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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.)

In this large-scale prospective cohort study, a propensity score matching method was applied in a natural experimental design to investigate how post-acute care (PAC) after stroke affects functional status and to identify predictors of functional status. The main objective of this study was to examine longitudinal changes in various measures of functional status in stroke patients and predictors of scores for these measures before and after PAC. A group of patients who had received PAC for stroke at one of two medical centers (PAC group, n = 273) was compared with a group who had received standard care for stroke at one of four hospitals (three regional hospital and one district hospital; non-PAC group, n = 273) in Taiwan from March, 2014, to October, 2018. The patients completed the functional status measures before rehabilitation, the 12th week and the 1st year after rehabilitation. Generalized estimating equations were used to estimate differences-in-differences models for examining the effects of PAC. The average age was 68.0 (SD = 8.1) years, and males accounted for 57.9%. During the follow-up period, significant risk factors for poor functional outcomes were advanced age, hemorrhagic stroke, and poor function scores before rehabilitation ( p < 0.05). Between-group comparisons at subsequent time points revealed significantly higher functional status scores in the PAC group versus the non-PAC group ( p < 0.001). Notably, for all functional status measures, between-group differences in total scores significantly increased over time from baseline to 1 year post-rehabilitation ( p < 0.001). The contribution of this study is its further elucidation of the clinical implications and health policy implications of rehabilitative care after stroke. Specifically, it improves understanding of the effects of PAC in stroke patients at different follow-up times. Therefore, a policy implication of this study is that standard care for stroke should include intensive rehabilitative PAC to maximize recovery of overall function.

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.)

Objective: To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI) in Mandarin-speaking subjects and to investigate the clinical application of the shortest form., Methods: Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC) analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening., Results: Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control group in the three neuropsychological protocols. Forty-two patients with stroke were diagnosed with VCI. VCI was used as the standard to estimate the criteria validities. The area under the ROC curve was 0.78, 0.80, 0.75, and 0.73 for the 60-, 30-, 5-mintue protocol-A and 5-minute protocol-B, respectively., Conclusion: These modified neuropsychological protocols can be used as valid instruments when performing comprehensive cognitive assessment or for screening of VCI in Taiwan.

Background: Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα). Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients., Methods: The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted., Results: The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011), but not in men (adjusted p = 0.300)., Conclusions: Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

Background and Purpose: Parental stroke is a risk factor for stroke among the offspring. Carotid artery intima-media thickness (IMT) is a widely regarded surrogate marker for atherosclerosis and a predictive marker for stroke. This study examines whether parental stroke is associated with IMT progression., Methods: This longitudinal study had two measures of IMT that were taken upon enrollment of the 521 subjects and after an average follow-up of 4.1 years. The rate of IMT progression was tested for associations with parental stroke and cardiovascular risk factors using ANCOVA models. Age and sex were also tested as effect modifiers. The subjects were allocated into the young or old group using the age of 55 years., Results: Parental history of stroke was significantly associated with progression of common carotid artery (CCA) IMT compared with no parental stroke history (13.52 vs. 10.43 μm/year, adjusted p = 0.035). The parental effect on IMT progression of the bifurcation and internal carotid artery was dependent on age group. Young subjects had faster progression, whereas older subjects with parental stroke had slower progression. There was a three-way interaction among sex, age, and parental stroke in CCA IMT progression, such that young women with parental stroke had a 69.7% faster progression than young women without parental stroke (15.58 vs. 9.18 μm/year). However, this difference was not found in young men or old subjects with and without parental stroke., Conclusions: Parental stroke is associated with carotid artery IMT progression and is more obvious in the young, especially among women. The results emphasize the clinical significance of parental stroke risk on atherosclerosis in young women., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The level of global DNA methylation may be related to the cerebrovascular disease. The methylation level of Long Interspersed Nucleotide Element 1 (LINE-1) can represent the global methylation level. We investigated the association between the methylation levels of LINE-1 and ischemic stroke in Chinese. Two hundred and eighty patients of ischemic stroke and 280 age- and sex-matched controls were enrolled. The mean percentage of three CpG sites of LINE-1 was calculated for each subject and was used for analysis. Twenty four samples were re-checked for reproducibility of the methylation assay. Multivariate regression model was used to estimate the odds ratio of stroke risk for one percent change of methylation. Sex-specific analysis was also conducted. Thirty-two cases and 11 controls did not pass the methylation assay criteria, and were excluded from further analysis. The intra-class correlation has a coefficient of 0.97 for the methylation assay. The stroke cases had a lower methylation level than controls (p=0.002), especially male subjects (p=0.001). Sex-specific analysis showed that a decrease of 1% methylation level in men could increase a stroke risk by 1.2-fold after adjusting for other risk factors. LINE-1 methylation levels did not have a significant association with stroke in women. The present study shows that a lower level of LINE-1 methylation was associated with a higher risk for ischemic stroke in men, but methylation level in women did not affect the stroke risk. Our finding in Chinese is consistent with a previous result based on elderly white men.

