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Little is known about whether venous thromboembolism (VTE) causes worse critical limb events in populations with atrial fibrillation (AF). A retrospective cohort study using claims data from Taiwan's National Health Insurance program between 2001 and 2013 compared AF patients with or without VTE. Outcomes were percutaneous transluminal angioplasty (PTA), amputation, systemic thromboembolism, all-cause mortality, cardiovascular death, ischemic stroke, and acute myocardial infarction. Patients ( n = 316,817) with newly diagnosed AF were analyzed; of those, 2514 (0.79%) had VTE history. After inverse probability of treatment weighting, a history of VTE was significantly associated with higher risks of PTA (3.3 vs 2.2%; subdistribution hazard ratio [SHR] 1.47; 95% confidence interval [CI] 1.17-1.84); above knee amputation (0.7 vs 0.3%; HR 2.15; 95% CI 1.10-4.21); systemic thromboembolism (5.8 vs 3.9%; SHR 1.48; 95% CI 1.21-1.80); all-cause mortality (53 vs 46.4%; HR 1.20, 95% CI 1.12-1.29); and cardiovascular death (34.8 vs 29.4%; HR 1.25, 95% CI 1.14-1.36). In conclusion, VTE might increase the risk of critical lower limb events (PTA and above-knee amputation), systemic thromboembolism, and mortality in the AF population. However, current data cannot confirm a causal relationship between VTE and clinical outcomes in this population.

Background: Enhancing detection of unrecognized atrial fibrillation among acute ischemic stroke patients is crucial for secondary stroke prevention., Aim: To evaluate whether the detection rate of new atrial fibrillation in acute ischemic stroke patients without known atrial fibrillation could be improved by doing serial 12-lead electrocardiograms once daily for five days, compared with conventional 24-h Holter monitoring (24-h Holter)., Methods: We conducted a randomized clinical trial to compare the detection rates of paroxysmal atrial fibrillation between serial electrocardiograms versus 24-h Holter from October 2015 to October 2018 at six hospitals. Eligible participants were acute ischemic stroke patients with aged ≥65 years, with neither atrial fibrillation history nor any presence of atrial fibrillation on baseline electrocardiogram at admission. The primary outcome was newly detected electrocardiogram in the serial electrocardiograms and 24-h Holter group., Results: Among 826 patients, baseline characteristics were similar between both groups. In the intention-to-treat analysis, there was no statistical difference between serial electrocardiograms versus 24-Holter to detect atrial fibrillation (8.4% vs. 6.9%; adjusted odds ratio 1.17, 95% confidence interval 0.69-2.01). Stepwise multivariate logistic regression revealed age ≥80 years and history of heart failure were associated with detection of paroxysmal atrial fibrillation whereas patients with lacunar infarction had lower odds for detection of paroxysmal atrial fibrillation., Conclusions: Serial electrocardiograms had comparable detection rate of paroxysmal atrial fibrillation compared with 24-h Holter and might be a viable alternative to 24-h Holter as a first-line approach to survey for potential paroxysmal atrial fibrillation among elderly patients with acute ischemic stroke. Clinical Trial Registration: URL https://clinicaltrials.gov/ct2/show/NCT02578979Unique Identifiers: NCT02578979.

Atrial fibrillation (AF) is a major independent risk factor of stroke and anticoagulation therapy is needed in patients with AF after ischemic stroke. However, the detection rate of AF is low after ischemic stroke. Developing a prediction model for newly diagnosed AF after ischemic stroke will help to assess the subclinical AF.We identified 98,103 patients with diabetes mellitus (DM) and 261,893 patients without DM, who were not AF history and admitted for newly ischemic stroke from the National Health Insurance Research Database in Taiwan. The prediction model for 3-year incidence of AF after ischemic stroke was derived from multivariate logistic regression and also the accuracy rate of the prediction model was compared with CHA2DS2-VASC and CHADS2 scores as a reference.Four thousand nine hundred seventy six patients in the DM cohort and 16,127 patients in the non-DM cohort developed AF during 3 years of follow-up. The variables in the point-based prediction model for non-DM patients (range: -3-28), included age, heart failure, coronary artery disease, gout, obstructive pulmonary disease, hypertension, female, and statin use, while those for DM patients (range: -2-30) included age, heart failure, coronary artery disease, chronic kidney disease, hypertension, obstructive pulmonary disease, and statin use. Compared to the CHADS2 and CHA2DS2-VASc scoring systems, this scoring system was better at predicting 3-year risk of AF after ischemic stroke in both cohorts.This model might be useful in evaluating the benefit of insertable cardiac monitor implantation and anticoagulation agents in individual patients after ischemic stroke.

