Study protocol for a systematic review and meta-analysis of comorbidities and stroke characteristics associated with troponin elevation after acute stroke

IntroductionIt is unknown which comorbidities and stroke characteristics are associated with elevated cardiac troponin (cTn) levels after stroke. The main objective of this systematic review and meta-analysis is to assess the association of elevated cTn with preexisting cardiovascular comorbidities (eg, coronary artery disease, heart failure and structural heart disease), specific stroke characteristics (eg, infarct/haemorrhage size, stroke severity, insular cortex involvement) and renal failure after ischaemic stroke (IS) or intracranial haemorrhage (ICH). The secondary objective is to evaluate the association of elevated cTn with stroke recurrence and death.Methods and analysisWe will include all cross-sectional, case–control, cohort studies and clinical trials involving IS and ICH adult patients (≥18 years), published between 1 January 1990 and 31 December 2020 in English or Spanish, reporting the proportion with elevated cTn. We will search PubMed, EMBASE and Web of Science by applying predefined search terms. Two reviewers will independently screen titles and abstracts, retrieve full texts, extract the data in a predesigned form, and assess the risk of bias. We will apply random-effects or fixed-effects meta-analyses to estimate the association between cardiovascular comorbidities, stroke characteristics and renal failure with cTn elevation. We will report results as risk ratios or ORs. We will perform sensitivity analyses for subtypes of cTn (cTn-I and cTn-T), regular versus high-sensitivity assays, and type of stroke (IS vs ICH). We will estimate heterogeneity by using t2Q and I2 measures. We will use funnel plots, Rosenthal’s Fail-Safe N, Duval and Tweedie’s trim and fill procedure, and Egger’s regression intercept to assess publication bias.Ethics and disseminationThis review will be based on published data and does therefore not require ethical clearance. The results will be published in peer-reviewed journals.PROSPERO registration numberCRD42020203126.

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Knowledge of blood donation and associated factors in Ethiopia: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-044343 ◽

2021 ◽

Vol 11 (7) ◽

pp. e044343

Author(s):

Addisu Getie ◽

Adam Wondmieneh ◽

Melaku Bimerew ◽

Getnet Gedefaw ◽

Asmamaw Demis

Keyword(s):

Systematic Review ◽

Associated Factors ◽

Blood Donation ◽

Meta Analysis ◽

Educational Status ◽

Sensitivity Analyses ◽

Cross Sectional ◽

Level Of Knowledge ◽

Cross Sectional Studies ◽

Study Participants

ObjectiveTo assess the level of knowledge about blood donation and associated factors in Ethiopia.DesignSystematic review and meta-analysis.MethodsBoth published and unpublished cross-sectional studies on the level of knowledge about blood donation in Ethiopia were included. Articles from different databases such as PubMed/MEDLINE, HINARI, EMBASE, Scopus, Google Scholar and African Journals Online were searched. Cochrane I2 statistics were used to check for heterogeneity. Subgroup and sensitivity analyses of evidence of heterogeneity were carried out. Egger’s test with funnel plot was conducted to investigate publication bias.ResultTwenty cross-sectional studies with a total of 8338 study participants (4712 men and 3626 women) were included. The overall nationwide level of knowledge about blood donation was 56.57% (95% CI 50.30 to 62.84). Being in secondary school and above (adjusted OR=3.12; 95% CI 2.34 to 4.16) and being male (adjusted OR=1.81; 95% CI 1.44 to 2.28) were the factors associated with level of knowledge about blood donation.ConclusionMore than half of the study participants were knowledgeable about blood donation. Sex and educational status were the factors significantly associated with level of knowledge about blood donation in Ethiopia. Therefore, there is a need for education and dissemination of information about blood donation among the general population to build adequate knowledge and maintain regular blood supply.

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Total Dairy, Cheese and Milk Intake and Arterial Stiffness: A Systematic Review and Meta-Analysis of Cross-sectional Studies.

Nutrients ◽

10.3390/nu11040741 ◽

2019 ◽

Vol 11 (4) ◽

pp. 741 ◽

Cited By ~ 8

Author(s):

Ana Diez-Fernández ◽

Celia Álvarez-Bueno ◽

Vicente Martínez-Vizcaíno ◽

Mercedes Sotos-Prieto ◽

José Recio-Rodríguez ◽

...