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.)

Autonomic cardiac dysfunction is a common complication after acute ischemic stroke (IS). We recruited 75 patients with acute IS with measurements of autonomic cardiac function, including heart rate variability (HRV) and associated parameters, and compared them with 81 controls. Of the 75 patients, 28 had right hemispheric infarctions (RH), 29 had left hemispheric infarctions (LH), and 18 had brainstem infarctions (BS). A comparison of HRV in all patients with stroke and in control subjects showed significant differences between IS subgroups and controls in low frequency (LF), high frequency (HF), normalized LF, normalized HF, and LF/HF ranges. A post-hoc comparison identified significant differences between patients with IS with BS infarctions and the control group in LF, HF, and LF/HF ranges. BS infarction may cause a much greater increase in sympathetic modulation and reduced vagal activity compared to RH or LH infarction. Our findings provide evidence that acute IS causes significant damage to the cardiovascular autonomic system, manifesting as abnormalities of HRV. BS stroke might correlate with a significant reduction in parasympathetic and an increase in sympathetic influence on HRV., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population., Methods: A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point), age- and sex-comparable controls, plaque-free controls, and stroke subtypes., Results: We did not find any significant association for the entire data set (OR = 0.94, p = 0.74) or for the subset analyses using age- and sex-comparable controls (p = 0.70) and plaque-free controls (p = 0.91). Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 - 0.98). For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects). Comparing stroke cases with plaque-free controls also failed to find any significant association., Conclusions: The BRAP polymorphism may not play an important role in ischemic stroke in the studied population.

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.)

Background: Genetic variants on chromosome 9p21 confer a robust risk for coronary artery disease but inconsistent risk for stroke. This study investigated whether such genetic variants exert differential risks on myocardial infarction (MI) and ischemic stroke in a Taiwanese population., Methods: The study recruited 425 MI patients, 687 patients with ischemic stroke, and 1377 healthy controls. Four key single nucleotide polymorphisms (SNPs) on chromosome 9p21 were genotyped., Results: Multivariate permutation analyses demonstrated that the risk T allele of rs1333040 and G allele of rs2383207 were associated with MI (P = 0.045 and 0.002, respectively). Subjects with the rs2383207 GG genotype had a 1.85-fold (P = 0.021) risk for MI when compared with the subjects with the AA genotype. Further analysis showed that significant results only exist in the young MI group (<65 years) but not in the old MI group (≥65 years). These SNPs were not statistically significant for stroke (adjusted P ranged from 0.097 to 0.540). Haplotype analysis showed global P values of 0.032 for MI and 0.290 for stroke., Conclusions: Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs.

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: Growing evidence suggests that white matter hyperintensities (WMHs) are implicated in stroke recurrence and mortality, and their location can be a critical factor. This study evaluated the impact of periventricular WMHs (PVWMHs) and subcortical WMHs (SWMHs) on poststroke functional outcomes., Methods: Brain MRI was performed on 187 acute ischemic stroke patients (57.8% male; mean age = 64.3 years) recruited from the Kaohsiung Municipal Hsiao-Kang Hospital from February 2007 to January 2008. A Fazekas score >or=2 in the periventrcular or subcortical white matter was taken as presence of WMHs. Demographic data and risk factors for stroke were assessed. Functional stroke outcomes were evaluated 30 days after stroke using the Barthel Index (BI) and the modifiedRankin Scale (mRS)., Results: WMHs were inversely linked to favorable functional outcome measured by mRS (p = 0.001) and BI (p = 0.003). Evaluating different locations, PVWMHs were associated with unfavorable functional outcomes (p = 0.002, mRS; p = 0.001, BI). SWMHs were related to mRS (p = 0.026) but not BI (p = 0.069). After controlling other stroke risk factors, infarct volumes and initial stroke severity, PVWMHs were a significant indicator for both mRS (OR = 2.76; 95% CI = 1.03-7.40) and BI (OR = 3.07; 95% CI = 1.13-8.40), but SWMHs were not., Conclusions: Unfavorable functional stroke outcome is associated with MRI WMHs. In terms of location, PVWMHs but not SWMHs are related to functional stroke outcome.

