Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality Effects of different antihypertensive drugs on blood pressure variability in patients with ischemic stroke. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population Dementia risk with antihypertensive use and blood pressure variability Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study. Impact of visit-to-visit variability and systolic blood pressure control on subsequent outcomes in hypertensive patients with coronary artery disease (from the HIJ-CREATE substudy). Long-term prognostic implications of visit-to-visit blood pressure variability in patients with ischemic stroke. The prognostic value of long-term visit-to-visit blood pressure variability on stroke in real-world practice: a dynamic cohort study in a large representative sample of Chinese hypertensive population. Redefined Blood Pressure Variability Measure and Its Association With Mortality in Elderly Primary Care Patients Alteration of vascular function is an important factor in the correlation between visit-to-visit blood pressure variability and cardiovascular disease Effect of calcium antagonists on ambulatory blood pressure and its variations. Blood pressure 1 year after stroke: the need to optimize secondary prevention. Short-Term Blood Pressure Variability in Acute Stroke: Post Hoc Analysis of the Controlling Hypertension and Hypotension Immediately Post Stroke and Continue or Stop Post-Stroke Antihypertensives Collaborative Study Trials The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension Randomized Controlled Trial of a Multipronged Intervention to Improve Blood Pressure Control among Stroke Survivors in Nigeria Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study
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 Context It is not clear whether variability in a patient 's outpatient blood pressure ( BP ) measurements has prognostic importance . Contribution Patients with greater visit-to-visit variability in BP readings had an increased risk for cardiovascular events and mortality , which was independent of their overall degree of BP control . Implication Further studies are warranted to assess whether reducing visit-to-visit BP variations will alter the risk for adverse cardiovascular outcomes . The prognostic value of blood pressure ( BP ) is mainly based on measurements obtained in a clinical setting , typically from a few visits ( 1 ) . Until recently , variability of BP across outpatient visits was dismissed as r and om fluctuation around a patient 's true underlying BP ( 2 , 3 ) . Although some studies have reported associations between higher visit-to-visit variability ( VVV ) of systolic BP ( SBP ) and an increased risk for stroke and coronary heart disease ( CHD ) , other analyses have failed to show such associations ( 410 ) . The method applied in estimating VVV of BP varied widely across previous studies . In addition , studies have used as few as 3 visits and as many as 56 visits to estimate the VVV of BP , and the time between visits has ranged from 2 days to as long as 4 years ( 5 , 11 , 12 ) . These factors not only influence VVV of BP but could also affect the strength of its association with cardiovascular disease ( CVD ) outcomes ( 4 , 13 ) . To address the inconsistent findings from previous studies , we did a secondary data analysis of ALLHAT ( Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ) to examine whether VVV of BP is associated with CVD and mortality events . ALLHAT provides the opportunity to evaluate the association between VVV of BP and major clinical outcomes in a large and diverse population with hypertension in which visits were conducted at set time intervals , BP was measured by following a st and ardized protocol , and outcomes were evaluated over several years of follow-up . Methods Study Design We did a cohort study as a secondary analysis using data from ALLHAT . Figure 1 shows the timeline for assessment of VVV of BP and outcome events within ALLHAT . The primary exposure of interest , VVV of SBP , was ascertained at the 7 study visits conducted between 6 and 28 months after r and omization . We studied 4 outcomes : fatal CHD or nonfatal myocardial infa rct ion ( MI ) , all-cause mortality , stroke , and heart failure . Participants were followed from their 28-month visit until the occurrence of an outcome event or the end of active ALLHAT follow-up ( October 2001 to March 2002 ) . Participants who had an event before their 28-month visit were excluded from all analyses . Figure 1 . Study design evaluating the association between VVV of BP and cardiovascular outcomes and all-cause mortality in ALLHAT . ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ; BP = blood pressure ; DBP = diastolic blood pressure ; SBP = systolic blood pressure ; VVV = visit-to-visit variability . * Participants were followed for a mean of 2.7 to 2.9 y ( maximum , 5.7 y ) depending on the outcome after assessment of VVV of BP . ALLHAT was a multicenter , double-blind , r and omized clinical trial sponsored by the National Heart , Lung , and Blood Institute of the National Institutes of Health . A complete description of the rationale and design of ALLHAT has been previously published ( 14 ) . In brief , ALLHAT was design ed to determine whether treatment initiated with a calcium-channel blocker ( amlodipine ) , angiotensin-converting enzyme inhibitor ( lisinopril ) , or -blocker (doxazosin)each compared with treatment initiated with a diuretic (chlorthalidone)would lower major cardiovascular outcomes . The primary end point was incidence of fatal CHD or nonfatal MI .  A total of 42418 hypertensive adults aged 55 years or older with 1 or more additional risk factor for CVD were enrolled at 623 clinical sites across the United States , Canada , Puerto Rico , and the U.S. Virgin Isl and s between February 1994 and January 1998 . The doxazosin treatment group was discontinued in 2000 because of the small chance of finding a benefit on CHD outcomes and an increased risk for CVD than in the chlorthalidone group ( 15 ) . The main results comparing participants r and omly assigned to chlorthalidone , amlodipine , or lisinopril were published in December 2002 ( 16 ) . The trial was approved by local institutional review boards , and all participants provided written informed consent . Our current analysis was approved by the Institutional Review Board at the University of Alabama at Birmingham . Study Visits , BP Measurements , and Calculation of VVV of BP To calculate intraindividual VVV of SBP and diastolic BP ( DBP ) , we used data from 7 follow-up visits that occurred 6 , 9 , 12 , 16 , 20 , 24 , and 28 months after r and omization . We chose to begin the assessment period at the 6-month follow-up visit to avoid confounding by the initial reduction in BP that occurred between r and omization and this visit ( SBP , 6 to 10 mm Hg ; DBP , approximately 5 mm Hg ) due to early medication titration . To increase the precision of estimates , we calculated VVV of BP for participants with BP measurements at 5 , 6 , or 7 visits conducted between month 6 and 28 after r and omization . The VVV of BP was imputed for participants who attended fewer than 5 visits between months 6 and 28 . To maximize follow-up time , we did not extend the assessment past the 28-month follow-up visit . At each follow-up visit ,  BP was measured twice by a trained observer by means of a st and ardized technique ( 17 ) . Using the average BP at each visit , we defined VVV of BP by the intraindividual SD across visits . Average real variability ( ARV ) and SD independent of the mean ( SDIM ) were calculated as alternative metrics for VVV of BP ( Appendix Figure ) ( 18 ) . The VVV of DBP was also calculated in secondary analyses . Appendix Figure . Formulas used to calculate VVV of BP metrics . ARV = average real variability ; BP = blood pressure ; SDIM = SD independent of the mean ; VVV = visit-to-visit variability . Outcome Ascertainment We studied 4 outcomes , including fatal CHD or nonfatal MI , all-cause mortality , stroke , and heart failure . The event ascertainment process is detailed elsewhere ( 14 , 16 ) . Participants were followed from the end of the assessment period to the date of each outcome , their date of death , or the end of active ALLHAT follow-up ( 1 October 2001 through 31 March 2002 ) . Covariate Information Covariates used for adjustment were selected a priori on the basis of their potential role as confounders . Baseline ( before r and omization ) variables included age , sex , race/ethnicity , education , current cigarette smoking status , body mass index , use of aspirin , high-density lipoprotein cholesterol level less than 0.91 mmol/L ( < 35 mg/dL ) ( at 2 occasions in the 5 years before ALLHAT enrollment ) ,  total cholesterol level , estimated glomerular filtration rate ( eGFR ) , diabetes , history of MI or stroke , documentation of other atherosclerotic CVD , history of revascularization , atrial fibrillation by electrocardiography , left ventricular hypertrophy ( LVH ) , the presence of ST depression and T-wave inversion , and use of antihypertensive medication  before ALLHAT r and omization . The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation ( 19 ) . Data collected at visits conducted 6 to 28 months after r and omization were used to calculate mean SBP and DBP ; pulse pressure ; the use of antihypertensive medications beyond the r and omization drug ; changes in antihypertensive medication regimen ( adding , stopping , or changing antihypertensive medications ) ; use of statins ; and low adherence , which is defined as a report of a participant receiving less than 80 % of the r and omization drug at any visit between months 6 and 28 . Participants who reported taking 80 % or more of their r and omization drug at every visit between months 6 and 28 were considered to have high adherence . Statistical Analysis Because of limited follow-up available after the assessment period for participants r and omly assigned to receive doxazosin , we restricted our analyses to the 33357 ALLHAT participants r and omly assigned to receive chlorthalidone , amlodipine , or lisinopril .  