***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 AND PURPOSE The relationship between blood pressure ( BP ) and heart rate ( HR ) and MRI assessment s of subcortical T2 hyperintensities was evaluated in healthy elderly men and women . METHODS  Casual and 24-hour ambulatory BPs and HR measurements  were taken of 144 elderly individuals , aged 55 to 79 years . Subjects had no evidence of previous health disorders .  MRI scans of white matter , subcortical gray matter , and insular subcortex were coded for severity of hyperintensities . RESULTS Mean casual BP for the group was 120/72 mm Hg . With age and sex accounted for , individuals with the highest severity rating of white matter hyperintensities had higher casual , awake , and sleep systolic BPs ; higher awake diastolic BPs ; greater awake systolic BP variability ; and a smaller nocturnal fall in systolic and diastolic BPs than individuals with less severe ratings . Higher severity ratings for subcortical gray matter hyperintensities were associated with elevations in casual , awake , and asleep systolic BPs and a smaller HR drop during sleep . Subjects with higher ratings for the insular subcortex had higher systolic and diastolic BPs ( casual , awake , and asleep ) , greater HR variability during sleep , and a smaller nocturnal fall in HR . CONCLUSIONS  Casual and 24-hour ambulatory BPs  and some ambulatory HR measures  are associated with subcortical lesions of the brain . Longitudinal studies are needed to further explore the relationship between white matter lesions and cardiovascular measures , as well as the significance of these lesions for cerebrovascular disease in healthy elderly subjects White matter hyperintensities ( WMH ) are associated with hypertension . We examined interactions among blood pressure ( BP ) , internal carotid artery ( ICA ) flow velocity parameters , and WMH . We obtained BP measurements from 694 community-dwelling subjects at mean ages 69.6 ( ±0.8 ) years and again at 72.6 ( ±0.7 ) years , plus brain MRI and ICA ultrasound at age 73±1 years . Diastolic and mean BP decreased and pulse pressure increased , but systolic BP did not change between 70 and 73 years . Multiple linear regression , corrected for vascular disease and risk factors , showed that WMH at the age of 73 years were associated with history of hypertension ( & bgr;=0.13 ; P<0.001 ) and with BP at the age of 70 years ( systolic & bgr;=0.08 , mean & bgr;=0.09 , diastolic & bgr;=0.08 ; all P<0.05 ) ; similar but attenuated associations were seen for BP at the age of 73 years . Lower diastolic BP and higher pulse pressure were associated with higher ICA pulsatility index at the age 73 years ( diastolic BP age 70 years : st and ardized & bgr;=−0.24 , P<0.001 ; pulse pressure age 70 years : & bgr;=0.19 , P<0.001 ) . WMH were associated with higher ICA pulsatility index ( & bgr;=0.13 ; P=0.002 ) after adjusting for BP and correction for multiple testing . Therefore , falling diastolic BP and increased pulse pressure are associated with increased ICA pulsatility index , which in turn is associated with WMH . This suggests that hypertension and WMH may either associate indirectly because hypertension increases arterial stiffness that leads to WMH over time , or coassociate through advancing age and stiffer vessels , or both . Reducing vascular stiffness may reduce WMH progression and should be tested in r and omized trials , in addition to testing antihypertensive therapy Summary Background Brain scans are essential to exclude haemorrhage in patients with suspected acute ischaemic stroke before treatment with alteplase .  However , patients with early ischaemic signs could be at increased risk of haemorrhage after alteplase treatment , and little information is available about whether pre-existing structural signs , which are common in older patients , affect response to alteplase . We aim ed to investigate the association between imaging signs on brain CT and outcomes after alteplase . Methods IST-3 was a multicentre , r and omised controlled trial of intravenous alteplase ( 0·9 mg/kg ) versus control within 6 h of acute ischaemic stroke . The primary outcome was independence at 6 months ( defined as an Oxford H and icap Scale [ OHS ] score of 0–2 ) . 3035 patients were enrolled to IST-3  and underwent prer and omisation brain CT . Experts who were unaware of the r and om allocation assessed scans for early signs of ischaemia ( tissue hypoattenuation , infa rct extent , swelling , and hyperattenuated artery ) and pre-existing signs ( old infa rct , leukoaraiosis , and atrophy ) . In this prespecified analysis , we assessed interactions between these imaging signs , symptomatic intracranial haemorrhage ( a secondary outcome in IST-3 ) and independence at 6 months , and alteplase , adjusting for age , National Institutes of Health Stroke Scale ( NIHSS ) score , and time to r and omisation . This trial is registered at IS RCT N.com , number IS RCT N25765518 . Findings 3017 patients were assessed in this analysis , of whom 1507 were allocated alteplase and 1510 were assigned control . A reduction in independence was predicted by tissue hypoattenuation ( odds ratio 0·66 , 95 % CI 0·55–0·81 ) , large lesion ( 0·51 , 0·38–0·68 ) , swelling ( 0·59 , 0·46–0·75 ) , hyperattenuated artery ( 0·59 , 0·47–0·75 ) , atrophy ( 0·74 , 0·59–0·94 ) , and leukoaraiosis ( 0·72 , 0·59–0·87 ) . Symptomatic intracranial haemorrhage was predicted by old infa rct ( odds ratio 1·72 , 95 % CI 1·18–2·51 ) , tissue hypoattenuation ( 1·54 , 1·04–2·27 ) , and hyperattenuated artery ( 1·54 , 1·03–2·29 ) . Some combinations of signs increased the absolute risk of symptomatic intracranial haemorrhage ( eg , both old infa rct and hyperattenuated artery , excess with alteplase 13·8 % , 95 % CI 6·9–20·7 ; both signs absent , excess 3·2 % , 1·4–5·1 ) . However , no imaging findings —individually or combined — modified the effect of alteplase on independence or symptomatic intracranial haemorrhage . Interpretation Some early ischaemic and pre-existing signs were