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      Impact of Circadian Blood Pressure Pattern on Silent Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis


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          Abnormal circadian blood pressure ( BP) variations during sleep, specifically the non‐dipping (<10% fall in nocturnal BP) and reverse‐dipping patterns (rise in nocturnal BP), have been associated with an increased risk of cardiovascular events and target organ damage. However, the relationship between abnormal sleep BP variations and cerebral small vessel disease markers is poorly established. This study aims to assess the association between non‐dipping and reverse‐dipping BP patterns with markers of silent cerebral small vessel disease.

          Methods and Results

          MEDLINE, Embase, and Cochrane Databases were searched from inception through November 2019. Studies that reported the odds ratios (ORs) for cerebral small vessel disease markers in patients with non‐dipping or reverse‐dipping BP patterns were included. Effect estimates from the individual studies were extracted and combined using the random‐effect, generic inverse variance method of DerSimonian and Laird. Twelve observational studies composed of 3497 patients were included in this analysis. The reverse‐dipping compared with normal dipping BP pattern was associated with a higher prevalence of white matter hyperintensity with a pooled adjusted OR of 2.00 (95% CI, 1.13–2.37; I 2=36%). Non‐dipping BP pattern compared with normal dipping BP pattern was associated with higher prevalence of white matter hyperintensity and asymptomatic lacunar infarction, with pooled ORs of 1.38 (95% CI, 0.95–2.02; I 2=52%) and 2.33 (95% CI, 1.30–4.18; I 2=73%), respectively. Limiting to only studies with confounder‐adjusted analysis resulted in a pooled OR of 1.38 (95% CI, 0.95–2.02; I 2=52%) for white matter hyperintensity and 1.44 (95% CI, 0.97–2.13; I 2=0%) for asymptomatic lacunar infarction.


          The non‐dipping and reverse‐dipping BP patterns are associated with neuroimaging cerebral small vessel disease markers.

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          Most cited references 39

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          Blood pressure and clinical outcomes in the International Stroke Trial.

          Among patients with acute stroke, high blood pressure is often associated with poor outcome, although the reason is unclear. We analyzed data from the International Stroke Trial (IST) to explore the relationship between systolic blood pressure (SBP), subsequent clinical events over the next 2 weeks, and functional outcome at 6 months in patients with acute stroke. We included in the analysis 17 398 patients from IST with confirmed ischemic stroke. A single measurement of SBP was made immediately before randomization. Clinical events within 14 days of randomization were recorded: recurrent ischemic stroke, symptomatic intracranial hemorrhage, death resulting from presumed cerebral edema, fatal coronary heart disease, and death. Survival and dependency were assessed at 6 months. Outcomes were adjusted for age, sex, clinical stroke syndrome, time to randomization, consciousness level, atrial fibrillation, and treatment allocation (aspirin, unfractionated heparin, both, or neither). A U-shaped relationship was found between baseline SBP and both early death and late death or dependency: early death increased by 17.9% for every 10 mm Hg below 150 mm Hg (P<0.0001) and by 3.8% for every 10 mm Hg above 150 mm Hg (P=0.016). The rate of recurrent ischemic stroke within 14 days increased by 4.2% for every 10-mm Hg increase in SBP (P=0.023); this association was present in both fatal and nonfatal recurrence. Death resulting from presumed cerebral edema was independently associated with high SBP (P=0.004). No relationship between symptomatic intracranial hemorrhage and SBP was seen. Low SBP was associated with a severe clinical stroke (total anterior circulation syndrome) and an excess of deaths from coronary heart disease (P=0.002). Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome, relationships that appear to be mediated in part by increased rates of early recurrence and death resulting from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure. The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP.
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            Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk.

            We investigated whether reduced cardiovascular risk is more related to the progressive decrease of asleep or awake blood pressure. Independent studies have concluded that elevated sleep-time blood pressure is a better predictor of cardiovascular risk than awake or 24-h blood pressure means. However, the impact on cardiovascular risk of changes in these ambulatory blood pressure characteristics has not been properly investigated. We prospectively studied 3,344 subjects (1,718 men and 1,626 women), 52.6 ± 14.5 years of age, during a median follow-up of 5.6 years. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. Blood pressure was measured for 48 h at baseline and again annually or more frequently (quarterly) if treatment adjustment was required. With data collected at baseline, when asleep blood pressure was adjusted by awake mean, only the former was a significant predictor of outcome in a Cox proportional hazards model also adjusted for sex, age, and diabetes. Analyses of changes in ambulatory blood pressure during follow-up revealed a 17% reduction in cardiovascular risk for each 5-mm Hg decrease in asleep systolic blood pressure mean (p < 0.001), independently of changes in any other ambulatory blood pressure parameter. The sleep-time blood pressure mean is the most significant prognostic marker of cardiovascular morbidity and mortality. Most importantly, the progressive decrease in asleep blood pressure, a novel therapeutic target that requires proper patient evaluation by ambulatory monitoring, was the most significant predictor of event-free survival. (Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk [the MAPEC Study]; NCT00295542). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Measuring inconsistency in meta-analyses


                Author and article information

                J Am Heart Assoc
                J Am Heart Assoc
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                01 June 2020
                16 June 2020
                : 9
                : 12 ( doiID: 10.1002/jah3.v9.12 )
                [ 1 ] Division of Neurology Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Bangkok Thailand
                [ 2 ] King Chulalongkorn Memorial Hospital Thai Red Cross Society Bangkok Thailand
                [ 3 ] Department of Medicine University of Mississippi Medical Center Jackson MS
                [ 4 ] Division of Nephrology Department of Medicine Mayo Clinic Rochester MN
                [ 5 ] Department of Cardiovascular Medicine Mayo Clinic Rochester MN
                [ 6 ] Department of Internal Medicine University of Arizona Tucson AZ
                [ 7 ] Department of Internal Medicine Mayo Clinic Jacksonville FL
                [ 8 ] University Hospitals Birmingham NHS Foundation Trust Birmingham United Kingdom
                [ 9 ] Department of Medicine Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Bangkok Thailand
                Author notes
                [* ]Correspondence to: Ronpichai Chokesuwattanaskul, MD, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. E‐mail: drronpichaic@ 123456gmail.com
                © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 3, Tables: 1, Pages: 17, Words: 5781
                Systematic Review and Meta‐analysis
                Systematic Review and Meta‐analysis
                Custom metadata
                16 June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:19.07.2020


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