We excluded 7543 participants who had CVD events or died before the 28-month visit . We imputed VVV of BP for participants with fewer than 5 visits and BP measurements between months 6 and 28 of follow-up . In addition , missing data for covariates were imputed ( Appendix Table 1 ) . Imputation was performed with 10 data sets using chained equations . Appendix Table 1 . Percentage of Missing Data for Participants Included in the Current Analyses Characteristics of participants included in the current analyses were calculated after participants were stratified into a quintile of SD of SBP . The KaplanMeier method was used to calculate the cumulative incidence of each outcome by quintile of SD of SBP . Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios ( HRs ) for each outcome associated with a quintile of SD of SBP , with the lowest quintile serving as the reference . Four nested models were constructed . Model 1 included adjustment for age , race/ethnicity , sex , region of residence , and antihypertensive r and omization assignment . Model 2 includes the variables in model 1 and additional adjustment for education , smoking status , body mass index , use of aspirin , low high-density lipoprotein cholesterol level , total cholesterol level , eGFR , diabetes , history of MI or stroke , history of other atherosclerotic CVD , history of coronary revascularization , atrial fibrillation by electrocardiography , major ST depression or T-wave inversion , LVH , use of antihypertensive medications before ALLHAT r and omization , and  statin use during the assessment period ( months 6 through 28 of follow-up ) . Model 3 includes the variables in model 2 and additional adjustment for mean pulse pressure , OBJECTIVE Blood pressure variation is one of the factors that affects the risk of stroke recurrence and prognosis . This study investigates the effects of calcium channel blockers and beta-blockers on blood pressure variability in severe ischemic stroke patients . PATIENTS AND METHODS The clinical data of 24 patients with ischemic stroke in our intensive care unit were analyzed , and received amlodipine or metoprolol for more than 14 days with 24-hour ambulatory blood pressure monitoring .  All patients aged 61 - 90 years , with GCS score ≤ 8 or associated with other organ dysfunction . RESULTS Among these 24 ischemic stroke patients , 12 received amlodipine and 12 received metoprolol . The observation period was divided into two phases : 1 - 6 days and 7 - 14 days . The decrease in blood pressure was faster in the metoprolol group than in the amlodipine group , while the average st and ard deviation was significantly greater and the smoothness index was less . CONCLUSIONS Metoprolol has faster onset  than amlodipine  and less blood pressure variability than metoprolol 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 determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability ( BPV ) in the preceding 4 years . Methods : A total of 6,537 participants ( mean age 79 years , 62 % women ) in a prospect i ve population -based cohort were followed up for incident dementia . A 4-year time lag period was created to classify drug exposure and measure blood pressure . BPV ( percent coefficient of variation [ CV ] ) was regressed against 9 antihypertensive drug classes ( BPVreg ) . Cox regression models were employed to determine hazard ratios ( HRs ) for incident dementia thereafter according to drug class , adjusted for mean blood pressure , covariates , and BPV or BPVreg . Results : Over a median 8.4 years follow-up ( interquartile range 6.7–9.0 ) , lower dementia risk was associated with nondihydropyridine calcium channel blocker ( HR 0.56 ; 95 % confidence interval [ CI ] 0.31–1.00 , p = 0.05 ) and loop diuretics ( HR 0.45 ; 95 % CI 0.22–0.93 , p = 0.03 ) after adjusting for CV-BPV . Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker ( HR 0.52 ; 95 % CI 0.28–0.95 , p = 0.03 ) and loop diuretics ( HR 0.40 ; 95 % CI 0.19–0.83 , p = 0.01 ) . All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05 . Conclusions : Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years . Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk BACKGROUND Recent data have highlighted shortcomings of the usual blood pressure ( BP ) hypothesis in several population s , and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events . Herein , we aim ed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure ( CHF ) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan ( HEAAL ) . METHODS AND RESULTS The HEAAL study r and omized 3834 patients with HF and reduced ejection fraction administered 150 mg or 50 mg losartan daily in a double blind , r and omized , controlled trial . The patients were followed up for up to 6.8 years after r and omization , and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter . Three measures of visit-to-visit BP variability were computed for each subject : the st and ard deviation , the coefficient of variation and the average absolute visit-to-visit variation . Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure , baseline covariates and the time to death or heart failure hospitalization ( i.e. primary outcome ) . In multivariate analyses stratified on baseline BP , the patients with higher visit-to visit BP variability exhibited poorer outcomes ( average absolute difference in SBP in mmHg : hazard ratio : 1.023 [ 95 % CI ( 1.013 , 1.034 ) , P<0.0001 ] ) , independent from high dose losartan ( still beneficial ) . CONCLUSIONS For the first time , visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction , and associated with poorer cardiovascular outcomes . Such assessment s should be prioritized for testing prevention strategies in CHF . CLINICAL TRIAL REGISTRATION This study is registered with the Clinical Trials.gov , number NCT00090259 Although visit-to-visit variability in systolic blood pressure ( BP ) is a strong predictor of stroke , the impact on subsequent major adverse cardiac events ( MACEs ) in patients with coronary artery disease ( CAD ) in terms of secondary prevention remains unclear . The aim of this study was to clarify the prognostic significance of visit-to-visit variability  in systolic BP  on subsequent MACE in hypertensive patients with CAD . In the Heart Institute of Japan C and esartan R and omised Trial for Evaluation in Coronary Artery Disease , a total of 2,049 hypertensive patients with CAD were enrolled . Incidence of MACEs in addition to biochemistry tests and office BP were determined during follow-up . Achieved BP was defined as the mean value of systolic BP in patients who did not experience MACE and the mean value of systolic BP before MACE in those who experienced MACE during follow-up . In the present study , 1,734 patients had multiple follow-up visits ( ≥3 times ) until their final follow-up . During a median follow-up of 4.2 years , the primary outcome occurred in 317 patients ( 18.3 % ) . Visit-to-visit variability of systolic BP was defined as the SD . Participants were divided into equal quartiles based on the mean systolic BP during follow-up and visit-to-visit variability of systolic BP , respectively . Although there was no relation between visit-to-visit variability of systolic BP and the incidence of MACE , the highest quartile based on mean systolic BP showed a significant relation with subsequent MACE . In conclusion , in hypertensive patients with CAD , inadequate BP control is a strong predictor of subsequent MACE , whereas visit-to-visit variability of systolic BP is not BACKGROUND Blood pressure ( BP ) variability ( BPV ) is a novel risk factor for the development of atherosclerotic diseases . High BPV has recently been shown to predict all-cause and cardiovascular mortality in patients with lacunar infa rct . Whether BPV has prognostic implication s in patients with ischemic stroke subtypes , other than those due to small-vessel occlusion , remains uncertain . METHODS We prospect ively followed up the clinical outcome of 632 consecutive ischemic stroke patients without atrial fibrillation . The average BP and BPV , as determined by the coefficient of variation of the systolic and diastolic BP , were recorded during a mean 12 ± 6 outpatient clinic visits . RESULTS The average age of the population was 71 ± 11 years . After a mean of 76 ± 18 months of follow-up , 161 patients died ( 26 % ) ; 35 % ( n = 56 of 161 ) of these deaths were due to cardiovascular causes . Sixteen percent and 5 % developed recurrent stroke and acute coronary syndrome ( ACS ) , respectively . After adjusting for mean systolic BP and confounding variables , patients with high systolic BPV were at significantly greater risk of cardiovascular mortality ( hazards ratio ( HR ) = 2.36 ; 95 % confidence interval ( CI ) = 1.02 - 5.49 ; P < 0.05 ) . High systolic BPV also predicted all-cause mortality after adjusting for mean systolic BP ( HR = 1.79 ; 95 % CI = 1.16 - 2.75 ; P < 0.05 ) . There was no association between systolic BPV and nonfatal recurrent stroke or nonfatal ACS . Raised diastolic BPV did not predict recurrent nonfatal stroke , nonfatal ACS , or mortality . CONCLUSIONS Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality in patients with ischemic stroke without atrial fibrillation , independent of other conventional risk factors , including average BP control 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 Visit-to-visit  blood pressure ( BP ) variability has received considerable attention recently . The objective of our study is to define a variability measure that is independent of change over time and determine the association between longitudinal summary measures of BP measurements and mortality risk . Data for the study came from a prospect i ve cohort of 2906 adults , aged ≥60 years , in an urban primary care system with ⩽15 years of follow-up . Date s of death for deceased participants were retrieved from the National Death Index .  