Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Detection and treatment of hypertension in older individuals. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 mm Hg in Patients Aged 60 Years or Older: The Minority View Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial Blood pressure and isolated systolic hypertension and the risk of coronary heart disease and mortality in elderly men (the Zutphen Elderly Study) Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group. Implications of the Systolic Hypertension in the Elderly Program: The Systolic Hypertension in the Elderly Program Cooperative Research Group Effect of age on blood pressure parameters and risk of cardiovascular death in men. The systolic hypertension in the elderly pilot program: methodological issues. Isolated systolic hypertension: data from the European Working Party on High Blood Pressure in the Elderly. Syst‐Eur—A Multicenter Trial on the Treatment of Isolated Systolic Hypertension in the Elderly: First Interim Report The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): Protocol, Patient Characteristics, and Blood Pressure during the First 12 Months Practitioner's trial on the efficacy of antihypertensive treatment in elderly patients with hypertension II (PATE-hypertension II study) in Japan. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. [SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].
BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients The Hypertension Detection and Follow-up Program screened 34,012 individuals aged 60 - 69 years old in their homes in 14 communities around the United States during 1972 and 1973 . The prevalence of hypertension , defined as diastolic blood pressure greater than or equal to 90 mmHg or on antihypertensive medication , was 42.1 % . After a second clinic screen , 2,376 hypertensives were identified and r and omized into Stepped Care , a special intensive treatment group , or Referred Care , a group referred to their usual medical care sources . These individuals were followed for five years ( until they reached the ages of 65 - 74 years ) . Over the five years , 79.4 % of older individuals remained under active care and 81.4 % of those were at their goal diastolic blood pressure . Side-effects tended to be less frequent in older individuals than in younger ones . Older Stepped Care participants with mild hypertension ( diastolic blood pressure 90 - 104 mmHg ) had a 17.2 % reduction in all-cause mortality over five years compared to Referred Care , which was primarily due to a reduction in deaths attributed to cardiovascular causes . Thus , antihypertensive treatment can be safely and beneficially administered to individuals in this age range with diastolic hypertension , including those with mild hypertension BACKGROUND Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70-<80 , n=6126 ; 60-<70 , n=7602 ; < 60 , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P < .001 ) . Treatment decreased systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension ( ISH ) [ systolic blood pressure ( SBP ) greater than or equal to 160 mmHg , diastolic blood pressure ( DBP ) less than 90 mmHg ] reduces the 5 year incidence of fatal and nonfatal stroke . Between March 1 , 1985 and January 15 , 1988 , 4736 persons ( target 4800 ) with ISH , age 60 years and over , were enrolled . Potential participants met blood pressure ( BP ) and age criteria . Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued , and then met BP criteria ( 33 % of cohort ) . Stepped-care therapy with chlorthalidone and atenolol ( alternative , reserpine ) or matching placebos was initiated as first and second steps . At baseline the trial population was 43.1 % male , 56.9 % female ; 13.9 % black , 86.1 % non-black . Also , the mean age was 71.6 years ; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg ; 59.8 % had codeable resting electrocardiographic abnormalities .  The trial is now in follow-up phase with scheduled termination in 1991 The 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) recommends several major changes from the JNC 7 report ( 1 , 2 ) . The 2014 guideline is based on a systematic review of r and omized , controlled trials ( RCTs ) by a multidisciplinary panel using a process informed by Institute of Medicine recommendations for guideline development ( 3 ) . Although there was almost unanimous agreement on nearly all recommendations , a minority of the panel ( the authors of this commentary ) disagreed with the recommendation to increase the target systolic blood pressure ( SBP ) from 140 to 150 mm Hg in persons aged 60 years or older without diabetes mellitus ( DM ) or chronic kidney disease ( CKD ) . This target guides both the initiation of therapy and treatment goals . Although this issue has major clinical and public health implication s , the guideline only briefly summarized the concerns underlying the minority opinion to maintain the target of less than 140 mm Hg . The Institute of Medicine recommendation for guideline development encourages guidelines to provide a description and explanation of any differences of opinion regarding the recommendation ( 3 ) . This summarizes the evidence and rationale underlying the minority opinion to maintain the SBP target of 140 mm Hg or lower in persons aged 60 years or older until there is greater certainty of the risks and benefits of a higher target . First , increasing the target will probably reduce the intensity of antihypertensive treatment in a large population at high risk for cardiovascular disease ( CVD ) ( Table 1 ) . The higher SBP goal would apply to some of the groups at highest cardiovascular risk , such as African Americans , hypertensive patients with multiple CVD risk factors other than DM or CKD , and those with clinical CVD . Second , the evidence supporting increasing the SBP target from 140 to 150 mm Hg in persons aged 60 years or older was insufficient and inconsistent with the evidence supporting the panel 's recommendations for an SBP target of less than 140 mm Hg in persons younger than 60 years and those aged 60 years or older with DM or CKD . Third , the higher SBP goal in individuals aged 60 years or older may reverse the decades-long decline in CVD , especially stroke mortality ( 4 ) . In the absence of definitive evidence defining the optimum SBP target , observational studies and RCT data that the panel did not systematic ally review more strongly support the SBP goal of less than 140 mm Hg , especially in high-risk individuals . Other recent guideline groups review ing similar evidence have recommended a goal of less than 140 mm Hg , particularly in persons aged 80 years or younger ( 59 ) . Table 1 . U.S. Cardiovascular Disease Death Rates for Persons Younger and Older Than 65 y Persons Aged 60 Years or Older With Hypertension and SBP Controlled to 140 mm Hg or Lower More than half of the 72 million persons with hypertension in the United States are aged 60 years or older ( 10 , 11 ) . Among these individuals , the 2014 guideline recommends the SBP goal of 140 mm Hg or lower only for those with DM and those younger than 70 years with CKD ( 2 ) . Although the prevalence of hypertension in this age group ( 65 % to 67 % ) did not change between 1999 and 2010 , the percentage with adequate blood pressure control increased from 27.4 % ( 19992000 ) to 50.5 % ( 20112012 ) , with 82.2 % now receiving antihypertensive medications ( 10 , 12 ) . Data from NHANES ( National Health and Nutrition Examination Survey ) from 2001 to 2008 show that among treated and untreated hypertensive adults aged 60 years or older , median SBPs were 136 mm Hg and 152 mm Hg , respectively ( 13 ) , and SBPs have been decreasing in this age group over the past 5 decades ( Figure ) ( 4 ) . Thus , a target of less than 150 mm Hg would likely increase blood pressures in the treated hypertensive population and would suggest that nearly half of the untreated hypertensive patients in this age range should remain untreated . The large population at high risk for CVD , with most currently at an SBP of 140 mm Hg or lower , creates concern that a higher SBP target will adversely affect public health . Figure . Smoothed weighted frequency distribution , median , and 90th percentile of systolic blood pressure for persons aged 60 to 74 y : United States , 19592010 . Reproduced from Lackl and and colleagues ( 4 ) . NHANES = National Health and Nutrition Examination Survey ; NHES = National Health Examination Survey . High Risk in Persons With the Higher Goal Age substantially increases risk for cardiovascular events ( Table 1 ) , so differences in cardiovascular risk do not justify different targets for patients older and younger than 60 years . The risk range for white and African American men aged 60 years is 9 % to 30 % , depending on risk factor profile . For men of both ethnicities who are aged 70 years or older and have SBP controlled to 140 mm Hg , even without clinical CVD or DM , the 10-year risk exceeds 20 % ( 14 ) . Thus , on the basis of absolute risk , using an age threshold of 60 years to define eligibility for less aggressive treatment lacks consistency . Persons aged 60 to 79 years are at higher risk than those who are younger , even if the younger persons have DM . Insufficient Evidence for Differential Hypertension Treatment Benefit for Patients Older and Younger Than 60 