any safety problems . Although final blood pressures ( systolic/diastolic ) were significantly lower in the strict-treatment group compared with the mild-treatment group ( 135.9/74.8 vs. 145.6/78.1 mmHg ; p<0.001 ) , the incidence of the primary endpoint was similar in the two groups ( 86 patients in each group ; p=0.99 ) . Total deaths were 54 in the strict-treatment group vs. 42 in the mild-treatment group ( p=0.22 ) , and treatment was withdrawn because of adverse events in 36 patients in each group ( p=0.99 ) . An interaction between age and treatment for the primary endpoints ( p=0.03 ) was seen . Complex clinical features associated with aging seem to have obscured the difference in effect between the two treatments . Further studies are needed to assess the optimal treatment strategy for hypertension in the elderly Background In the outcome trials that provided information on renal function in older hypertensive patients , diuretics and β-blockers were mostly used as first-line drugs . The long-term renal effects of calcium-channel blockers remain unclear . Objective To compare the changes in renal function in 2258 treated and 2148 untreated patients with isolated systolic hypertension , of whom 455 had diabetes mellitus and 390 had proteinuria . Methods We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial . Active treatment was initiated with nitrendipine ( 10–40 mg/day ) with the possible addition of enalapril ( 5–20 mg/day ) , hydrochlorothiazide ( 12.5–25 mg/day ) , or both , titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg , to less than 150 mmHg . The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault . Results Serum creatinine concentration at the time when participants were r and omly allocated to study groups was less than 176.8 μmol/l ( 2.0 mg/dl ) , averaging 88 μmol/l . At the time of the last serum creatinine measurement , the blood pressure difference ( P < 0.001 ) between the two groups was 11.6/4.1 mmHg . In the intention-to-treat analysis ( 11 427 patient – years ) , serum creatinine and the calculated creatinine clearance were not influenced by active treatment . However , in the patients assigned r and omly to receive active treatment , the incidence of mild renal dysfunction ( serum creatinine at least 176.8 mmol/l ) decreased by 64 % ( P = 0.04 ) and that of proteinuria by 33 % ( P = 0.03 ) . Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients : by 71 % , compared with 20 % ( P = 0 . 04 ) . In non-proteinuric patients , active treatment did not influence serum creatinine , whereas in patients with proteinuria at entry to the study , serum creatinine decreased on active treatment ( P < 0 . 001 ) . Furthermore , in on-r and omized treatment comparison stratified for risk at baseline , serum creatinine concentration did not change ( P = 0.98 ) in patients continuing to receive monotherapy with nitrendipine , whereas it increased by 6.73 mmol/l ( P < 0.001 ) in patients who received hydrochlorothiazide alone or in combination with other study medication ( P < 0.001 for difference in trends ) . Conclusions In older patients with isolated systolic hypertension , antihypertensive treatment starting with the dihydropyridine calcium-channel blocker , nitrendipine , did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria , especially in diabetic patients The objective of this study was to determine the relationship between prescribed daily dose frequency and  patient medication compliance .  The medication compliance of 105 patients receiving antihypertensive medications  was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal . Inaccurate compliance estimates derived using the simple pill count method were thereby avoided . Compliance was defined as the percent of days during which the prescribed number of doses were removed . Compliance improved from 59.0 % on a three-time daily regimen to 83.6 % on a once-daily regimen . Thus , compliance improves dramatically as prescribed dose frequency decreases . Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency BACKGROUND fractures may have serious implication s in an elderly individual , and fracture prevention may include a careful choice of medications . DESIGN the Hypertension in the Very Elderly Trial ( HYVET ) was a double-blind placebo-controlled trial of a thiazide-like diuretic ( indapamide 1.5 mg SR ) with the optional addition of the angiotensin-converting enzyme ( ACE ) inhibitor ( perindopril 2 - 4 mg ) . Fracture was a secondary end point of the trial . SETTING HYVET recruited participants from Eastern and Western Europe , China , Australasia , and Tunisia . SUBJECTS all participants were > or = 80 years of age and hypertensive . METHODS participants were r and omised to receive a thiazide-like diuretic ( indapamide 1.5 mg SR ) + /- ACE inhibitor ( perindopril 2 - 4 mg ) or matching placebos .  