Background and Purpose: Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes., Methods: B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS +/-1 SD., Results: We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (P=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (P=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS >or=9 had significantly increased IMT than those with GRS

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.

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. [ABSTRACT FROM AUTHOR]

Genetic variants on chromosome 9p21 confer a robust risk for coronary artery disease but inconsistent risk for stroke. This study investigated whether such genetic variants exert differential risks on myocardial infarction (MI) and ischemic stroke in a Taiwanese population.The study recruited 425 MI patients, 687 patients with ischemic stroke, and 1377 healthy controls. Four key single nucleotide polymorphisms (SNPs) on chromosome 9p21 were genotyped.Multivariate permutation analyses demonstrated that the risk T allele of rs1333040 and G allele of rs2383207 were associated with MI (P = 0.045 and 0.002, respectively). Subjects with the rs2383207 GG genotype had a 1.85-fold (P = 0.021) risk for MI when compared with the subjects with the AA genotype. Further analysis showed that significant results only exist in the young MI group (<65 years) but not in the old MI group (≥65 years). These SNPs were not statistically significant for stroke (adjusted P ranged from 0.097 to 0.540). Haplotype analysis showed global P values of 0.032 for MI and 0.290 for stroke.Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs. [ABSTRACT FROM AUTHOR]

Few papers discuss how the economic burden of patients with stroke receiving rehabilitation courses is related to post-acute care (PAC) programs. This is the first study to explore the economic burden of stroke patients receiving PAC rehabilitation and to evaluate the impact of multidisciplinary PAC programs on cost and functional status simultaneously. A total of 910 patients with stroke between March 2014 and October 2018 were separated into a PAC group (at two medical centers) and a non-PAC group (at three regional hospitals and one district hospital) by using propensity score matching (1:1). A cost–illness approach was employed to identify the cost categories for analysis in this study according to various perspectives. Total direct medical cost in the per-diem-based PAC cohort was statistically lower than that in the fee-for-service-based non-PAC cohort (p < 0.001) and annual per-patient economic burden of stroke patients receiving PAC rehabilitation is approximately US $354.3 million (in 2019, NT $30.5 = US $1). Additionally, the PAC cohort had statistical improvement in functional status vis-à-vis the non-PAC cohort and total score of each functional status before rehabilitation and was also statistically significant with its total score after one-year rehabilitation training (p < 0.001). Early stroke rehabilitation is important for restoring health, confidence, and safe-care abilities in these patients. Compared to the current stroke rehabilitation system, PAC rehabilitation shortened the waiting time for transfer to the rehabilitation ward and it was indicated as an efficient policy for treatment of stroke in saving medical cost and improving functional status. [ABSTRACT FROM AUTHOR]

Few studies have investigated the characteristics of stroke inpatients after post-acute care (PAC) rehabilitation, and few studies have applied propensity score matching (PSM) in a natural experimental design to examine the longitudinal impacts of a medical referral system on functional status. This study coupled a natural experimental design with PSM to assess the impact of a medical referral system in stroke patients and to examine the longitudinal effects of the system on functional status. The intervention was a hospital-based, function oriented, 12-week to 1-year rehabilitative PAC intervention for patients with cerebrovascular diseases. The average duration of PAC in the intra-hospital transfer group (31.52 days) was significantly shorter than that in the inter-hospital transfer group (37.1 days) (p < 0.001). The intra-hospital transfer group also had better functional outcomes. The training effect was larger in patients with moderate disability (Modified Rankin Scale, MRS = 3) and moderately severe disability (MRS = 4) compared to patients with slight disability (MRS = 2). Intensive post-stroke rehabilitative care delivered by per-diem payment is effective in terms of improving functional status. To construct a vertically integrated medical system, strengthening the qualified local hospitals with PAC wards, accelerating the inter-hospital transfer, and offering sufficient intensive rehabilitative PAC days are the most essential requirements. [ABSTRACT FROM AUTHOR]