Keyword(s):

Systematic Review ◽

Arterial Stiffness ◽

Dairy Products ◽

Fixed Effects ◽

Meta Analysis ◽

Dairy Product ◽

Milk Intake ◽

Cross Sectional ◽

Product Consumption ◽

Dairy Product Consumption

The aim of this review was to determine the relationship between dairy product consumption and arterial stiffness, measured by pulse wave velocity (PWV). We systematically searched the Medline, Embase and Web of Science databases until 30th January 2019 for cross-sectional data from studies addressing the association between dairy product consumption and PWV. This study was registered with PROSPERO (CRD42018110528). Both the inverse-variance fixed effects method and the DerSimonian and Laird method were used to compute pooled estimates of effect size (ES) and the respective 95% confidence intervals (CIs). Seven studies were included in the meta-analysis, with a total of 16,443 patients. Total dairy product (ES = −0.03; 95% CI [−0.04, −0.01]) and cheese (ES = −0.04; 95% CI [−0.07, −0.01]) consumption were weak, but significantly associated with lower PWV levels. Conversely, milk intake showed no significant association with PWV (ES = 0.02; 95% CI [−0.01, 0.05]). Heterogeneity in the ES was not important for the three groups of dairy products assessed. This systematic review and meta-analysis of seven studies found no detrimental effects of dairy product consumption on arterial stiffness measured by PWV. Due to the scarcity of studies, further investigations are warranted to clarify the role of dairy products on arterial stiffness.

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Parathyroid hormone analogues for fracture healing: protocol for a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2017-019291 ◽

2018 ◽

Vol 8 (1) ◽

pp. e019291 ◽

Cited By ~ 5

Author(s):

Shenghan Lou ◽

Houchen Lv ◽

Zhirui Li ◽

Peifu Tang ◽

Yansong Wang

Keyword(s):

Systematic Review ◽

Parathyroid Hormone ◽

Fracture Healing ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Published Data ◽

Controlled Trials ◽

Anabolic Effect ◽

Randomised Controlled

IntroductionFracture healing is a complex physiological process. Impaired healing will increase the need for care and cause serious complications. Thus, identifying strategies to accelerate the rate of healing, preventing delayed unions and non-unions, is essential. Parathyroid hormone (PTH) is a key systemic regulator of calcium and phosphate metabolism. It has been determined that intermittent administration of PTH and its analogue can exert anabolic effect on bone, increase bone mass and reduce bone loss, leading to an increase in bone formation. Owing to their anabolic effect, there is an increasing interest in its potential in promoting the process of fracture healing. However, in clinical studies, the results are in conflict. This objective of this study is to determine the role of PTH analogues for fracture healing in adults.Methods and analysisMEDLINE, EMBASE and Cochrane databases will be searched to identify all randomised controlled trials (RCTs) and quasi-RCTs that compare the different effects between PTH analogues and any other treatments in adults with any type of fracture. The primary outcome is the functional recovery. And the secondary outcomes are fracture union and adverse events. The meta-analysis will be performed using a random effects model. Heterogeneity will be assessed by the P values and I² statistic. And subgroup analyses and sensitivity analyses will be used to explore the heterogeneity. Risk of bias will be assessed using the Cochrane tool and the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not required because this proposed systematic review and meta-analysis is based on published data, without including confidential personal data or data on interventions on patients. The findings of this study will be published in a peer-reviewed journaland presented at a relevant conference.PROSPERO registration numberCRD42017062093.

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Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis

Heart ◽

10.1136/heartjnl-2020-317062 ◽

2020 ◽

Vol 106 (15) ◽

pp. 1142-1147 ◽

Cited By ~ 25

Author(s):

Xintao Li ◽

Bo Guan ◽

Tong Su ◽

Wei Liu ◽

Mengyao Chen ◽

...