Years The 2014 guideline panel failed to identify evidence of differential benefits or harms of treatment using an SBP goal of 140 mm Hg with an age threshold of 60 years . There is little RCT evidence of risk or benefit in treating persons younger than 60 years to this target , except in those with diastolic hypertension . The guideline indicates that no qualifying evidence was found comparing an SBP less than 140 mm Hg to any other SBP goal for persons younger than 60 years ( 2 ) . However , in persons aged 60 years or older , the SHEP ( Systolic Hypertension in the Elderly Program ) trial showed benefit of treating hypertension to an SBP goal between 140 and 145 mm Hg ( Table 2 ) ( 15 ) . HYVET ( Hypertension in the Very Elderly Trial ) found a benefit of an SBP target of less than 150 mm Hg on health outcomes , including mortality in persons aged 80 years or older ( 16 ) . Patients in the HYVET treatment group achieved an SBP of 144 mm Hg at 2 years compared with 159 mm Hg in the control group , and blood pressures continued to decrease in both groups until the end of the trial . Therefore , HYVET and the SHEP trial provide evidence that reducing SBP to around 140 mm Hg has substantial benefit without major harm in older persons . Thus , the best evidence available for an SBP target around 140 mm Hg , which meets the guideline RCT criteria , is in persons older than 60 years . The lack of benefit seen in 2 Japanese trials in older individuals ( JATOS [ Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients ] [ 17 ] and the VALISH [ Valsartan in Elderly Isolated Systolic Hypertension ] trial [ 18 ] ) was cited by some to rationalize the higher SBP target , but these trials were underpowered ( Table 2 ) . The SHEP trial and HYVET together reported 365 strokes and more than 285 coronary heart disease events , whereas JATOS and the VALISH trial only had a combined total of 125 strokes and 67 coronary heart disease events . In addition , the much larger FEVER ( Felodipine Event Reduction ) trial ( 19 ) did not meet criteria for inclusion in the panel 's deliberation ( Table 2 ) . This trial , which was conducted in a Chinese population ( age range , 50 to 79 years ; mean age , 62 years ) , reported a significant 27 % reduction in its primary outcome , as well as significant reductions in all CVD , total mortality , coronary heart disease , and heart failure in patients treated to an SBP of 137 mm Hg with a thiazide diureticcalcium-channel blocker combination versus 143 mm Hg with a thiazide diuretic plus placebo ( 19 ) . Table 2 . Trials Comparing Different Systolic Blood Pressure Thresholds In addition , generalizability of the Japanese trials to other population s of patients older than 60 years , such as African Americans , is uncertain . African Americans are at highest risk for all complications of hypertension and are historically undertreated . Thus , we believe that recommending less aggressive targets in this or other high-risk population s requires stronger justification than the guideline cites . Three recent guidelines from other countries have concluded that the appropriate cut point for an age-related differential SBP goal is 80 years or older ( 57 ) . We agree that this higher treatment target in frail hypertensive patients aged 80 years or older better reflects existing evidence . Safety and Adverse Event Risk in Hypertensive Patients Aged 60 Years or Older Despite the limited number of end points in JATOS and the VALISH trial , their size and duration provide evidence of safety of the SBP target of less than 140 mm Hg . The VALISH investigators concluded that this target was safe in relatively healthy patients aged 70 years or older with isolated systolic hypertension ( 18 ) . In JATOS , adverse events requiring treatment discontinuation were reported in only 36 patients , with no differences in discontinuation rate between groups ( 17 ) . This evidence and the favorable results at slightly higher blood pressures in the SHEP trial and HYVET provide reassurance of the safety of an SBP goal of less than 140 mm Hg in older , nonfrail persons . Other Trial Evidence of Benefit of Treatment at an SBP of 140 mm Hg or Lower Results of the SPS3 ( Secondary Prevention of Small Subcortical Strokes ) trial indicated that an SBP target of less than 130 mm Hg versus 144 mm Hg in 3020 patients ( mean age , 63 years ) reduced subsequent strokes by 19 % ( P= 0.08 ) and hemorrhagic strokes by nearly 50 % ( P < 0.01 ) ( 20 ) . Of note , the FEVER trial reported a 44 % ( P < 0.001 ) reduction in all strokes in a subgroup analysis of patients older than 65 years ( 17 ) . Finally , 2 meta-analyses Background To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension  , we extended the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial by an open-label follow-up study lasting 4 years . Methods The Syst-Eur trial included 4695 r and omized patients with minimum age of 60 years and an untreated blood pressure of 160–219 mmHg systolic and below 95 mmHg diastolic . The double-blind trial ended after a median follow-up of 2.0 years ( range 1–97 months ) . Of 4409 patients still alive , 3517 received open-label treatment consisting of nitrendipine ( 10–40 mg daily ) with the possible addition of enalapril ( 5–20 mg daily ) , hydrochlorothiazide ( 12.5–25 mg daily ) , or both add-on drugs .  