Incident fractures were vali date d and analysed based on time to first fracture . RESULTS there were 3,845 participants in HYVET and a total 102 reported fractures  ( 42 in the active and 60 in the placebo group ) . When taking only vali date d first fractures , 90 were included in the analyses ( 38 in the active and 52 in the placebo group ) . Cox proportional hazard regression , adjusted for key baseline risk factors , result ed in a point estimate of 0.58 ( 95 % CI 0.33 - 1.00 , P = 0.0498 ) . CONCLUSIONS despite the lowering of blood pressure , treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate OBJECTIVE --To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke , coronary heart disease , and death . DESIGN --R and omised , placebo controlled , single blind trial . SETTING --226 general practice s in the MRC general practice research framework . SUBJECTS--4396 patients aged 65 - 74 r and omised to receive diuretic , beta blocker , or placebo . Patients had mean systolic pressures of 160 - 209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment . INTERVENTION-- Patients were r and omised to atenolol 50 mg daily ; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily ; or placebo . The regimens were adjusted to achieve specified target pressures . Mean follow up was 5.8 years . MAIN OUTCOME MEASURES --Strokes , coronary events , and deaths from all causes . RESULTS --Both treatments reduced blood pressure below the level in the placebo group . Compared with the placebo group , actively treated subjects ( diuretic and beta blocker groups combined ) had a 25 % ( 95 % confidence interval 3 % to 42 % ) reduction in stroke ( p = 0.04 ) , 19 % ( -2 % to 36 % ) reduction in coronary events ( p = 0.08 ) , and 17 % ( 2 % to 29 % ) reduction in all cardiovascular events ( p = 0.03 ) . After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke ( 31 % ( 3 % to 51 % ) p = 0.04 ) , coronary events ( 44 % ( 21 % to 60 % ) , p = 0.0009 ) , and all cardiovascular events ( 35 % ( 17 % to 49 % ) , p = 0.0005 ) compared with the placebo group . The beta blocker group showed no significant reductions in these end points . The reduction in strokes was mainly in non-smokers taking the diuretic . CONCLUSION --Hydrochlorothiazide and amiloride reduce the risk of stroke , coronary events , and all cardiovascular events in older hypertensive adults Objectives To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients . Design The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre , prospect i ve , double-blind , parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria r and omized to at least 2-year VeraTran ( verapamil/tr and olapril 180 mg/2 mg daily ) or tr and olapril ( 2 mg daily , identical image ) treatment . Main outcome was persistent macroalbuminuria ( albuminuria > 200 μg/min in two consecutive visits ) . Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7 % . Results Over a median follow-up of 4.5 years , 18 patients ( 13 % ) on VeraTran vs. 15 ( 10.5 % ) on tr and olapril [ unadjusted hazard ratio ( 95 % confidence interval [ CI ] ) 1.07 ( 0.54–2.12 ) , P = 0.852 ] progressed to macroalbuminuria , respectively ; 62 ( 44.9 % ) vs. 71 ( 49.7 % ) [ 0.80 ( 0.57–1.12 ) , P = 0.198 ] regressed to normoalbuminuria ( urinary albumin excretion < 20 μg/min ) , and 20 ( 14.5 % ) vs. 21 ( 14.7 % ) [ hazard ratio 0.93 ( 0.50–1.72 ) , P = 0.816 ] had major cardiovascular events . BP and metabolic control were similar between groups . Patients with cardiovascular events were significantly less [ 13 ( 9.8 % ) vs. 28 ( 18.9 % ) , hazard ratio : 0.37 ( 0.19–0.71 ) , P = 0.003 ] among those regressing to normoalbuminuria than those without regression . Difference was independent of treatment allocation and was significant also after adjusting for baseline characteristics [ 0.40 ( 0.20–0.79 ) , P = 0.009 ] , follow-up SBP [ 0.40 ( 0.20–0.80 ) , P = 0.010 ] or DBP [ 0.36 ( 0.18–0.73 ) , P = 0.004 ] BP or HbA1C [ 0.43 ( 0.21–0.88 ) , P = 0.021 ] . Conclusion In hypertensive type 2 diabetes patients with microalbuminuria , verapamil added-on tr and olapril did not improve renal or cardiovascular outcomes . Independent of verapamil , tr and olapril normalized albuminuria in half of patients and this translated into significant cardioprotection BACKGROUND The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown . We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients . METHODS In this r and omised open-label trial undertaken in 44 centres in Italy , 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were r and omly assigned to a target systolic blood pressure of less than 140 mm Hg ( usual control ; n=553 ) or less than 130 mm Hg ( tight control ; n=558 ) . After stratification by centre , we used a computerised r and om function to allocate patients to either group . Observers who were unaware of r and omisation read electrocardiograms and adjudicated events . Open-label agents were used to reach the r and omised targets . The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after r and omisation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00421863 . RESULTS Over a median follow-up of 2.0 years ( IQR 1.93 - 2.03 ) , systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg ( SD 10.6/7.0 ) in the usual-control group and by 27.3/10.4 mm Hg ( 11.0/7.5 ) in the tight-control group ( between-group difference 3.8 mm Hg systolic [ 95 % CI 2.4 - 5.2 ] , p<0.0001 ; and 1.5 mm Hg diastolic [ 0.6 - 2.4 ] ; p=0.041 ) . The primary endpoint occurred in 82 of 483 patients ( 17.0 % ) in the usual-control group and in 55 of 484 patients ( 11.4 % ) of the tight-control group ( odds ratio 0.63 ; 95 % CI 0.43 - 0.91 ; p=0.013 ) . A composite cardiovascular endpoint occurred in 52 ( 9.4 % ) patients in the usual-control group and in 27 ( 4.8 % ) in the tight-control group ( hazard ratio 0.50 , 95 % CI 0.31 - 0.79 ; p=0.003 ) . Side-effects were rare and did not differ significantly between the two groups . INTERPRETATION Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension . FUNDING Boehringer-Ingelheim , Sanofi-Aventis , Pfizer 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 . IMPORTANCE Persons with type 2 diabetes mellitus ( T2DM ) are at increased risk for decline in cognitive function , reduced brain volume , and increased white matter lesions in the brain . Poor control of blood pressure ( BP ) and lipid levels are risk factors for T2DM-related cognitive decline , but the effect of intensive treatment on brain function and structure is unknown . OBJECTIVE To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume ( TBV ) in patients with T2DM . DESIGN , SETTING , AND PARTICIPANTS A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c ( HbA1c ) levels less than 7.5 % r and omized to a systolic BP goal of less than 120 vs less than 140 mm Hg ( n = 1439 ) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL ( n = 1538 ) . Participants were recruited from August 1 , 2003 , through October 31 , 2005 , with the final follow-up visit by June 30 , 2009 . MAIN OUTCOME MEASURES Cognition was assessed at baseline and 20 and 40 months . A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health . RESULTS Baseline mean HbA1c level was 8.3 % ; mean age , 62 years ; and mean duration of T2DM , 10 years . At 40 months , no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial . At 40 months , TBV had declined more in the intensive vs st and ard BP-lowering group ( difference , -4.4 [ 95 % CI , -7.8 to -1.1 ] cm(3 ) ; P = .01 ) . Fibrate therapy had no effect on TBV compared with placebo . CONCLUSIONS AND RELEVANCE In participants with long-st and ing T2DM and at high risk for cardiovascular events , intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up . Intensive BP control was associated with greater decline in TBV at 40 months relative to st and ard therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000620 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 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 Background — The effect of intensive blood pressure ( BP ) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate ( eGFR ) is not established . Methods and Results — Among 2610 participants r and omized to a lower ( < 130 mm Hg ) versus higher ( 130–149 mm Hg ) systolic BP target with repeated measures of serum creatinine , we evaluated differences by study arm in annualized eGFR decline and rapid decline ( eGFR decline > 30 % ) using linear mixed models and logistic regression , respectively . We assessed associations of both treatment and kidney function decline with stroke , major vascular events , and the composite of stroke , death , major vascular events , or myocardial infa rct ion using multivariable Cox regression , separately and jointly including a test for interaction . Analyses were conducted by treatment arm . Mean age was 63±11 years ; 949 participants ( 36 % ) were diabetic ; and mean eGFR was 80±19 mL·min−1·1.73 m−2 . At 9 months , achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group , and differences were maintained throughout follow-up ( mean , 3.2 years ) . Compared with the higher target , the lower BP target had a −0.50–mL·min−1·1.73 m−2 per year ( 95 % confidence interval [ CI ] , −0.79 to −0.21 ) faster eGFR decline . Differences were most pronounced during the first year ( −2.1 mL·min−1·1.73 m−2 ; 95 % CI , −0.97 to −3.2 ) , whereas rates of eGFR decline did not differ after year 1 ( −0.095 ; 95 % CI , −0.47 to 0.23 ) . A total of 313 patients ( 24 % ) in the lower BP group had rapid kidney function decline compared with 247 ( 19 % ) in the higher BP group ( odds ratio , 1.4 ; 95 % CI , 1.1–1.6 ) . Differences in rapid decline by treatment arm were apparent in the first year ( odds ratio , 1.4 ; 95 % CI , 1.1–1.8 ) but were not significant after year 1 ( odds ratio , 1.0 ; 95 % CI , 0.73–1.4 ) . Rapid decline was associated with higher risk for stroke , major vascular events , and composite after full adjustment among individuals r and omized to the higher BP target ( stroke hazard ratio , 1.93 ; 95 % CI , 1.15–3.21 ) but not the lower BP arm ( stroke hazard ratio , 0.93 ; 95 % CI , 0.50–1.75 ; all P for interaction < 0.06 ) . Conclusions — In patients with prior lacunar stroke and relatively preserved kidney function , intensive BP lowering was associated with a greater likelihood of rapid kidney function decline . Differences were observed primarily during the first year of antihypertensive treatment . Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering . Clinical Trial Registration — URL : http://www . clinical Trials.gov . Unique identifier : NCT00059306 Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient IMPORTANCE The appropriate treatment target for systolic blood pressure ( SBP ) in older patients with hypertension remains uncertain . OBJECTIVE To evaluate the effects of intensive ( < 120 mm Hg ) compared with st and ard ( < 140 mm Hg ) SBP targets in persons aged 75 years or older with hypertension but without diabetes . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial ( SPRINT ) . Recruitment began on October 20 , 2010 , and follow-up ended on August 20 , 2015 . INTERVENTIONS Participants were r and omized to an SBP target of less than 120 mm Hg ( intensive treatment group , n = 1317 ) or an SBP target of less than 140 mm Hg ( st and ard treatment group , n = 1319 ) . MAIN OUTCOMES AND MEASURES The primary cardiovascular disease outcome was a composite of nonfatal myocardial infa rct ion , acute coronary syndrome not result ing in a myocardial infa rct ion , nonfatal stroke , nonfatal acute decompensated heart failure , and death from cardiovascular causes . All-cause mortality was a secondary outcome . RESULTS Among 2636 participants ( mean age , 79.9 years ; 37.9 % women ) , 2510 ( 95.2 % ) provided complete follow-up data . At a median follow-up of 3.14 years , there was a significantly lower rate of the primary composite outcome ( 102 events in the intensive treatment group vs 148 events in the st and ard treatment group ; hazard ratio [ HR ] , 0.66 [ 95 % CI , 0.51 - 0.85 ] ) and all-cause mortality ( 73 deaths vs 107 deaths , respectively ; HR , 0.67 [ 95 % CI , 0.49 - 0.91 ] ) . The overall rate of serious adverse events was not different between treatment groups ( 48.4 % in the intensive treatment group vs 48.3 % in the st and ard treatment group ; HR , 0.99 [ 95 % CI , 0.89 - 1.11 ] ) . Absolute rates of hypotension were 2.4 % in the intensive treatment group vs 1.4 % in the st and ard treatment group ( HR , 1.71 [ 95 % CI , 0.97 - 3.09 ] ) , 3.0 % vs 2.4 % , respectively , for syncope ( HR , 1.23 [ 95 % CI , 0.76 - 2.00 ] ) , 4.0 % vs 2.7 % for electrolyte abnormalities ( HR , 1.51 [ 95 % CI , 0.99 - 2.33 ] ) , 5.5 % vs 4.0 % for acute kidney injury ( HR , 1.41 [ 95 % CI , 0.98 - 2.04 ] ) , and 4.9 % vs 5.5 % for injurious falls ( HR , 0.91 [ 95 % CI , 0.65 - 1.29 ] ) . CONCLUSIONS AND RELEVANCE Among ambulatory adults aged 75 years or older , treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg result ed in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01206062
target: Benefits of Treating Higher Versus Lower BP Targets in Older Adults Across all trials , treating high BP in older adults was beneficial .
  This is probably related to the higher frequency of cardiovascular events seen in these patients .
  Treatment Effects According to Diastolic BP Evidence was insufficient to determine the benefit of treating diastolic hypertension in the absence of systolic hypertension .
  A subgroup analysis of SPRINT showed a nonstatistically significant increase in the rate of serious adverse events , hypotension , syncope , electrolyte abnormalities , or acute
background: Hypertension , an elevation of systemic arterial blood pressure ( BP ) , is a very common chronic disease in the United States .
  The overall prevalence of hypertension among U.S. adults is 29.0 % , and it increases to 64.9 % in adults aged 60 years or older ( 1 ) .
  Hypertension was associated with a total of $ 46 billion in health care services , medications , and missed days of work in the United States in 2011 ( 2 ) .
  Appropriate management of hypertension reduces the risk for cardiovascular disease , renal disease , cerebrovascular disease , and death ( 36 ) .
  However , determining the most appropriate BP targets , particularly for adults aged 60 years or older , has been controversial .
  Debate about the goal for systolic BP ( SBP ) among adults treated for hypertension has intensified , especially in light of recent recommendations ( 7 ) .
  In addition , when selecting BP targets for adults aged 60 years or older , clinicians need to consider comorbid conditions that could affect treatment choice .
  Original Version ( PDF ) Guideline Focus and Target Population The purpose of this American College of Physicians ( ACP ) and American Academy of Family Physicians ( AAFP ) joint guideline is to present evidence -based recommendations on the benefits and harms of higher ( < 150 mm Hg ) versus lower ( 140 mm Hg ) SBP targets for the treatment of hypertension in adults aged 60 years or older .
  These recommendations are based on a background evidence review ( 8) and systematic review sponsored by the U.S. Department of Veterans Affairs ( VA ) ( 9 ) .