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Journal of Atherosclerosis and... Aug 2017Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile... (Review)
Review
Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile hemodynamics in the central aorta consists of blood pressure, flow, and stiffness and substantially differs from the peripheral hemodynamics in muscular arteries. Arteriosclerotic changes with age appear earlier in the elastic aorta, and age-dependent increases in central pulse pressure are more marked than those apparent from brachial pressure measurement. Central pressure can be affected by lifestyle habits, metabolic disorders, and endocrine and inflammatory diseases in a manner different from brachial pressure. Central pulse pressure widening due to aortic stiffening increases left ventricular afterload in systole and reduces coronary artery flow in diastole, predisposing aortosclerotic patients to myocardial hypertrophy and ischemia. The widened pulse pressure is also transmitted deep into low-impedance organs such as the brain and kidney, causing microvascular damage responsible for lacunar stroke and albuminuria. In addition, aortic stiffening increases aortic blood flow reversal, which can lead to retrograde embolic stroke and renal function deterioration. Central pressure has been shown to predict cardiovascular events in most previous studies and potentially serves as a surrogate marker for intervention. Quantitative and comprehensive evaluation of central hemodynamics is now available through various noninvasive pressure/flow measurement modalities. This review will focus on the clinical usefulness and mechanistic rationale of central hemodynamic measurements for cardiovascular risk management.
Topics: Arteriosclerosis; Disease Management; Hemodynamics; Humans
PubMed: 28603219
DOI: 10.5551/jat.40717 -
Circulation. Cardiovascular Genetics Apr 2009
Review
Topics: Animals; Brain Infarction; Genetic Predisposition to Disease; Humans; Risk Factors; Stroke
PubMed: 20031584
DOI: 10.1161/CIRCGENETICS.108.828319 -
European Stroke Journal Mar 2022Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings,...
INTRODUCTION
Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke.
PATIENTS AND METHODS
We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002-2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors.
RESULTS
We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1-11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61-1.15) or MI (HR 0.83, 95% CI 0.52-1.34).
CONCLUSION
Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.
PubMed: 35287300
DOI: 10.1177/23969873211062019 -
Journal of Thrombosis and Haemostasis :... Mar 2020Mean levels of coated-platelets, a subset of highly procoagulant platelets, are decreased in patients with lacunar as compared to those with non-lacunar stroke. Elevated...
BACKGROUND
Mean levels of coated-platelets, a subset of highly procoagulant platelets, are decreased in patients with lacunar as compared to those with non-lacunar stroke. Elevated coated-platelets are associated with increased risk for recurrent infarction in non-lacunar stroke and predict incident stroke after transient ischemic attack (TIA).
OBJECTIVE
We investigated if coated-platelet levels are predictive of recurrent cerebral ischemia following lacunar stroke.
METHODS
Coated-platelet levels were assayed in consecutive patients with acute lacunar stroke, who were followed for up to 12 months. Cox proportional hazards regression analysis was used to estimate the combined risk of stroke and TIA at 12 months according to initial coated-platelet levels.
RESULTS
We enrolled a total of 109 lacunar stroke patients. Eight events were recorded over a mean follow-up period of 10.8 months. A cut-off of 42.6% for coated-platelet levels yielded a sensitivity of 0.75 (0.35-0.97; 95% confidence interval [CI]), specificity of 0.92 (0.85-0.97), positive predictive value of 0.43 (0.26-0.62), and a negative predictive value of 0.98 (0.93-0.99) for recurrent stroke/TIA. The adjusted hazard ratio for recurrent stroke/TIA in patients with coated-platelet levels ≥ 42.6% was 23.9 (95% CI: 4.26-134.4) when compared to those with levels < 42.6%.
CONCLUSIONS
Identification of increased platelet procoagulant potential may improve our ability to identify patients at higher risk of recurrent stroke/TIA following a lacunar stroke. Further study of mechanisms involved is warranted and may yield novel targets for prevention and treatment.
Topics: Blood Platelets; Humans; Ischemic Attack, Transient; Predictive Value of Tests; Recurrence; Risk Factors; Stroke; Stroke, Lacunar
PubMed: 31858724
DOI: 10.1111/jth.14714 -
Journal of the American Heart... Aug 2019See Article Agarwal et al.
See Article Agarwal et al.
Topics: Blood Pressure; Blood Pressure Determination; Humans; Secondary Prevention; Stroke; Stroke, Lacunar
PubMed: 31423888
DOI: 10.1161/JAHA.119.013637 -
Journal of Stroke and Cerebrovascular... Apr 2016Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the...
BACKGROUND
Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke.
METHODS
Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model.
RESULTS
Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61; 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71; CI = .55-.93) versus other stroke subtypes.
CONCLUSIONS
Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes.
