***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 Prospect i ve and case-control studies show that blood-pressure variability is an independent risk factor for severe organ damage and cardiovascular events in hypertensives . We prospect ively studied the association between systolic blood pressure variability and cardiovascular mortality and mortality from all causes in end-stage renal disease patients . METHODS AND RESULTS The subjects were 144 patients ( 86 men , 58 women ; mean age+/-SD , 52+/-13 years ) who underwent dialysis in the same dialysis centre and were examined for blood-pressure variability .  The study period was 38 months beginning in January 1995 , during which six cardiovascular and seven noncardiovascular fatalities occurred . Coefficient of variation in systolic blood pressure in 1994 , as an indicator of systolic blood pressure variability , ranged from 7.8 to 14.6 % . Cumulative incidence of death from all causes was related to coefficient of variation in systolic blood pressure . The difference between the maximum and minimum systolic blood pressure ( deltaSBP ) in 1994 ranged from 44 to 146 mmHg ( mean+/-SD , 78+/-13 mmHg ) and correlated significantly with coefficient of variation in systolic blood pressure ( r = 0.65 , P<0.0001 ) . Cox regression analysis was used to identify the independent predictors for mortality . The hazard ratio for death from all causes increased 1.63 times per 1 % increase in coefficient of variation in systolic blood pressure ( hazard ratio ; 95 % confidence interval : 1.63 ; 1.05 - 2.53 ) and 1.03 times per 1 mmHg increase in deltaSBP ( 1.08 ; 1.03 - 1.14 ) . CONCLUSION These results suggest that systolic blood pressure variability may be a significant prognostic factor in end-stage renal disease 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 BACKGROUND Analyses of some r and omised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected . We aim ed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk . METHODS The Anglo-Sc and inavian Cardiac Outcomes Trial Blood Pressure Lowering Arm ( ASCOT-BPLA ) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council ( MRC ) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65 - 74 years . We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as st and ard deviation ( SD ) and as transformations uncorrelated with mean blood pressure . For ASCOT-BPLA , we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring ( ABPM ) . RESULTS In ASCOT-BPLA , group systolic blood pressure ( SBP ) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits ( p<0.0001 ) , mainly because of lower within-individual visit-to-visit variability . Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group ( all p<0.0001 ) . Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group . The lower risk of stroke in the amlodipine group ( hazard ratio 0.78 , 95 % CI 0.67 - 0.90 ) was partly attenuated by adjusting for mean SBP during follow-up ( 0.84 , 0.72 - 0.98 ) , but was abolished by also adjusting for within-individual SD of clinic SBP ( 0.99 , 0.85 - 1.16 ) . Findings were similar for coronary events . In the ABPM sub study , reduced variability in daytime SBP in the amlodipine group ( p<0.0001 ) partly accounted for the reduced risk of vascular events , but reduced visit-to-visit variability in clinic SBP had a greater effect . In the MRC trial , group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up ( all p<0.0001 ) . Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk . INTERPRETATION The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure . To prevent stroke most effectively , blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability ; ideally they should reduce both 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 subjects Visit-to-visit blood pressure variability ( VTV-BPV ) is an independent risk factor for cardiovascular events and death in the general population . We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis , using data from a National Institutes of Health-sponsored r and omized trial ( the HEMO study ) . We used the coefficient of variation ( CV ) and the average real variability in systolic blood pressure ( SBP ) as metrics of VTV-BPV . In all , 1844 out of 1846 r and omized subjects had at least three visits with SBP measurements and were included in the analysis . Median follow-up was 2.5 years ( interquartile range 1.3–4.3 years ) , during which time there were 869 deaths from any cause and 408 ( adjudicated ) cardiovascular deaths . The mean pre-dialysis SBP CV was 9.9±4.6 % . In unadjusted models , we found a 31 % higher risk of death from any cause per 10 % increase in VTV-BPV . This association was attenuated after multivariable adjustment but remained statistically significant . Similarly , we found a 28 % higher risk of cardiovascular death per 10 % increase in VTV-BPV , which was attenuated and no longer statistically significant in fully adjusted models . The associations among VTV-BPV , death and cardiovascular death were modified by baseline SBP . In a diverse , well-dialyzed cohort of patients on maintenance hemodialysis , VTV-BPV , assessed using metrics of variability in pre-dialysis SBP , was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality , particularly in patients with a lower baseline SBP Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo .  Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial Objective : To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses . Background : Visit-to-visit SBP variability correlates with cardiovascular events . However , the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood . Methods and results : A total of 485 patients with essential hypertension from the Non-In 
    Output:
    
In summary , modest associations between visit-to-visit variability of BP and CVD and all-cause mortality are present in published studies .