associated with reduced independence at 6 months and increased symptomatic intracranial haemorrhage . Although no interaction was noted between brain imaging signs and effects of alteplase on these outcomes , some combinations of signs increased some absolute risks . Pre-existing signs should be considered , in addition to early ischaemic signs , during the assessment of patients with acute ischaemic stroke . Funding UK Medical Research Council , Health Foundation UK , Stroke Association UK , Chest Heart Stroke Scotl and , Scottish Funding Council SINAPSE Collaboration , and multiple governmental and philanthropic national funders Background —The prevalence of white matter hyperintensities ( WMHs ) detected on cerebral MRI is associated with hypertension , but it is not known whether blood pressure lowering can arrest their progression . We report here the results of an MRI sub study of PROGRESS ( Perindopril Protection Against Recurrent Stroke Study ) , a r and omized trial of blood pressure lowering in subjects with cerebrovascular disease . Methods and Results —The sub study comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months ( SD=6.0 months ) . At the first MRI , WMHs were grade d with a visual rating scale from A ( no WMH ) to D ( severe WMH ) . Participants were assigned to a combination of perindopril plus indapamide ( or their placebos ; 58 % ) or to single therapy with perindopril ( or placebo ) . At the time of the second MRI , the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure . Twenty-four subjects ( 12.5 % ) developed new WMHs at follow-up . The risk of new WMH was reduced by 43 % ( 95 % CI −7 % to 89 % ) in the active treatment group compared with the placebo group ( P=0.17 ) . The mean total volume of new WMHs was significantly reduced in the active treatment group ( 0.4 mm3 [ SE=0.8 ] ) compared with the placebo group ( 2.0 mm3 [ SE=0.7 ] ; P=0.012 ) . This difference was greatest for patients with severe WMH at entry , 0.0 mm3 ( SE=0 ) in the active treatment group versus 7.6 mm3 ( SE=1.0 ) in the placebo group ( P<0.0001 ) . Conclusions —These results indicate that an active blood pressure – lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease Background and Purpose — Short-term  blood pressure variability  ( BPV ) may predict outcome in acute stroke . We undertook a post hoc analysis of data from 2 r and omized controlled trials to determine the effect of short-term BPV on 2-week outcome . Methods — Controlling Hypertension and Hypotension Immediately Post Stroke ( CHHIPS ) was a trial of BP-lowering , enrolling 179 acute stroke patients ( onset < 36 hours ) . Continue or Stop Post-Stroke Antihypertensives Collaborative Study ( COSSACS ) compared a strategy of continuation versus temporarily stopping prestroke antihypertensive therapy in 763 acute stroke patients ( onset < 48 hours ) .  BPV  at baseline ( defined as SD , coefficient of variation , variation independent of the mean , and average real variability ) was derived from st and ardized casual cuff BP measures ( 6 readings < 30 minutes ) . Adjusted logistic regression models were used to assess the relation between BPV and death and disability ( modified Rankin scale>3 ) at 2 weeks . Results — Seven hundred six ( 92.5 % ) and 171 ( 95.5 % ) participants were included in the analysis for the COSSACS and CHHIPS data sets , respectively . Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set : COSSACS , odds ratio SD systolic BP 0.98 ( 0.78–1.23 ) ; CHHIPS , odds ratio SD systolic BP 0.97 ( 0.90–1.11 ) . Conclusions — When derived from casual cuff BP measures , short-term BPV is not a useful predictor of early ( 2 weeks ) outcome after acute stroke . Differing methodology may account for the discordance with previous studies indicating long-term ( casual BPV ) and short-term ( beat-to-beat BPV ) prognostic value . Clinical Trial Registration — COSSACS was registered on the International St and ard R and omised Controlled Trial Register ; URL : http://www.is rct n.com . Unique identifier : IS RCT N89712435 . CHHIPS was registered on the National Research Register ; URL : http://public.ukcrn.org.uk . Unique identifier : N0484128008 Background —  High blood pressure  (  BP ) is a risk factor for cerebrovascular disease , including stroke . Little is known about the importance of BP on the progression of microvascular disease of the brain , which has been associated with functional decline in mobility and cognition in older people . Methods and Results — This was a prospect i ve cohort of subjects 75 to 89 years of age to determine relations among vascular risk factors , white matter hyperintensity volume , and functional status . Ninety-nine subjects were enrolled through the use of a balanced 3 × 3 matrix stratified by age and mobility performance , and 72 subjects completed all sets of baseline and follow-up studies at 2 years . Subjects were excluded if there were medications or systemic or neurological diseases that could compromise mobility .  Ambulatory and clinic BP monitoring , magnetic resonance imaging , gait studies , and neuropsychological testing  were performed at baseline and after 24 months . Brain classification into normal white matter and T2-hyperintense white matter hyperintensity volume was performed with semiautomated segmentation . Quantitative measures of mobility and cognitive function were obtained longitudinally . Increased ambulatory systolic BP , but not clinic systolic BP , from baseline to 24 month follow-up was associated with increased white matter hyperintensity volume over that same period , as well as measures of executive function/processing speed . Similar associations were observed for 24-hour BP , awake BP , and sleep BP but not for the surge between the sleep and awake time at the 24-month time point . Conclusions — These data demonstrate for the first time the importance of 24-hour systolic BP in the pro 
    Output:
    
Conclusions On the basis of the available studies , BPV was associated with CSVD independent of mean blood pressure .