***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 In previous studies , of which several were underpowered , the relation between cardiovascular outcome and blood pressure ( BP ) variability was inconsistent . We followed health outcomes in 8938 subjects ( mean age : 53.0 years ; 46.8 % women ) r and omly recruited from 11 population s. At baseline , we assessed BP variability from the SD and average real variability in 24-hour ambulatory BP recordings . We computed st and ardized hazard ratios ( HRs ) while stratifying by cohort and adjusting for 24-hour BP and other risk factors . Over 11.3 years ( median ) , 1242 deaths ( 487 cardiovascular ) occurred , and 1049 , 577 , 421 , and 457 participants experienced a fatal or nonfatal cardiovascular , cardiac , or coronary event or a stroke . Higher diastolic average real variability in 24-hour ambulatory BP recordings predicted ( P≤0.03 ) total ( HR : 1.14 ) and cardiovascular ( HR : 1.21 ) mortality and all types of fatal combined with nonfatal end points ( HR : ≥1.07 ) with the exception of cardiac and coronary events ( HR : ≤1.02 ; P≥0.58 ) . Higher systolic average real variability in 24-hour ambulatory BP recordings predicted ( P<0.05 ) total ( HR : 1.11 ) and cardiovascular ( HR : 1.16 ) mortality and all fatal combined with nonfatal end points ( HR : ≥1.07 ) , with the exception of cardiac and coronary events ( HR : ≤1.03 ; P≥0.54 ) . SD predicted only total and cardiovascular mortality . While accounting for the 24-hour BP level , average real variability in 24-hour ambulatory BP recordings added < 1 % to the prediction of a cardiovascular event . Sensitivity analyses considering ethnicity , sex , age , previous cardiovascular disease , antihypertensive treatment , number of BP readings per recording , or the night : day BP ratio were confirmatory . In conclusion , in a large population cohort , which provided sufficient statistical power , BP variability assessed from 24-hour ambulatory recordings did not contribute much to risk stratification over and beyond 24-hour BP BACKGROUND The prognostic significance of long-term visit-to-visit blood pressure variability ( BPV ) has not yet been vali date d in " real world " hypertensive patients . The aim of the current study is to explore the prognostic value of BPV on stroke in hypertensive patients . METHODS This was a dynamic prospect i ve cohort study based on electronic medical records in Shanghai , China . Hypertensive patients ( N=122,636 ) without history of stroke at baseline , were followed up from 2005 to 2011 . The cohort comprised of 4522 stroke patients and 118,114 non-stroke patients during a mean follow-up duration of 48 months .  BPV was measured by st and ard deviation ( SD ) and the coefficient of variation ( CV ) of blood pressure . RESULTS The visit-to-visit variability of both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) was independently associated with the occurrence of stroke [ SD : the hazard ratios ( 95 % confidence intervals ) of SBP and DBP were 1.042 ( 1.021 to 1.064 ) and 1.052 ( 1.040 to 1.065 ) ; CV : the hazard ratios ( 95 % confidence intervals ) of SBP and DBP were 1.183 ( 1.010 to 1.356 ) and 1.151 ( 1.005 to 1.317 ) , respectively ] . The hazard ratio values increased along with an increase of the BPV levels of SBP and DBP . The increment effect remained significant after controlling the blood pressure control status of subjects . CONCLUSIONS Increased BPV of both SBP and DBP , independent of the average blood pressure , is a predictor of stroke among community hypertensive patients in real-world clinical practice . The risk of stroke increased along with increased BPV . Stabilizing BPV might be a therapeutic target in hypertension Background — Recent evidence suggests that visit-to-visit variability in systolic blood pressure ( SBP ) and maximum SBP are predictors of cardiovascular disease . However , it remains uncertain whether these parameters predict the risks of macrovascular and microvascular complications in patients with type 2 diabetes mellitus . Methods and Results — The Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) was a factorial r and omized controlled trial of blood pressure lowering and blood glucose control in patients with type 2 diabetes mellitus . The present analysis included 8811 patients without major macrovascular and microvascular events or death during the first 24 months after r and omization .  