Non- participants ( n = 892 ) were also followed up . Results Median follow-up increased to 6.1 years . Systolic pressure decreased to below 150 mmHg ( target level ) in 2628 participants ( 75.0 % ) . During the 4-year open-label follow-up , stroke and cardiovascular complications occurred at similar frequencies in patients formerly r and omized to placebo and those continuing active treatment . These rates were similar to those previously observed in the active-treatment group during the double-blind trial . Considering the total follow-up of 4695 r and omized patients , immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28 % ( P = 0.01 ) and 15 % ( P = 0.03 ) , respectively , with a similar tendency for total mortality ( 13 % , P = 0.09 ) . In 492 diabetic patients , the corresponding estimates of long-term benefit ( P < 0.02 ) were 60 , 51 and 38 % , respectively . Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension . Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years . These findings underscore the necessity of early treatment of isolated systolic hypertension Objective To investigate the associations of diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) with the risk of coronary heart disease , sudden cardiac and all-cause death in elderly men . Design A cohort study . Setting The Dutch town of Zutphen . Subjects Eight hundred and eighty-five r and omly selected men , aged 64 - 84 years . Main outcome measures Relative risks adjusted for age , body mass index , total and high-density lipoprotein cholesterol , cigarette smoking , alcohol consumption , use of blood pressure-lowering medications without a specific indication for hypertension , and the physician who measured the blood pressure . Results Neither DBP nor SBP was associated significantly with the incidence of a first coronary heart disease event and no clear associations were observed with mortality from coronary heart disease . However , positive associations with sudden cardiac death were observed . The adjusted relative risk for men with definite isolated systolic hypertension was 9.20 . The risk of dying from coronary heart disease not recorded additionally as sudden death was highest in men at the lower end of the DBP and SBP distributions and in men using antihypertensives . DBP and SBP were positively associated with all-cause mortality when possible comorbidity at the time of the blood pressure measurement was accounted for . Overall , the highest risk for all endpoints was observed in men on antihypertensive medication , who formed a distinct group with a clustering of cardiovascular risk factors . Conclusion Elevated DBP and SBP , and especially isolated systolic hypertension , are important predictors of sudden cardiac death in elderly men . The highest risk of nonsudden coronary heart disease mortality was found at the lower end of the blood pressure distributions and among men on antihypertensive medication 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 & NA ; Several imperatives drive the need to establish the merit of treating isolated systolic hypertension in the elderly . These include its higher prevalence with age , the associated excess cardiovascular risks , and the rapid aging of the population . The Systolic Hypertension in the Elderly Program demonstrated a significant reduction in stroke incidence ( fatal and nonfatal ) ( 36 % , equivalent to preventing 30 strokes per 1,000 participants per 5 years ) . A 27 % reduction in coronary heart disease incidence and a 32 % reduction in all major cardiovascular events were also achieved ( equivalent to the prevention of 16 and 55 events per 1,000 participants per 5 years , respectively ) . These results were associated with a treatment regimen in which the primary agent was low‐dose chlorthalidone . The benefits accrued to all subgroups identified based on baseline age , race and sex , blood pressure , serum cholesterol levels , and electrocardiographic abnormalities . The reduction in coronary disease is consistent