Background and Aims: Statins improve clinical outcomes in patients with ischemic stroke but there is no evidence of the effect of continuing long-term statin therapy in patients with intracerebral hemorrhage (ICH). The aim of this study was to evaluate the impact of continuing statin after ICH., Methods: Data on patients with ICH was retrieved from the National Health Insurance Research Database of Taiwan. The final population was separated into two groups according to those who continued and those who discontinued statin treatment. All-cause mortality and cardiovascular outcomes were analyzed after a 3 year follow-up after propensity score matching (PSM)., Results: Of the 114,101 patients with ICH, who were initially enrolled, 2468 patients with dyslipidemia and ICH were included. After PSM, the benefit of statin therapy on mortality appeared from 1 year to the end of the 3-year follow-up period after discharge (statin group versus non-statin group: 4.9% vs.12.3% at 1 year (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.26-0.57) and 12.9% vs. 25.3% at the end of the 3 year follow-up period (HR, 0.45; 95% CI, 0.35-0.58). Compared with the patients using lipophilic statins, those using hydrophilic statins had a significantly lower incidence of all-cause mortality (HR = 0.65, 95% CI = 0.43-0.99). There were no differences between those prescribed moderate-intensity statins and those prescribed high-intensity statins in terms of stroke and all-cause mortality (HR = 0.76; 95% CI = 0.40-1.46)., Conclusions: There was a lower risk of all-cause mortality following ICH in patients who continued statin treatment compared with those without statin treatment, especially in those treated with hydrophilic statins., (Copyright © 2018. Published by Elsevier B.V.)

Background: The tendency for haemorrhagic stroke in patients with chronic HCV infection has emerged recently but the finding may be confounded by comorbidities. Proving the causality between HCV infection and haemorrhagic stroke is mandatory. Our study was designed to investigate the incidence of intracranial haemorrhage in HCV-infected patients with and without treatment., Methods: In the 11-year and population-based retrospective study, we acquired data from the Taiwan National Health Insurance Research Database. The patients with major comorbidities were excluded and 97,198 HCV-infected patients were included for analysis. Treated and untreated cohorts were matched with propensity score to make the confounding factors in two groups comparable. Cox proportional hazard regression analysis was performed to evaluate the hazard ratio of haemorrhagic stroke in the cohorts. We applied survival analysis to compare the cumulative incidence of outcome events between the two cohorts., Results: After matching, the incidence density (ID) of haemorrhagic stroke in the untreated cohort is significantly higher than in the treated cohort (ID: 1.0 versus 0.6 events per 1,000 person-years; P=0.0014). The adjusted hazard ratio (aHR) of haemorrhagic stroke is significantly reduced in the treated group (P<0.05). Cumulative incidence of haemorrhagic stroke is significantly lower in the treated group than in the untreated group (P=0.013)., Conclusions: The study demonstrates that antiviral therapy significantly reduces the events of intracranial haemorrhage in HCV-infected patients and consolidates the novel concept that chronic HCV infection is a risk factor for haemorrhagic stroke.

Context: Statin is the main lipid-lowering therapy for type 2 diabetes mellitus patients. Recent evidence suggested the cardiovascular protective effects of ezetimibe-simvastatin in acute coronary syndrome patients., Objective: To investigate the effect of ezetimibe-simvastatin combination therapy on stroke prevention among diabetic stroke patients. Design, Setting, Participants, and Outcome Measures: This is a retrospective cohort study. Between March 1, 2009 and December 31, 2011, all patients with type 2 diabetes mellitus in Taiwan's National Health Insurance Research Database were screened. Those admitted for ischemic stroke (IS) were recruited and divided into 10-mg ezetimibe-20-mg simvastatin (EZ-SIM), 40-mg atorvastatin (ATOR), and 20-mg simvastatin (SIM) groups for further analyses. The primary outcomes were IS, myocardial infarction, and death from any cause. Patients were followed from index hospitalization to the date of death, loss of follow-up, or study termination., Results: During the 34-month follow-up period, the risk of recurrent IS in the SIM group was higher than that of the ATOR (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.46-2.82) and EZ-SIM (HR, 1.69; 95% CI, 1.14-2.50) groups. The risk of recurrent IS was not significantly lower in the EZ-SIM compared with the ATOR group (HR, 1.20; 95% CI, 0.85-1.69). The incidence of composite endpoint was highest in the SIM group (28.2%), followed by the ATOR (16.1%) and EZ-SIM (15.4%) groups. The multivariate adjusted survival curve showed lower trends of recurrent IS in the EZ-SIM and ATOR groups compared with the SIM group., Conclusions: High-potency lipid-lowering therapy effectively reduces the risk of recurrent IS in diabetic patients regardless of ATOR or EZ-SIM combination therapy.

Background: Tamoxifen is used for breast cancer treatment and has been reported to be beneficial for the cardiovascular system, but it is unclear whether tamoxifen exhibits a favorable cardiovascular effect in Asian patients., Methods and Results: From January, 1998 to December, 2006, a breast cancer cohort study was conducted using the Taiwan National Health Insurance database. Patients were divided according to whether tamoxifen was used. Study endpoints were occurrence of acute myocardial infarction (AMI), ischemic or hemorrhagic stroke and total cardiovascular events. A total of 3,690 female subjects were enrolled (mean age 50.1±11.3), 2,056 of whom received tamoxifen and 1,634 did not. During a mean follow-up of 6.9 years, the tamoxifen group had a significantly lower incidence of AMI (0.15% vs. 0.67%, P=0.008), ischemic stroke (1.99% vs. 3.30%, P=0.008), hemorrhagic stroke (0.15% vs. 0.55%, P=0.029), and total cardiovascular events (2.24% vs. 4.16%, P<0.001) than the non-exposed group. After adjusting for comorbidities, tamoxifen was independently associated with a reduced risk of myocardial infarction (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.07-0.70, ischemic stroke (HR 0.52; 95% CI 0.35-0.78), hemorrhagic stroke (HR 0.25; 95% CI 0.07-0.92), and total cardiovascular events (HR 0.54; 95% CI 0.37-0.78)., Conclusions: In Asian female breast cancer patients, tamoxifen use was associated with reduced risks of AMI, ischemic, hemorrhagic stroke and total cardiovascular events.