Topics: Aged; Anxiety; Chondroitin Sulfates; Depression; Dermatan Sulfate; Female; Fibrinolytic Agents; Follow-Up Studies; Heparitin Sulfate; Humans; Male; Middle Aged; Neuroimaging; Psychiatric Status Rating Scales; Quality of Life; Stroke; Stroke, Lacunar
PubMed: 26778600
DOI: 10.1016/j.jstrokecerebrovasdis.2015.12.018 -
Annals of Neurology Sep 2011Determining which small deep infarcts (SDIs) are of lacunar, arterial, or cardioembolic etiology is challenging, but important in delivering optimal stroke prevention...
OBJECTIVE
Determining which small deep infarcts (SDIs) are of lacunar, arterial, or cardioembolic etiology is challenging, but important in delivering optimal stroke prevention therapy. We sought to distinguish lacunar from nonlacunar causes of SDIs using a gene expression profile.
METHODS
A total of 184 ischemic strokes were analyzed. Lacunar stroke was defined as a lacunar syndrome with infarction <15mm in a region supplied by penetrating arteries. RNA from blood was processed on whole genome microarrays. Genes differentially expressed between lacunar (n = 30) and nonlacunar strokes (n = 86) were identified (false discovery rate ≤ 0.05, fold change >|1.5|) and used to develop a prediction model. The model was evaluated by cross-validation and in a second test cohort (n = 36). The etiology of SDIs of unclear cause (SDIs ≥ 15mm or SDIs with potential embolic source) (n = 32) was predicted using the derived model.
RESULTS
A 41-gene profile discriminated lacunar from nonlacunar stroke with >90% sensitivity and specificity. Of the 32 SDIs of unclear cause, 15 were predicted to be lacunar, and 17 were predicted to be nonlacunar. The identified profile represents differences in immune response between lacunar and nonlacunar stroke.
INTERPRETATION
Profiles of differentially expressed genes can distinguish lacunar from nonlacunar stroke. SDIs of unclear cause were frequently predicted to be of nonlacunar etiology, suggesting that comprehensive workup of SDIs is important to identify potential cardioembolic and arterial causes. Further study is required to evaluate the gene profile in an independent cohort and determine the clinical and treatment implications of SDIs of predicted nonlacunar etiology.
Topics: Aged; Brain; Cerebral Arteries; Cerebral Infarction; Cohort Studies; Data Interpretation, Statistical; Diagnosis, Differential; Female; Gene Expression; Gene Expression Profiling; Humans; Inflammation; Intracranial Embolism; Male; Microarray Analysis; Middle Aged; Reproducibility of Results; Risk Factors; Stroke; Tomography, X-Ray Computed
PubMed: 21796664
DOI: 10.1002/ana.22497 -
Genes Sep 2022Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to... (Meta-Analysis)
Meta-Analysis
Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.
Topics: Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteoarthritis, Hip; Polymorphism, Single Nucleotide; Stroke, Lacunar
PubMed: 36140752
DOI: 10.3390/genes13091584 -
Neurology Jan 2016We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated...
OBJECTIVE
We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA).
METHODS
In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes.
RESULTS
There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07).
CONCLUSIONS
Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes.
Topics: Adult; Aged; Cerebral Infarction; Female; Genetic Variation; Genome-Wide Association Study; Humans; Leukoaraiosis; Magnetic Resonance Imaging; Male; Middle Aged; Oxidative Phosphorylation; Risk Factors; Stroke, Lacunar; Young Adult
PubMed: 26674331
DOI: 10.1212/WNL.0000000000002260 -
Clinical Science (London, England :... Oct 2017Findings from research may be less reliable where studies do not report measures to reduce risks of bias. The experimental stroke community has been at the forefront of... (Review)
Review
BACKGROUND
Findings from research may be less reliable where studies do not report measures to reduce risks of bias. The experimental stroke community has been at the forefront of implementing changes to improve reporting, but it is not known whether these efforts are associated with continuous improvements. Our aims here were firstly to validate an automated tool to assess risks of bias in published works, and secondly to assess the reporting of measures taken to reduce the risk of bias within recent literature for two experimental models of stroke.
METHODS
We developed and used text analytic approaches to automatically ascertain reporting of measures to reduce risk of bias from full-text articles describing animal experiments inducing middle cerebral artery occlusion (MCAO) or modelling lacunar stroke.
RESULTS
Compared with previous assessments, there were improvements in the reporting of measures taken to reduce risks of bias in the MCAO literature but not in the lacunar stroke literature. Accuracy of automated annotation of risk of bias in the MCAO literature was 86% (randomization), 94% (blinding) and 100% (sample size calculation); and in the lacunar stroke literature accuracy was 67% (randomization), 91% (blinding) and 96% (sample size calculation).
DISCUSSION
There remains substantial opportunity for improvement in the reporting of animal research modelling stroke, particularly in the lacunar stroke literature. Further, automated tools perform sufficiently well to identify whether studies report blinded assessment of outcome, but improvements are required in the tools to ascertain whether randomization and a sample size calculation were reported.
Topics: Animals; Bias; Brain Ischemia; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Risk; Stroke
PubMed: 29026002
DOI: 10.1042/CS20160722