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Hospital Mortality ◽

Mortality Risk ◽

Meta Analysis ◽

Cardiac Injury ◽

Sensitivity Analyses ◽

Future Research ◽

Cardiovascular Comorbidities ◽

The Impact

BackgroundCoronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk.MethodsPubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity.ResultsA total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I2=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I2=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I2=71%).ConclusionCOVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

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Prevalence of Diabetes Mellitus and Its Associated Unfavorable Outcomes in Patients With Acute Respiratory Syndromes Due to Coronaviruses Infection: A Systematic Review and Meta-Analysis

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/1179551420962495 ◽

2020 ◽

Vol 13 ◽

pp. 117955142096249

Author(s):

Isabel Pinedo-Torres ◽

Magaly Flores-Fernández ◽

Marlon Yovera-Aldana ◽

Claudia Gutierrez-Ortiz ◽

Paolo Zegarra-Lizana ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Health Outcomes ◽

Meta Analysis ◽

Population Based ◽

Pooled Analysis ◽

Sensitivity Analyses ◽

Cross Sectional ◽

Treatment Regimens ◽

Prevalence Of Diabetes Mellitus

Introduction: Only 3 types of coronavirus cause aggressive respiratory disease in humans (MERS-Cov, SARS-Cov-1, and SARS-Cov-2). It has been reported higher infection rates and severe manifestations (ICU admission, need for mechanical ventilation, and death) in patients with comorbidities such as diabetes mellitus (DM). For this reason, this study aimed to determine the prevalence of diabetes comorbidity and its associated unfavorable health outcomes in patients with acute respiratory syndromes for coronavirus disease according to virus types. Methods: Systematic review of literature in Pubmed/Medline, Scopus, Web of Science, Cochrane, and Scielo until April of 2020. We included cohort and cross-sectional studies with no restriction by language or geographical zone. The selection and extraction were undertaken by 2 reviewers, independently. The study quality was evaluated with Loney’s instrument and data were synthesized by random effects model meta-analysis. The heterogeneity was quantified using an I2 statistic. Funnel plot, Egger, and Begg tests were used to evaluate publication biases, and subgroups and sensitivity analyses were performed. Finally, we used the GRADE approach to assess the evidence certainty (PROSPERO: CRD42020178049). Results: We conducted the pooled analysis of 28 studies (n = 5960). The prevalence analysis according to virus type were 451.9 diabetes cases per 1000 infected patients (95% CI: 356.74-548.78; I2 = 89.71%) in MERS-Cov; 90.38 per 1000 (95% CI: 67.17-118.38) in SARS-Cov-1; and 100.42 per 1000 (95% CI: 77.85, 125.26 I2 = 67.94%) in SARS-Cov-2. The mortality rate were 36%, 6%, 10% and for MERS-Cov, SARS-Cov-1, and SARS-Cov-2, respectively. Due to the high risk of bias (75% of studies had very low quality), high heterogeneity ( I2 higher than 60%), and publication bias (for MERS-Cov studies), we down rate the certainty to very low. Conclusion: The prevalence of DM in patients with acute respiratory syndrome due to coronaviruses is high, predominantly with MERS-Cov infection. The unfavorable health outcomes are frequent in this subset of patients. Well-powered and population-based studies are needed, including detailed DM clinical profile (such as glycemic control, DM complications, and treatment regimens), comorbidities, and SARS-Cov-2 evolution to reevaluate the worldwide prevalence of this comorbidity and to typify clinical phenotypes with differential risk within the subpopulation of DM patients.

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Do early life “non-cognitive skills” matter? A systematic review and meta-analysis of early life effects on academic achievement, psychosocial, language and cognitive, and health outcomes

10.1101/115691 ◽

2017 ◽

Cited By ~ 1

Author(s):

Lisa G. Smithers ◽

Alyssa C. P. Sawyer ◽

Catherine R. Chittleborough ◽

Neil Davies ◽

George Davey Smith ◽

...

Keyword(s):