Systolic and diastolic BP measurements from outpatient clinic visits were extracted from the Regenstrief Medical Record System . For each patient , the intercept , regression slope , and root mean square error for visit-to-visit variability were derived using linear regression models and used as independent variables in Cox proportional hazards models for both all-cause mortality and mortality attributable to coronary heart disease or stroke . Rate of change was associated with mortality risk in a U-shaped relationship and that participants with little or no change in BP had the lowest mortality risk . BP variability was not an independent predictor of mortality risk . By separating change over time from visit-to-visit variability in studies with relatively long follow-up , we demonstrated in this elderly primary care patient population that BP changes over time , not variability , were associated with greater mortality risk . Future research is needed to confirm our findings in other population 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-Invasive Atherosclerotic Evaluation in Hypertension ( NOAH ) study cohort were included . We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters . Next , we prospect ively examined the correlation of SBP variability and frequency of cardiovascular disease ( CVD ) and total mortality . Patients with higher SBP variability exhibited significantly higher rates of statin use , as well as higher pulse wave velocity ( PWV ) , left-ventricular mass index ( LVMI ) , plaque score , and resistive index of the common carotid artery ; these patients also exhibited lower estimated glomerular filtration rate . Kaplan – Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate . The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima – media thickness , plaque score , and resistive index , and was slightly diminished after adjustment for PWV and LVMI . Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment . Conclusion : Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change , incidence of CVD , and mortality rate . Altered arterial functions , such as macrovascular atherosclerosis and vascular resistance , are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD Our previous studies have shown that blood pressure variability is not linked to activity of the adrenergic nervous system but that a small part of the variation is due to vagal nervous tone . The present work investigates whether myogenic activity of blood vessels could be responsible for the blood pressure variations . To test this hypothesis , variability was measured before and after administration of nifedipine , known to decrease spontaneous vascular contractions . In 17 patients with moderate essential hypertension , blood pressure was measured every 30 min for 12 h with a device recording Korotkoff 's sounds on tape . Blood pressure variability was defined as the st and ard deviation of the mean of all readings . Placebo , nifedipine ( 20 mg b.i.d . in a slow-release formulation ) alone and in combination with atenolol ( 50 mg b.i.d . ) , and atenolol alone were given double-blind for 3 weeks each . At the end of each period , a 12 h blood pressure profile was recorded . Systolic blood pressure significantly decreased with any of the drugs used ; the combination of nifedipine and atenolol caused a greater decrease than that of any of the drugs alone . Diastolic blood pressure only decreased with the combination of nifedipine and atenolol . Nifedipine did not cause significant changes in systolic or diastolic variability ; a small but nonsignificant decrease in diastolic variability was seen with atenolol and the combination of atenolol and nifedipine . The present data do not support the hypothesis that blood pressure variability is linked to myogenic vascular activity because no decrease in blood pressure variability was seen with nifedipine Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P < .0001 ) . The proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up 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 In patients with insufficient blood pressure ( BP ) control , despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker ( CCB ) , whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear . We conducted a multicenter r and omized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan ( 100 mg ) and amlodipine ( 5 mg ) to irbesartan ( 100 mg ) with an increased dose of amlodipine ( 10 mg ) ( HD group , n=62 ) or irbesartan ( 100 mg ) and amlodipine ( 5 mg ) with 1 mg of indapamide ( D group , n=63 ) in patients with poorly controlled hypertension .  