with predictions based on prospect i ve epidemiological studies and is concordant with other recent intervention trials . It is a reasonable inference from the Systolic Hypertension in the Elderly Program findings that middle‐aged as well as older people with isolated systolic hypertension , and people with less severe degrees of this condition , particularly when other risk factors are present , would benefit from such therapy . Another reasonable implication of the trial relates to the matter of preferred drug treatment regimens for diastolic hypertension , in middle‐aged as well as older people . A low‐dose diuretic regimen is clearly the initial treatment of choice for most hypertensive patients , based on demonstrated reduction in risk for major cardiovascular events , including coronary heart disease , and its safety , patient acceptance , and low cost . ( Hypertension 1993;21:335‐343 BACKGROUND Elevated blood pressure ( BP ) is a risk factor for cardiovascular disease ( CVD ) , but it remains unclear which component-alone or in combination-is the best predictor . We sought to determine which BP parameters are important predictors of CVD death across a wide age range . METHODS We used a prospect i ve cohort study design with 53,163 men followed for cause-specific death during a median of 5.7 years in the Physicians ' Health Study enrollment cohort . Baseline age , systolic BP and diastolic BP were collected . We calculated relative risks ( RRs ) and their 95 % confidence intervals using Cox proportional hazard models adjusting for major risk factors for CVD , and then stratified by age ( 39 to 49 , 50 to 59 , 60 to 69 , and 70 to 84 years ) . RESULTS There were 459 CVD deaths during follow-up . For each 10 mm Hg increase in systolic BP , the multivariable RRs by ascending age group were 1.46 , 1.43 , 1.24 , and 1.13 . The multivariable RRs for each 10 mm Hg increase in diastolic BP were 1.25 , 1.20 , 1.28 , and 1.07 . Compared with systolic BP , pulse pressure and mean arterial pressure were not consistent predictors across age ranges , and combining systolic BP with another parameter did not improve the model compared with using systolic BP alone in any age group ( all P > .05 ) . CONCLUSIONS In this large cohort of healthy men with no history of hypertension , systolic BP was the most consistent and significant predictor of CVD death across all ages . Diastolic BP was not as strongly associated with risk . Our results support the continuing emphasis on using systolic BP in predicting cardiovascular risk The Systolic Hypertension in the Elderly Program ( SHEP ) Pilot Study was conducted to determine the feasibility of conducting a long-term placebo-controlled r and omized clinical trial in elderly subjects . Enrolled in the study were 551 men and women between the ages of 60 and 90 years with isolated systolic hypertension ( SBP greater than or equal to 160 mmHg and DBP less than 90 mmHg ) . The study showed that it is possible to recruit old and very old subjects into a clinical trial ; the elderly are good compliers ( drugs and follow-up visits ) , with some decline after the age of 80 ; control of blood pressure was accomplished in the large majority of patients ; evaluation of side effects represents a potential problem as varied complaints increase with age thus creating difficulties in distinguishing those attributed to the study drug ; and finally , cause-specific mortality is probably preferable to all-cause mortality as an end-point in prevention trials of antihypertensive regimens The European Working Party on High Blood Pressure in the Elderly study ( EWPHE ) was a placebo-controlled , double-blind , inter-patient assessment of diuretic treatment in hypertensive patients aged 60 years or more . Of the 840 patients included in the study 247 had isolated systolic hypertension ( systolic blood pressure greater than or equal to 160 and diastolic blood pressure less than or equal to 95 mmHg ) . In those ( n = 120 ) r and omized to active treatment ( diazide-hydrochlorothiazide with triamterene + /- methyldopa )  blood pressure after 3 years was , on average , 19/8 mmHg lower than in the placebo group ( n = 119 ) and after 5 years the difference was 9/7 mmHg . Data on mortality and morbidity were insufficient for firm conclusions to be drawn . The data are presented here only to communicate the trends observed and to provide information that may be useful in the design of future trials . The trends observed for cardiac mortality , terminating non-fatal events ( including severe heart failure ) and combined fatal and non-fatal cardiovascular events follow a similar pattern to that observed in the trial overall , in that active treatment appeared to confer benefit . However , in the case of isolated systolic hypertension none of these differences between active and placebo treatment achieved statistical significance . We conclude that , given the epidemiological data incriminating systolic hypertension as a risk factor and the data presented here , a rigorous assessment of the value of treating isolated systolic hypertension is justified Syst-Eur is a multicenter placebo-controlled outcome trial design ed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension ( ISH ) . Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160 - 219 mm Hg with a diastolic blood pressure less than 95 mm Hg . The present paper is an interim report on the first 316 patients r and omized into this trial . The placebo ( n = 170 ) and active treatment ( n = 146 ) groups were similar at r and omization with respect to age ( 73 + /- 8 years ; mean + /- SD ) , sitting blood pressure ( 178 + /- 12 mm Hg systolic ; 85 + /- 7 mm Hg diastolic ) , percentage of men ( 34 % ) , and percentage of patients with cardiovascular complications ( 29 % ) . After r and omization blood pressure fell more ( p less than 0.001 ) in patients on active treatment than in those in the placebo group ( 19 + /- 20 mm Hg systolic ; 6 + /- 10 mm Hg diastolic vs. 7 + /- 19 and 1 + /- 10 mm Hg for sitting blood pressure ) . This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained . New centers are being recruited in order to r and omize a total of 3,000 patients The benefits of a systolic blood pressure ( BP ) below 150–160 mmHg are well established ; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial . This study was design ed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg ( group A ) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg ( group B ) . The study design followed the Prospect i ve R and omized Open Blinded End-point ( PROBE ) study . The subjects were elderly patients ( 65–85 years old ) who consistently had a systolic BP of 160 mmHg or higher . The baseline drug was efonidipine hydrochloride ( efonidipine ) , a long-acting dihydropiridine calcium antagonist . The primary endpoints were stroke , cardiac disease , vascular disease , and renal failure . After a run-in period of 2 to 4 weeks , 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex , age , baseline BP , or other cardiovascular risk factors . The systolic BP was 7.2 mmHg lower ( p<0.0001 ) and the diastolic BP 2.4 mmHg lower ( p<0.0001 ) in group A than in group B after 12 months of treatment . As of this interim analysis , primary endpoints have occurred in 87 patients ( stroke in 58 patients , cardiac disease in 27 patients , occlusive arterial disease in 1 patient , and renal failure in 1 patient ) . Five patients have died of stroke and 2 patients of myocardial infa rct ion . The primary -endpoint-related morbidity rate was 20.9/1,000 patient-years , and the mortality rate was 1.7/1,000 patient-years . Currently available results indicate that this study , one of the largest r and omized trials of antihypertensive therapy in elderly patients in Japan , was conducted safely . The final results are expected to provide important and practical information for the management of hypertension in elderly patients AIM Reduction of elevated blood pressure ( BP ) has been an important treatment goal in elderly hypertensive patients . However , it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients . We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy , tolerability and impact on cardiovascular/cerebrovascular ( CV ) morbidity/mortality in a large cohort of Japanese patients . METHODS This study was performed at general practitioners ' offices nationwide with a target sample size of 1500 patients . Hypertensive patients aged 60years or more who achieved successful BP control with c and esartan monotherapy , and who tolerated the treatment for at least 8weeks , were enrolled into the study and followed for 3years . RESULTS BP was maintained below the target level of 140/90mmHg over the 3-year period . The incidence of CV events during the study period was 20.4/1000person-years . Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events . However , very elderly patients ( ≥75years ) with a systolic BP ( SBP ) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120 - 139mmHg . CONCLUSION This study demonstrated that treatment with c and esartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events . CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older , which suggests that excessive BP reductions might be harmful for very elderly patients CONTEXT The clinical use of ambulatory blood pressure ( BP ) monitoring requires further validation in prospect i ve outcome studies . OBJECTIVE To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension . DESIGN Sub study to the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial , started in October 1988 with follow up to February 1999 . The conventional BP at r and omization was the mean of 6 readings ( 2 measurements in the sitting position at 3 visits 1 month apart ) . The baseline ambulatory BP was recorded with a noninvasive intermittent technique . SETTING Family practice s and outpatient clinics at primary and secondary referral hospitals . PARTICIPANTS A total of 808 older ( aged > or = 60 years ) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic . INTERVENTIONS For the overall study , patients were r and omized to nitrendipine ( n = 415 ; 10 - 40 mg/d ) with the possible addition of enalapril ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25.0 mg/d ) or to matching placebos ( n = 393 ) . MAIN OUTCOME MEASURES Total and cardiovascular mortality , all cardiovascular end points , fatal and nonfatal stroke , and fatal and nonfatal cardiac end points . RESULTS After adjusting for sex , age , previous cardiovascular complications , smoking , and residence in western Europe , a 10-mm Hg higher conventional systolic BP at r and omization was not associated with a worse prognosis , whereas in the placebo group , a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate ( HR ) of most outcome measures ( eg , HR , 1.23 [ 95 % confidence interval [ CI ] , 1.00 - 1.50 ] for total mortality and 1.34 [ 95 % CI , 1.03 - 1.75 ] for cardiovascular mortality ) . In the placebo group , the nighttime systolic BP ( 12 AM-6 AM ) more accurately predicted end points than the daytime level . Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP ( 10 % increase in night-to-day ratio ; HR for all cardiovascular end points , 1.41 ; 95 % CI , 1.03 - 1.94 ) . At r and omization , the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg ( 95 % CI , 128 - 156 mm Hg ) , 145 mm Hg ( 95 % CI , 126 - 164 mm Hg ) or 132 mm Hg ( 95 % CI , 120 - 145 mm Hg ) , respectively . In the active treatment group , systolic BP at r and omization did not significantly predict cardiovascular risk , regardless of the technique of BP measurement . CONCLUSIONS In untreated older patients with isolated systolic hypertension , ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP Syst-Eur is a multicentre placebo-controlled outcome trial , design ed by the European Working Party on High Blood Pressure in the Elderly ( EWPHE ) , to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension ( ISH ) . Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160 - 219 mmHg with a diastolic blood pressure less than 95 mmHg . The present paper in an interim report on the first 316 patients r and omized into this trial . The placebo ( N = 170 ) and active treatment ( N = 146 ) groups were similar at r and omization with respect to age ( 73 + /- 8 years ; mean + /- st and ard deviation ) , sitting blood pressure ( 178 + /- 12/85 + /- 7 mmHg ) , percentage men ( 34 % ) and percentage of patients with cardiovascular complications ( 29 % ) . After r and omization blood pressure fell more ( p < 0.001 ) on active treatment than in the placebo group ( 19 + /- 20/6 + /- 10 mmHg versus 7 + /- 19/1 + /- 10 mmHg for the sitting blood pressure ) . This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained . New centres are being recruited in order to r and omize a total of 3,000 patients
The reduction in cardiovascular mortality and morbidity was primarily due to a reduction in cerebrovascular mortality and morbidity .
AUTHORS ' CONCLUSIONS Treating healthy adults 60 years or older with moderate to severe systolic and /or diastolic hypertension with antihypertensive drug therapy reduced all-cause mortality , cardiovascular mortality and morbidity , cerebrovascular mortality and morbidity , and coronary heart disease mortality and morbidity .
Most evidence of benefit pertains to a primary prevention population using a thiazide as first-line treatment
BACKGROUND This is the second substantive up date of this review .
It was originally published in 1998 and was previously up date d in 2009 .
Elevated blood pressure ( known as ' hypertension ' ) increases with age - most rapidly over age 60 .
Systolic hypertension is more strongly associated with cardiovascular disease than is diastolic hypertension , and it occurs more commonly in older people .
It is important to know the benefits and harms of antihypertensive treatment for hypertension in this age group , as well as separately for people 60 to 79 years old and people 80 years or older .