Systematic Review ◽

Academic Achievement ◽

Study Design ◽

Early Life ◽

Cognitive Skills ◽

Fixed Effects ◽

Meta Analysis ◽

Self Regulation ◽

Sample Type ◽

Cross Sectional

AbstractBackgroundSuccess in school and the labour market is due to more than just high intelligence. Associations between traits such as attention, self-regulation, and perseverance in childhood, and later outcomes have been investigated by psychologists, economists, and epidemiologists. Such traits have been loosely referred to as “non-cognitive” skills. There has been no attempt to systematically assess the relative importance of non-cognitive skills in early life on later outcomes.MethodsThe systematic review protocol was registered with the International Prospective Register for Systematic Reviews (PROSPERO, CRD42013006566) in December 2013. We systematically reviewed electronic databases covering psychology, education, health and economics for articles published from database conception until September 2015. Titles and abstracts were screened for eligibility, and from eligible articles data was extracted on study design, sample type and size, age of participants at exposure and outcome, loss to follow up, measurement of exposure and outcome, type of intervention and comparison group, confounding adjustment and results. Where possible we extracted a standardised effect size. We reviewed all studies and rated their evidence quality as ‘better, weak, or poor’ on the basis of study design and potential for confounding, selection and measurement bias.ResultsWe reviewed 375 studies and provided interpretation of results from 142 (38%) better quality studies comprising randomised controlled trials, quasi-experimental, fixed effects including twin studies, longitudinal and some cross-sectional designs that made reasonable attempts to control confounding. In the academic achievement category outcomes were reported in 78 publications of better quality studies which were consistent with 0.1-0.2 SD effects.Psychosocial outcomes were reported in 65 better quality studies consistent with effects of 0.3-0.4 SD. For the language and cognitive category there were 42 publications reporting better quality studies consistent with effects of 0.3-0.4 SD. For physical health, results across only eight better quality studies were inconsistent but centred around zero. Analysis of funnel plots consistently showed asymmetric distributions, raising the potential of small study bias which may inflate these observed effects.ConclusionsThe evidence under-pinning the importance of non-cognitive skills for life success is diverse and inconsistent. Nevertheless, there is tentative evidence from published studies that non-cognitive skills associate with modest improvements in academic achievement, psychosocial, and language and cognitive outcomes with effects in the range of 0.2-0.4 SD. The quality of evidence under-pinning this field is generally low with more than a third of studies making little or no attempt to control even the most basic confounding (endogeneity) bias. The evidence could be improved by adequately powering studies, and using procedures and tools that improve the conduct and reporting of RCTs and observational studies. Interventions designed to develop children’s non-cognitive skills could potentially improve opportunities, particularly for disadvantaged children. The inter-disciplinary researchers interested in these skills should take a more rigorous approach to determine which interventions are most effective.

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Cardiovascular manifestations in COVID-19 patients: A systematic review and meta-analysis

Journal of Cardiovascular and Thoracic Research ◽

10.34172/jcvtr.2021.30 ◽

2021 ◽

Vol 13 (3) ◽

pp. 181-189

Author(s):

Seyyedmohammadsadeq Mirmoeeni ◽

Amirhossein Azari Jafari ◽

Seyedeh Zohreh Hashemi ◽

Elham Angouraj Taghavi ◽

Alireza Azani ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Systolic Pressure ◽

Clinical Manifestations ◽

Laboratory Findings ◽

Cross Sectional ◽

Cardiovascular Comorbidities ◽

Study Characteristics ◽

Novel Coronavirus ◽

Cardiac Manifestations

Since December 2019, the COVID-19 pandemic has affected the global population, and one of the major causes of mortality in infected patients is cardiovascular diseases (CVDs).For this systematic review and meta-analysis, we systematically searched Google Scholar, Scopus, PubMed, Web of Science, and Cochrane databases for all articles published by April 2, 2020. Observational studies (cohort and cross-sectional designs) were included in this meta-analysis if they reported at least one of the related cardiovascular symptoms or laboratory findings in COVID-19 patients. Furthermore, we did not use any language, age, diagnostic COVID-19 criteria, and hospitalization criteria restrictions. The following keywords alone or in combination with OR and AND operators were used for searching the literature: "Wuhan coronavirus", "COVID-19", "coronavirus disease 2019", "SARS-CoV-2", "2019 novel coronavirus" "cardiovascular disease", "CVD", "hypertension", "systolic pressure", "dyspnea", "hemoptysis", and "arrhythmia". Study characteristics, exposure history, laboratory findings, clinical manifestations, and comorbidities were extracted from the retrieved articles. Sixteen studies were selected which involved 4754 patients, including 2103 female and 2639 male patients. Among clinical cardiac manifestations, chest pain and arrhythmia were found to have the highest incidence proportion. In addition, elevated lactate dehydrogenase (LDH) and D-dimer levels were the most common cardiovascular laboratory findings. Finally, hypertension, chronic heart failure, and coronary heart disease were the most frequently reported comorbidities. The findings suggest that COVID-19 can cause various cardiovascular symptoms and laboratory findings. It is also worth noting that cardiovascular comorbidities like hypertension have a notable prevalence among COVID-19 patients.