BP measured at home was monitored by a physician using a telemonitoring system . Between the HD and D groups , no significant differences were observed in morning home BP changes ( mean reduction of systolic/diastolic BP , 1.7/0.9 mmHg ; 95 % confidence intervals , −2.4 to 5.7/−1.4 to 3.2 ; P=0.19/0.37 ) , achievement rate of target BP ( 45.2 % vs. 42.9 % , P=0.80 ) , BP variability independent of the mean ( P⩾0.74 ) , other variability indices ( P⩾0.55 ) and time to stabilization , which was calculated using a fitted analysis ( 13.1 days vs. 11.4 days , P=0.99 ) . Although a significant increase in serum uric acid was observed in the D group ( P<0.0001 ) , neither clinical ly relevant abnormal laboratory test results nor critical BP changes were observed throughout the trial period . Both antihypertensive drug combination strategies were effective treatment options . Further investigation is required to determine the appropriate use of both therapies based on the various pathologies associated with hypertension Rationale Stroke is the second-leading cause of death in low- and middle-income countries , but use of evidence -based therapies for stroke prevention in such countries , especially those in Africa , is extremely poor . This study is design ed to enhance the implementation and sustainability of secondary stroke-preventive services following hospital discharge . Aim /Hypothesis The primary study aim is to test whether a Chronic Care Model-based initiative entitled the Tailored Hospital-based Risk reduction to Impede Vascular Events after Stroke ( THRIVES ) significantly improves blood pressure control after stroke . Design This prospect i ve triple-blind r and omized controlled trial will include a cohort of 400 patients with a recent stroke discharged from four medical care facilities in Nigeria . The culturally sensitive , system-appropriate intervention comprises patient report cards , phone text messaging , an educational video , and coordination of posthospitalization care . Study Outcomes The primary outcome is improvement of blood pressure control . Secondary endpoints include control of other stroke risk factors , medication adherence , functional status , and quality of life . We will also perform a cost analysis of THRIVES from the viewpoint of government policy-makers . Discussion We anticipate that a successful intervention will serve as a scalable model of effective postdischarge chronic blood pressure management for stroke in sub-Saharan Africa and possibly for other symptomatic cardiovascular disease entities in the region Objective To investigate the association between visit-to-visit variability in blood pressure and  cognitive function in old age ( > 70 years ) . Design Prospect i ve cohort study . Setting PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) study , a collaboration between centres in Irel and , Scotl and , and the Netherl and s. Participants 5461 participants , mean age 75.3 years , who were at risk of cardiovascular disease .  Blood pressure was measured every three months during an average of 3.2 years . Visit-to-visit variability in blood pressure was defined as the st and ard deviation of blood pressure measurements between visits . Main outcome measures Four domains of cognitive function , testing selective attention , processing speed , and immediate and delayed memory . In a magnetic resonance imaging sub study of 553 participants , structural brain volumes , cerebral microbleeds , infa rcts , and white matter hyperintensities were measured . Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests : attention ( mean difference high versus low thirds ) 3.08 seconds ( 95 % confidence interval 0.85 to 5.31 ) , processing speed −1.16 digits coded ( 95 % confidence interval −1.69 to −0.63 ) , immediate memory −0.27 pictures remembered ( 95 % confidence interval −0.41 to −0.13 ) , and delayed memory −0.30 pictures remembered ( 95 % confidence interval −0.49 to −0.11 ) . Furthermore , higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infa rcts , and higher variability in diastolic blood pressure was associated with cerebral microbleeds ( all P<0.05 ) . All associations were adjusted for average blood pressure and cardiovascular risk factors . Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age
Effects of antihypertensive drugs on SBP variability are dose-dependent and persist when used in combinations .
Use of a high dose of a calcium channel blocker alone or in combination with other agents is therefore likely to be particularly effective in prevention of stroke
BACKGROUND AND PURPOSE Recent studies have shown that visit-to-visit blood pressure variability is a powerful risk factor for stroke , is reduced by calcium channel blockers and diuretics , and increased by β-blockers .
However , it is unknown whether these effects are dose-dependent and persist in combination with other drugs .