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Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBP max (p = 0.0426), SBP SV (p = 0.0006), DBP max-min (p = 0.0437), DBP SV (p = 0.0358), DBP SD (p = 0.0393), PP max-min (p = 0.0478), PP SV (p < 0.0001), PP SD (p = 0.0034), and PP CV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events., Methods: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk., Results: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD 2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke., Conclusions: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke., (Copyright © 2017 American Federation for Medical Research.)

Vertigo can be a major presentation of posterior circulation stroke and can be easily misdiagnosed because of its complicated presentation. We thus prospectively assessed the predictive value of vertebral artery extracranial color-coded duplex sonography (ECCS) for the prediction of ischemic stroke-related vertigo. The inclusion criteria were: (1) a sensation of whirling (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate treatment; and (3) those who could complete cranial magnetic resonance imaging (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive participants with vertigo were enrolled from Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed. We chose the parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index (PI) to represent the hemodynamics. Values from both sides of V2 segments were averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV (aPSV)/EDV, and average (aMV). Axial and coronal diffusion-weighted MRI findings determined the existence of acute ischemic stroke. We grouped and analyzed participants in two ways (way I and way II analyses) based on the diffusion-weighted MRI findings (to determine whether there was acute stroke) and neurological examinations. Using way I analysis, the "MRI (+)" group had significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the "MRI (-)" group. The cutoff value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) and MRI (-) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0 (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066), 0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0.0068), respectively. Using way II analysis, lower aEDV and aMV, and higher aRI, aPI, and aPSV/EDV ratio could determine the "MRI (+) without focal signs" group. The cutoff value/sensitivity/specificity of aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) without focal signs and MRI (-) groups were 9.10/71.4/96.0 (p = 0.0005), 15.65/57.1/96.0 (p = 0.0124), 1.10/100/70.0 (p = 0.0002), 0.64/100/70.0 (p = 0.0023), and 2.80/100/70.0 (p = 0.0017), respectively. In conclusion, using demographic data and clinical symptoms, it was difficult to determine the patients with ischemic stroke-related vertigo. Although neurological examinations still have diagnostic value, the high impedance and low velocity pattern of V2 ECCS can be an add-on method for the screening of acute ischemic stroke-related vertigo, even for those without focal neurological signs., (Copyright © 2013. Published by Elsevier B.V.)

Objective: Single nucleotide polymorphisms (SNPs) located at microRNA (miRNA) binding sites (miR-SNPs) can affect the expression of genes. This study aimed to identify the miR-SNPs associated with atherosclerosis and stroke., Methods: Patients with ischemic stroke (n = 657) and stroke- and myocardial infarction-free volunteers (n = 1571) were enrolled. The carotid intima-media thickness (IMT) was measured in the control participants. Seventy-nine stroke susceptibility genes were initially selected and 13 genes were predicted to have miR-SNPs at their 3' untranslated regions (3'UTR). The miRNA arrays were used to further identify potential miR-SNPs. The miR-SNP rs3735590 at the paraoxonase 1 (PON1) gene was finally selected and its associations with stroke and carotid IMT were evaluated. The 3'UTR reporter and SNP functional assays were then performed to validate the results., Results: Compared with CC genotype, patients with CT or TT genotype at rs3735590 had lower risk of ischemic stroke (OR = 0.72, p = 0.036; OR = 0.83, p = 0.077, respectively). Among the healthy participants, the CT or TT genotype was associated with thinner IMT in the internal carotid arteries in comparison with CC genotype (β = -0.76, p = 0.003; β = -0.022, p = 0.452, respectively). Our findings suggested that the minor allele T had a protective effect on atherosclerosis. Results from 3'UTR reporter assays showed that PON1 is a direct target gene of miR-616. In plasmid constructs carrying the risk allele C at rs3735590, miR-616 inhibited the genetic expression of PON1. However, substitution of C by T at rs3735590 reduced the miR-616 binding affinity, leading to overexpression of the PON1 gene., Conclusion: Our study is the first to show that the miR-SNP at PON1 could affect genetic expression and is associated with an elevated risk for ischemic stroke and subclinical atherosclerosis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: MicroRNA miR-21, miR-221 and miR-145 have been implicated in the cardiovascular system. We aimed to compare the serum levels of the three microRNAs (miRNAs) in different severities of cerebrovascular diseases and evaluate the feasibility of using these miRNAs as biomarkers for stroke., Methods: We enrolled 167 subjects with ischemic stroke, 66 atherosclerosis subjects with any carotid plaque score and 157 healthy controls. These three types of subjects represent three levels of severity in cerebrovascular diseases. Analysis of covariance was used to evaluate the relationship between miRNAs and disease severity with adjustment for conventional risk factors. To test the prediction for stroke, we built regression models containing the serum miRNA levels and risk factors. Prediction capabilities were compared by the receiver operating characteristic curves., Results: Stroke patients and atherosclerosis subjects had significantly higher miR-21 and lower miR-221 serum levels than healthy controls, while the miR-145 expression was too low to provide useful information in this regard. The best model showed that miR-21 and miR-221 were independent predictors. There was a 6.2-fold increase for stroke risk when miR-21 levels increase by log₁₀2(-ΔCt) = 1, while a 10.4-fold increase was observed as miR-221 decreases by log₁₀2(-ΔCt) = 1., Conclusions: Serum miR-145 was not detected in over 50% of the patients and it may not be an ideal marker to predict stroke. MiR-21 and miR-221 are novel biomarkers for atherosclerosis and stroke., (Copyright © 2013 S. Karger AG, Basel.)