SBP variability ( defined as st and ard deviation ) and maximum SBP were determined during the first 24 months after r and omization . During a median 2.4 years of follow-up from the 24-month visit , 407 major macrovascular ( myocardial infa rct ion , stroke , or cardiovascular death ) and 476 microvascular ( new or worsening nephropathy or retinopathy ) events were observed . The association of major macrovascular and microvascular events with SBP variability was continuous even after adjustment for mean SBP and other confounding factors ( both P<0.05 for trend ) . Hazard ratios ( 95 % confidence intervals ) for the highest tenth of SBP variability were 1.54 ( 0.99–2.39 ) for macrovascular events and 1.84 ( 1.19–2.84 ) for microvascular events in comparison with the lowest tenth . For maximum SBP , hazard ratios ( 95 % confidence intervals ) for the highest tenth were 3.64 ( 1.73–7.66 ) and 2.18 ( 1.04–4.58 ) , respectively . Conclusion — Visit-to-visit variability in SBP and maximum SBP were independent risk factors for macrovascular and microvascular complications in type 2 diabetes mellitus . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique Identifier : NCT00145925 The hypothesis has been advanced that cardiovascular prognosis is related not only to 24-hour mean blood pressure but also to blood pressure variability . Data , however , are inconsistent , and no long-term prognostic study is available . In 2012 individuals r and omly selected from the population of Monza ( Milan ) , 24-hour ambulatory blood pressure ( Spacelabs 90207 ) was measured via readings spaced by 20 minutes .  Systolic and diastolic blood pressure variability was obtained by calculating the following : ( 1 ) the SD of 24-hour , day , and night mean values ; ( 2 ) the day – night blood pressure difference ; and ( 3 ) the residual or  erratic blood pressure variability  ( Fourier spectral analysis ) . Fatal cardiovascular and noncardiovascular events were registered for 148 months . When adjusted for age , sex , 24-hour mean blood pressure , and other risk factors , there was no relationship between the risk of death and 24-hour , day , and night blood pressure SDs . In contrast , the adjusted risk of cardiovascular death was inversely related to day – night diastolic BP difference ( & bgr ; coefficient=−0.040 ; P<0.02 ) and showed a significant positive relationship with residual diastolic blood pressure variability ( & bgr ; coefficient=0.175 ; P<0.002 ) . Twenty-four – hour mean blood pressure attenuation of nocturnal hypotension and erratic diastolic blood pressure variability all independently predicted the mortality risk , with the erratic variability being the most important factor . Our data show that the relationship of blood pressure to prognosis is complex and that phenomena other than 24-hour mean values are involved . They also provide the first evidence that short-term erratic components of blood pressure variability play a prognostic role , with their increase being accompanied by an increased cardiovascular risk Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects , but relevant data for older individuals are sparse . We analysed data from the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) study of 5804 participants aged 70–82 years with a history of , or risk factors for cardiovascular disease . Visit-to-visit variability in blood pressure ( st and ard deviation ) was determined using a minimum of five measurements over 1 year ; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up ; longer-term follow-up ( mean 7.1 years ) was available for 1808 subjects .  Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality ( hazard ratio per 5 mmHg increase in st and ard deviation of systolic blood pressure = 1.2 , 95 % confidence interval 1.1–1.4 ; hazard ratio 1.1 , 95 % confidence interval 1.1–1.2 , respectively ) . Variability in diastolic blood pressure associated with increased risk for coronary events ( hazard ratio 1.5 , 95 % confidence interval 1.2–1.8 for each 5 mmHg increase ) , heart failure hospitalisation ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.8 ) and vascular ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.7 ) and total mortality ( hazard ratio 1.3 , 95 % confidence interval 1.1–1.5 ) , all in long-term follow-up . Pulse pressure variability was associated with increased stroke risk ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.4 for each 5 mmHg increase ) , vascular mortality ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.3 ) and total mortality ( hazard ratio 1.1 , 95 % confidence interval 1.0–1.2 ) , all in long-term follow-up . All associations were independent of respective mean blood pressure levels , age , gender , in-trial treatment group ( pravastatin or placebo ) and prior vascular disease and cardiovascular disease risk factors . Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk 
    Output:
    
Long term variability in blood pressure is associated with cardiovascular and mortality outcomes , over and above the effect of mean blood pressure .
Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease .
Limited data for mid-term and short term variability showed similar associations .