Estradiol levels predict short-term adverse health outcomes in postmenopausal acute stroke women

Background: Data on the role of endogenous sex steroids in cerebrovascular disease are sparse. Estradiol is a hormone with diverse actions on the central nervous system. Our aim was to investigate the role of circulating estradiol levels in a postmenopausal acute stroke population. Methods: During a time-period of 2 years, we prospectively studied 302 postmenopausal female patients hospitalized for an acute stroke in two tertiary hospitals. We addressed the question whether endogenous estradiol is associated with stroke severity on admission and functional outcome 1 month after stroke, as assessed by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), respectively. Results: Estradiol levels were significantly related to stroke severity on admission, as expressed by NIHSS, even after correcting for confounding factors in the multivariate analysis (beta 0.353, P < 0.001). Estradiol was an independent determinant of 1-month mortality and adverse functional outcome (mRS = 4), [odds ratio (OR) with 95% confidence intervals (CI): 3.341 (1.6176.902), P = 0.001 and 2.277 (1.2734.074), P = 0.006, respectively]. Conclusions: We identified an independent association of endogenous estradiol levels with stroke severity and short-term mortality and outcome. These findings suggest challenging the role of estradiol as a neuroprotective agent

Long-term outcome in posterior cerebral artery stroke

Introduction: Previous studies on posterior cerebral artery (PCA) strokes focused mainly on topography and underlying pathophysiology. However, there are no data on long-term prognosis and its association with the localization of the infarct. Methods: All consecutive PCA strokes registered in the Athens Stroke Outcome Project between 01/1998 and 12/2009 were included in the analysis. The New England Posterior Circulation Registry criteria were applied to classify them in relation to topography: (i) pure PCA infarcts, including pure cortical-only and combined cortical/deep PCA infarcts (groups A and B respectively), and (ii) PCA-plus strokes, including cortical-only and combined cortical/deep PCA strokes with ≥1 concomitant infarcts outside PCA territory (groups C and D respectively). Patients were prospectively followed up to 10years after stroke. Results: Amongst 185 (8.1%) PCA patients that were followed up for 49.6±26.7months, 98 (53%), 24 (13%), 36 (19.5%), and 27 (14.6%) were classified in group A, B, C, and D, respectively. Infections and brain edema with mass effect were more frequently encountered in PCA-plus strokes compared to pure PCA (P<0.05 and <0.01 respectively). At 6months, 56% of cortical-only PCA patients had no or minor disability, compared to 37%, 36%, and 26% in the other groups (P=0.015). The 10-year probability of death was 55.1% (95%CI: 42.2-68.0) for pure PCA compared to 72.5% (95%CI: 58.8-86.2) for PCA-plus (log-rank 14.2, P=0.001). Long-term mortality was associated with initial neurologic severity and underlying stroke mechanism. Conclusions: Patients with pure PCA stroke have significantly lower risk of disability and long-term mortality compared to PCA strokes with coincident infarction outside the PCA territory. Click to view the accompanying paper in this issue. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS

Increased detection of suspected atrial fibrillation in elderly and female hypertensive patients through home blood pressure monitoring: The HOME-AF study