Circadian variation of the onset time of acute ischemic stroke has been well studied. However, little is mentioned about the circadian variation of discharge-stroke severity and discharge-functional status. This study evaluated the impact of onset time on discharge-stroke severity and the functional status of acute ischemic stroke. Brain magnetic resonance imaging was performed on 274 acute ischemic stroke patients (66.42% male; mean age = 64.81 ± 12.80 years). All times of onset were assigned to 4-hourly periods (six groups) starting from midnight. Stroke severity/functional status was evaluated on admission and discharge using the National Institute of Health Stroke Scale (NIHSS) score/modified Rankin Scale (mRS) and Barthel Index (BI), respectively. Using mRS, but not NIHSS score and BI, it was possible to differentiate the best and worst groups on discharge. Patients in group 2 (4 to <8 am) and group 6 (8 to <12 pm) had best and worst functional status, respectively. To control other stroke risk factors, multiple logistic regression analyses were conducted to examine the role of onset time in discharge mRS. Aside from age, onset time was a significant indicator in mRS, while gender, hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and current smoking were not. In conclusion, there is also circadian variation of discharge-functional status in patients with acute ischemic stroke when assessed by mRS., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result., Materials and Methods: A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes., Results: We did not find any significant association for overall stroke (p=0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association., Conclusions: GJA4 polymorphism is not associated with stroke risk in the Taiwanese population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cardiac autonomic dysfunction is a common complication after acute ischemic stroke (IS). Prior investigators have emphasized that infarction of brain stem or hemispheres with insular involvement is related to this dysfunction and may predict poor clinical outcome. From the viewpoint of stroke physicians, however, all stroke patients, particularly large-artery atherosclerosis (LAA) should be monitored for possible cardiac complications after acute IS. This study aimed to investigate cardiac autonomic impaction in patients with acute IS and to make the comparison between LAA and small-vessel occlusion (SVO) subtypes. Of the 126 acute IS patients prospectively enrolled in this study, 32 had LAA, 56 had SVO, and 38 had undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Cardiac autonomic function of all patients was assessed by measuring heart rate variability (HRV). The low- and high-frequency components of HRV in all stroke patients were significantly lower than those of control subjects after comparing multivariable models, including additional adjustments for age, gender, and all risk factors. There were no significant differences on HRV between LAA and SVO although post hoc comparisons showed that stroke patients of SVO had increased sympathetic modulation and reduced vagal activity. In conclusion, in acute IS patients, both LAA and SVO are predisposed to have cardiac autonomic dysfunction, manifesting as abnormalities in HRV, whether in hemispheric or brain stem lesions. Stroke patients of SVO are at higher risks of cardiac abnormalities, which might suggest an early cardiac dysfunction because of long-term hypertension. The HF component of HRV thought to be for vagal control might be a cardinal marker for predicting cardiac autonomic dysfunction after acute IS. Short-term HRV spectral analysis is a convenient approach for stroke clinicians to assess autonomic function in acute stroke. Long-term follow-up for HRV and clinical outcome relative to LAA and SVO stroke subtypes is warranted, particularly when an abnormal HRV is found at admission., (Copyright © 2011. Published by Elsevier B.V.)

Background: Although there have been studies of the genetic risk factors in the development of stroke, there have been few investigations of role of genes in the cerebral response to ischemia. The brain responds to ischemia in a series of reactions that ultimately influence the volume of a stroke that, in general, correlates with disability. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of this response and impact stroke volume. One of the pathways participating in the cerebral ischemic response involves reactive oxygen species which can cause oxidative damage to nucleic acids. DNA repair mechanisms are in place to protect against such damage and imply a role for DNA repair genes in the response of the brain to ischemia and are potential candidate genes for further investigation., Methods: We studied two common polymorphisms in the DNA repair gene, XRCC1, C26304T and G28152A, in 134 well characterized patients with non lacunar ischemic strokes. We also performed a case control association study with 113 control patients to assess whether these variants represent risk factors in the development of ischemic stroke., Results: Independent of etiology, the "T" allele of the C26304T polymorphism is significantly associated with larger stroke volumes (T-test analysis, p < 0.044; multivariate regression analysis, beta = 0.23, p < 0.008). In the case control association study, we found that neither of these polymorphisms represented a risk factor for the development of stroke., Conclusion: Our study suggests a major gene effect of the "T" allele of the C26304T polymorphism modulating the cerebral response to ischemia in non lacunar ischemic stroke.