Dataset Information

Association Between Endothelial Cell Stabilizing Medication and Small Vessel Disease Stroke: A Case-Control Study.

ABSTRACT: Increasing evidence suggests a role for endothelial cell (EC) dysfunction in pathogenesis of cerebral small vessel disease. Commonly used medications including certain antihypertensives and statins have EC-stabilizing effects. We used individual patient data from completed acute stroke trials to assess whether prior exposure to EC-stabilizing medications was associated with lacunar stroke, using lacunar stroke as a clinical proxy for cerebral small vessel disease. Across 12,002 patients with relevant data, 2,855 (24%) had a lacunar stroke presentation. Univariable analyses suggested potential confounding from vascular diseases treated with EC-stabilizing medications. Initial multivariable logistic regression gave conflicting results when describing the independent association of exposure to EC-stabilizing medication and lacunar stroke in the complete population (O.R. 0.87, 95% C.I.: 0.77- 0.98) and limited to those taking any antihypertensive (O.R. 1.51, 95% C.I.: 1.21-1.88). Re-running the analyses including statins in the EC-stabilizing category suggested a beneficial effect of EC-stabilizing medication exposure on lacunar stroke incidence (O.R. 0.83, 95% C.I.: 0.73-0.93). These results align with recent pre-clinical data and would support interventional trials of EC-stabilizing medication for preventing cerebral small vessel disease. Our results also suggest that analyses of EC-stabilizing interventions need to adjust for potential endothelial effects of other co-prescribed medication.

SUBMITTER: Becker CE

PROVIDER: S-EPMC6773869 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association Between Endothelial Cell Stabilizing Medication and Small Vessel Disease Stroke: A Case-Control Study.

Becker Charlotte Elisabeth CE Quinn Terence J TJ Williams Anna A

Frontiers in neurology 20190925

Increasing evidence suggests a role for endothelial cell (EC) dysfunction in pathogenesis of cerebral small vessel disease. Commonly used medications including certain antihypertensives and statins have EC-stabilizing effects. We used individual patient data from completed acute stroke trials to assess whether prior exposure to EC-stabilizing medications was associated with lacunar stroke, using lacunar stroke as a clinical proxy for cerebral small vessel disease. Across 12,002 patients with rel ...[more]

PMID: 31608006

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Project description:IntroductionAlthough pathogenesis of small vessel disease is poorly understood, increasing evidence suggests that endothelial dysfunction may have a relevant role in development and progression of small vessel disease. In this cross-sectional study, we investigated the associations between imaging signs of small vessel disease and blood biomarkers of endothelial dysfunction at two different time points in a population of ischaemic stroke patients.Patients and methodsIn stroke patients treated with intravenous thrombolysis, we analysed blood levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and vascular endothelial growth factor. Three reviewers independently assessed small vessel disease features using computed tomography. At baseline and 90 days after the index stroke, we tested the associations between single and combined small vessel disease features and levels of blood biomarkers using linear regression analysis adjusting for age, sex, hypertension, diabetes, smoke.ResultsA total of 263 patients were available for the analysis. Mean age (±SD) was 69 (±13) years, 154 (59%) patients were male. We did not find any relation between small vessel disease and endothelial dysfunction at baseline. At 90 days, leukoaraiosis was independently associated with intercellular adhesion molecule-1 (β = 0.21; p = 0.016) and vascular cell adhesion molecule-1 (β = 0.22; p = 0.009), and lacunes were associated with vascular endothelial growth factor levels (β = 0.21; p = 0.009) whereas global small vessel disease burden was associated with vascular endothelial growth factor (β = 0.26; p = 0.006).DiscussionLeukoaraiosis and lacunes were associated with endothelial dysfunction, which could play a key role in pathogenesis of small vessel disease.ConclusionsSmall vessel disease features and total burden were associated with endothelial dysfunction 90 days after the stroke, whereas there was no relation during the acute phase. Our results suggest that endothelial dysfunction, particularly vascular endothelial growth factor, is involved in pathological process of small vessel disease.

Project description:BackgroundCerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population.MethodsIn this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs.ResultsOf the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (β = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26).ConclusionsAntiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Dataset Information

Association Between Endothelial Cell Stabilizing Medication and Small Vessel Disease Stroke: A Case-Control Study.

Publications

Association Between Endothelial Cell Stabilizing Medication and Small Vessel Disease Stroke: A Case-Control Study.

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