Background:Episodes of suspected atrial fibrillation are particularly frequent in essential hypertension. This study aimed to investigate the incidence of new suspected atrial fibrillation cases detected through home blood pressure (BP) screening among hypertensive patients. Association of new suspected atrial fibrillation cases with arterial hypertension (AH) phenotypes and the CHA2DS2-VASc score was also investigated.Methods:The prospective study recruited hypertensive patients at least 50 years old from private and hospital hypertensive clinics. An ECG was performed during the first visit. Microlife BP A6 PC was used to measure office and home BP for at least 3 and preferably 7 consecutive days.Results:A total of 2408 AH patients were recruited. Suspected atrial fibrillation was detected by BP monitor in 12.5% of patients. CHA2DS2-VASc was greater in hypertensive patients with suspected atrial fibrillation detection, as compared with all other hypertensive patients (3.3 ± 1.4 vs. 2.8 ± 1.4, P < 0.0001). Suspected atrial fibrillation detection was associated with advanced age (≥ 75 years, P < 0.0001) and female sex (P = 0.01). A nonsignificant association between suspected atrial fibrillation detection and history of chronic heart failure/left ventricular dysfunction was observed (P = 0.06). In the multivariate analysis, age and sex were the only independent risk factors with patients at least 75 years old having more than twice the risk of suspected atrial fibrillation compared with patients less than 64 years old. No differences between new suspected atrial fibrillation cases and AH phenotype (white coat/uncontrolled/masked hypertension) were identified.Conclusion:In our cohort of hypertensive patients, suspected atrial fibrillation was common particularly among elderly and female patients. These results underline the need for early suspected atrial fibrillation detection to minimize the increased thromboembolic risk associated with hypertension. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

The type of atrial fibrillation is associated with long-term outcome in patients with acute ischemic stroke

Background/objectives: We aimed to investigate the association between the type of atrial fibrillation (AF) and long-term outcome in terms of mortality and stroke recurrence in patients with ischemic stroke and non-valvular AF. Methods: All consecutive patients admitted with acute ischemic stroke to Alexandra Hospital between 1993 and 2010 were included in the analysis. Patients were categorized in 3 groups according to the type of AF (paroxysmal, persistent, and permanent) and were followed up for up to 10 years after the index stroke or until death. The endpoints were inhospital, 30-day and 10-year stroke recurrence, and 30-day and 10-year all-cause mortality. The Kaplan-Meier product limit method was used to estimate the probability of 10-year stroke recurrence and survival. Multivariate Cox proportional hazard models were used to identify significant predictors of stroke recurrence and all-cause mortality. Results: There were 811 patients (419 females, 392 males) with non-valvular AF and mean age of 75.8 +/- 9.4 years. 277 (34.2%) patients had paroxysmal AF, 165 (20.3%) persistent and 369 (45.5%) permanent. Inhospital stroke recurrence rate was low (1.8%) and similar among the 3 patient groups; on the contrary, the probability of 10-year stroke recurrence was significantly higher in patients with permanent AF (p<0.01 by log-rank test). The probability of 10-year survival was significantly higher in patients with paroxysmal AF (p<0.001 by log-rank test). The type of AF was a significant predictor of 10-year stroke recurrence and mortality. Patients with permanent AF had higher risk of stroke recurrence (HR: 1.78, 95%CI: 1.21-2.61) and mortality (HR: 1.55, 95%CI: 1.20-1.99) compared to patients with paroxysmal AF. Conclusions: Long-term outcome in stroke patients with AF is associated with the type of AF; patients with paroxysmal AF have lower rates of stroke recurrence and mortality. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Prevalence of atrial fibrillation in Greece: The Arcadia Rural Study on Atrial Fibrillation

Introduction Atrial fibrillation (AF) is a major factor for stroke and stroke-associated mortality, and its incidence is increasing during the last decades. There are only scarce data about its prevalence in Greece. We designed an epidemiological cross-sectional study to estimate the prevalence of AF in Greece and evaluate the adequacy of anticoagulant treatment in AF patients. Subjects and methods The Arcadia Rural Study on Atrial Fibrillation (ARSAF) was conducted between 2002-2003 in five rural villages of the Arcadia province (Greece) with a permanent population of 1312 individuals. Patients had a thorough medical examination and electrocardiogram, and information was collected about their medical history and comorbidities. CHADS 2 score was used to determine stroke risk for participants with AF. Results 1155 subjects (88% of the entire population) participated in the study. The overall prevalence of AF was 3.9% showing an increasing trend with increasing age ranging from 0.4% in patients &amp;lt; 55 years to 10.7% in patients &amp;gt; 84 years. Among patients with AF, 14 (32%) had paroxysmal AF. The presence of AF was associated with increasing age (OR: 1.67 for every 10 years increase, 95% CI: 1.26-2.15), hypertension (OR: 2.12, 95% CI: 1.02-4.14), heart failure (OR: 11.85, 95% CI: 4.92-28.56) and prior cerebrovascular disease (OR: 4.17, 95% CI: 1.44-12.06). Among these subjects with AF, 12 (26.6%) were considered as low-risk (CHADS 2 = 0), 18 (40.0%) as intermediate-risk (CHADS 2 = 1), and 15 (33.3%) as high-risk (CHADS 2 &amp;gt; 1) patients for stroke. 25 (55.5%) patients with AF did not receive appropriate antithrombotic treatment. Conclusion The prevalence of AF in Greece is similar to other countries and increases with increasing age

Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer

LINE-1 and Alu elements are non-LTR retrotransposons, constituting together over 30% of the human genome and they are frequently hypomethylated in human tumors. A relationship between global hypomethylation and genomic instability has been shown, however, there is little evidence to suggest active role for hypome-thylation-mediated reactivation of retroelements in human cancer. In our study, we examined by Pyrosequencing the methylation levels of LINE-1 and Alu sequences in 48 primary nonsmall cell carcinomas and their paired adjacent tissues. We demonstrate a significant reduction of the methylation levels of both elements (p = 7.7 × 10-14 and 9.6 × 10-7, respectively). The methylation indices of the 2 elements correlated (p = 0.006), suggesting a possible common mechanism for their methylation maintenance. Genomic instability was measured utilizing 11 fluorescent microsatellite markers located on lung cancer hot-spot regions such as 3p, 5q 9p, 13q and 17p. Hypomethylation of both transposable elements was ass o5ciated with increased genomic instability (LINE, p = 7.1 × 10-5; Alu, p = 0.008). The reduction of the methylation index of LINE-1 and Alu following treatment of 3 lung cell lines with 5-aza-2&apos;-deoxycitidine, consistently resulted in increased expression of both elements. Our study demonstrates the strong link between hypomethylation of transposable elements with genomic instability in non-small cell lung cancer and provides early evidence for a potential active role of these elements in lung neoplasia. As demethylating agents are now entering lung cancer trials, it is imperative to gain a greater insight into the potential reactivation of silent retrotransposons in order to advance for the clinical utilization of epigenetics in cancer therapy. © 2008 Wiley-Liss, Inc

Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF-κB pathway

Unstable atherosclerotic plaques of the carotid arteries are at great risk for the development of ischemic cerebrovascular events. The degradation of the extracellular matrix by matrix metalloproteinases (MMPs) and nitric oxide induced apoptosis of vascular smooth muscle cells (VSMCs) contribute to the vulnerability of the atherosclerotic plaques. Basic fibroblast growth factor (bFGF) through its mitogenic and angiogenic properties has already been implicated in the pathogenesis of atherosclerosis. However, its role in plaque stability remains elusive. To address this issue, a panel of human carotid atherosclerotic plaques was analysed for bFGF, FGF-receptors-1 and -2 (FGFR-1/-2), inducible nitric oxide synthase (iNOS) and MMP-9 expression. Our data revealed increased expression of bFGF and FGFR-1 in VSMCs of unstable plaques, implying the existence of an autocrine loop, which significantly correlated with high iNOS and MMP-9 levels. These results were recapitulated in vitro by treatment of VSMCs with bFGF. bFGF administration led to up-regulation of both iNOS and MMP-9 that was specifically mediated by nuclear factor-κB (NF-κB) activation. Collectively, our data demonstrate a novel NF-κB-mediated pathway linking bFGF with iNOS and MMP-9 expression that is associated with carotid plaque vulnerability. © 2010 The Authors. Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P &lt; 0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P &lt; 0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P &lt; 0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity. © 2006 Elsevier Inc. All rights reserved

CHADS(2), CHA(2)DS(2)-VASc, and long-term stroke outcome in patients without atrial fibrillation