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Comorbid Major Depressive Disorder in Schizophrenia: A Systematic Review and Meta-Analysis

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa153 ◽

2020 ◽

Author(s):

Damien Etchecopar-Etchart ◽

Theo Korchia ◽

Anderson Loundou ◽

Pierre-Michel Llorca ◽

Pascal Auquier ◽

...

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Meta Analysis ◽

Assessment Tools ◽

Sensitivity Analyses ◽

Published Data ◽

Structured Interviews ◽

Major Depressive ◽

Antidepressant Use

Abstract Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized scale or with structured interviews were included. The Medline, Web of Science, PsycINFO, and Google Scholar databases were searched. Using random effects models, we calculated the pooled estimate of the prevalence of SZ-MDD. We used meta-regression and subgroup analyses to evaluate the potential moderators of the prevalence estimates, and we used the leave-one-out method for sensitivity analyses. Of the 5633 potentially eligible studies identified, 18 studies (n = 6140 SZ stabilized outpatients) were retrieved in the systematic review and included in the meta-analysis. The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9–37.6); there was high heterogeneity (I2 = 92.6%), and Egger’s test did not reveal publication bias (P = .122). The following factors were found to be sources of heterogeneity: publication in or after 2015, the inclusion of patients from larger studies, the assessment tools, the inclusion of patients with substance use disorder or somatic chronic diseases, age, education level, the lifetime number of hospitalizations, and antidepressant use. Two-thirds of the extracted variables could not be explored due to an insufficient amount of published data. The prevalence of MDD is high among SZ individuals. Healthcare providers and public health officials should have an increased awareness of the burden of SZ-MDD.

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Systemic lupus erythematosus; stroke and myocardial infarction risk: a systematic review and meta-analysis

RMD Open ◽

10.1136/rmdopen-2020-001247 ◽

2020 ◽

Vol 6 (2) ◽

pp. e001247

Author(s):

Jinoos Yazdany ◽

Nick Pooley ◽

Julia Langham ◽

Lindsay Nicholson ◽

Sue Langham ◽

...

Keyword(s):

Myocardial Infarction ◽

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Adult Patients ◽

Sensitivity Analyses ◽

Future Research ◽

Systemic Lupus ◽

Cross Sectional

ObjectiveTo evaluate the risk of stroke and myocardial infarction (MI) in adult patients with systemic lupus erythematosus (SLE) through a systematic review and meta-analysis.MethodsWe searched MEDLINE and EMBASE from inception to May 2020 to identify observational studies (cohort and cross-sectional) that evaluated risk of stroke and MI in adult patients with SLE compared with the general population or healthy controls. Studies were included if they reported effect-size estimates that could be used for calculating pooled-effect estimates. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% CIs for stroke and MI. Heterogeneity quantified by the I2 test and sensitivity analyses assessed bias.ResultsIn total, 26 studies were included in this meta-analysis: 14, 5 and 7 studies on stroke, MI and both stroke and MI, respectively. The pooled RR for ischaemic stroke was 2.18 (95% CI 1.78 to 2.67; I2 75%), intracerebral haemorrhage 1.84 (95% CI 1.16 to 2.90; I2 67%), subarachnoid haemorrhage 1.95 (95% CI 0.69 to 5.52; I2 94%), composite stroke 2.13 (95% CI 1.73 to 2.61; I2 88%) and MI 2.99 (95% CI 2.34 to 3.82; I2 85%). There was no evidence for publication bias, and sensitivity analyses confirmed the robustness of the results.ConclusionsOverall, patients with SLE were identified to have a twofold to threefold higher risk of stroke and MI. Future research on the interaction between known SLE-specific modifiable risk factors and risk of stroke and MI to support development of prevention and treatment strategies are needed.PROSPERO registration numberCRD42018098690.

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WMH and long-term outcomes in ischemic stroke

Neurology ◽

10.1212/wnl.0000000000007142 ◽

2019 ◽

Vol 92 (12) ◽

pp. e1298-e1308 ◽

Cited By ~ 24

Author(s):

Marios K. Georgakis ◽

Marco Duering ◽

Joanna M. Wardlaw ◽

Martin Dichgans

Keyword(s):

Ischemic Stroke ◽

Functional Impairment ◽

Recurrent Stroke ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Stroke Recurrence ◽

Stroke Severity ◽

Stroke Patients ◽

Increased Risk

ObjectiveTo investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality.MethodsFollowing the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models.ResultsWe included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias.ConclusionsPresence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.

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