Objective: CHADS(2) and CHA(2)DS(2)-VASc scores are used to assess stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with stroke outcome in non-AF stroke patients. Methods: Consecutive patients with acute first-ever ischemic stroke but without AF were classified into subgroups according to prestroke CHADS(2) and CHA(2)DS(2)-VASc scores and followed up for 5 years. The end points were death, stroke recurrence, and a composite of major cardiovascular events. Results: Among 1,756 patients (aged 67.2 +/- 12.3 years, 68.2% males), there were 258 (14.7%), 617 (35.3%), and 878 (50.0%) patients with low, intermediate, and high CHADS(2) score, respectively. The corresponding figures for CHA(2)DS(2)-VASc subgroups were 110 (6.3%), 255 (14.5%), and 1,391 (79.2%). There were significant differences between CHADS(2) subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 12.3, p = 0.002), and cardiovascular events (log-rank test = 19.4, p < 0.001). Similarly, there were significant differences between CHA(2)DS(2)-VASc subgroups in 5-year mortality (log-rank test 5 74.5, p < 0.0001), stroke recurrence (log-rank test = 10.6, p = 0.005), and cardiovascular events (log-rank test = 16.4, p < 0.001). Compared with the low-risk group, patients in intermediate-and high-risk CHADS(2) subgroups had higher 5-year mortality (hazard ratio [HR]: 2.22 [95% confidence interval {CI}: 1.78-2.77] and 3.66 [95% CI: 2.38-5.62], respectively), stroke recurrence (HR: 1.74 [95% CI: 1.09-2.79] and 1.71 [95% CI: 1.08-2.71], respectively), and cardiovascular events (HR: 1.78 [95% CI: 1.23-2.57] and 1.86 [95% CI: 1.30-2.67], respectively). Compared with the low-risk group, patients in the high-risk CHA(2)DS(2)-VASc subgroup also had higher 5-year mortality (HR: 3.56, 95% CI: 1.89-6.70), stroke recurrence (HR: 2.93, 95% CI: 1.30-6.61), and cardiovascular events (HR: 2.71, 95% CI: 1.49-4.95). Conclusions: Prestroke CHADS(2) and CHA(2)DS(2)-VASc scores predict long-term stroke outcomes in non-AF patients with acute ischemic stroke. These scores may provide a simple way of stroke prognostic risk stratification among non-AF stroke patients. Neurology (R) 2013; 80: 1009-101

The impact of moderate to severe osteoarthritis on the physical performance and quality of life: a cross-sectional study in Greek patients (PONOS study)

Abstract Background Osteoarthritis (OA) represents a leading cause of disability with limited data available for the Greek patients. Objectives To evaluate the impact of moderate to severe symptomatic hip/knee OA under treatment on physical performance and quality of life. Methods A non-interventional, cross-sectional, epidemiological study of patients with moderate/severe OA, recruited in a single visit from 9 expert sites in Athens, Greece. Assessments were based on commonly used outcome scales: the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol-5-Dimensions 3-levels questionnaire (EQ-5D-3L). Results One hundred sixty-four patients were included in the analysis. Most of the patients were females (78.7%), with a mean age of 70.5 ± 10.2 years. Comorbidities were reported by 87.2% of patients with hypertension being the most frequently reported (53.7%), followed by dyslipidemia (31.1%), obesity (24.4%) and diabetes mellitus (23.2%). Paracetamol was the most common treatment (96%), followed by NSAIDs (75%), opioids (50%) and locally applied medications (42.7%). Both hip and knee OA patients showed substantial deterioration in health-related quality of life (QoL) and health status as reflected by the HOOS/KOOS (Function in sport and recreation was the most impaired subscale, followed by Hip- or Knee-related QoL). The mean EQ-5D-3L index score was 0.396 ± 0.319 and the mean EQ-VAS score was 52.1 ± 1.9. When compared indirectly to the local population norms our OA population had worse QoL indices. Conclusion Our findings suggest the functional disability and impaired QoL of Greek patients with moderate/severe hip/knee OA under treatment emphasizing the need for novel treatments that will reduce the burden of the disease