Objective: To investigate whether SSc increases the risk of ischaemic stroke in a large, nationwide cohort study., Methods: From the Registry of Catastrophic Illness in Taiwan, we obtained data for 1280 patients with a diagnosis of SSc from 1997 to 2006. We also obtained data for 10 age-, gender-, comorbidity- and enrolment date-matched controls per SSc patient from the Longitudinal Health Insurance 2000. All study subjects were followed up from the date of enrolment until they developed ischaemic stroke, death or to the end of 2006, whichever was earlier. We used Cox's regression model with adjustment for age, gender and comorbid disorders to assess the independent factors in determining the risk of developing ischaemic stroke., Results: We identified 1238 SSc patients and 12 380 controls. Among these patients, 765 (86 SSc patients and 679 controls) had developed ischaemic stroke during the median 4.7 years (0.1-10.0 years) of follow-up. Patients with SSc had a significantly higher incidence of ischaemic stroke when compared with controls (16.5/1000 vs 11.5/1000 person-year). After multivariate analysis, SSc was associated with a 43% increase in ischaemic stroke risk (95% CI 12%, 83%; P = 0.004). Additionally, the medication usually being prescribed among SSc patients did not alter the risk of further ischaemic stroke., Conclusion: We conclude that SSc is independently associated with higher risk of ischaemic stroke development.

Background: Systemic lupus erythematosus (SLE) has been reported to be associated with an increased risk of cardiovascular disease. However, most studies have been criticized for either a small sample size or the lack of a prospective control. Our study investigated the relationship of SLE and the subsequent development of ischemic stroke using a nationwide, population-based database in an Asian population., Methods: From 2000 to 2007, we identified a study cohort consisting of a total of 11,637 newly diagnosed SLE patients using the National Health Insurance Research Database in Taiwan. A control cohort of 58,185 subjects without SLE, matched for age, gender, and comorbidities were selected for comparison to observe the occurrence of ischemic stroke in these two groups., Results: During a follow-up period of up to 7 years, ischemic stroke developed in 258 (2.22%) of the patients with SLE and in 873 (1.5%) of patients in the comparison cohort. Kaplan-Meier analysis also revealed a tendency of SLE patients toward ischemic stroke development (log rank test, p = 0.001). After Cox model adjustment for patients' demographic characteristics and selected comorbidities, patients with SLE were found to have a 1.67-fold (95% CI, 1.45 to 1.91) higher risk of developing ischemic stroke., Conclusion: Patients with SLE have an increased risk of stroke.

Background: Carotid intima-medial thickness (IMT) is a surrogate marker of subclinical atherosclerosis. This study aimed to investigate the impacts of genetic variants on IMT and future development of ischemic stroke in a cohort, followed by an independent replication study., Methods: B-mode carotid ultrasound was performed among 3330 healthy adults in the CVDFACT cohort study, and the genetic effects of atherosclerosis-related genes including connexin37 (GJA4), C-reactive protein (CRP), paraoxonase (PON1), adiponectin (ACDC), angiotensin-converting enzyme (ACE), beta-adrenergic receptor (ADRB1, ADRB2), antithrombin III (SERPINC1), and kinesin family member 6 (KIF6) were evaluated by a multivariate regression model, adjusting for traditional vascular risk factors. Study subjects were prospectively followed for the development of ischemic stroke to assess the prognostic impacts of these genetic variants. An independent case-control study was performed to replicate the genetic association from the cohort study., Results: The T allele of connexin37 C1019T polymorphism significantly affected IMT (β=0.014, p=0.013) after adjusting for traditional risk factors. During an average follow-up period of 10.7 years, 80 patients with ischemic stroke (2.4%) were identified. The connexin37 1019T allele was significantly associated with an increased rate of ischemic stroke under an additive model, with hazard ratios (HR) of 2.83 (95% confidence interval, 1.2-6.66) and 1.69 (95% confidence interval, 1.06-2.71), comparing TT and CT genotype with CC, respectively. After Cox analysis, age (HR, 1.78 every 10 years), diabetes mellitus (HR, 2.63), hypertension (HR, 2.08), and the T allele of C1019T polymorphism of GJA4 (HR, 1.69) were identified as independent predictors of ischemic stroke. The relationship between T allele of C1019T polymorphism of GJA4 gene and ischemic stroke was also confirmed by an independent association study., Conclusion: Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We report the case of a 65-year-old man with a 6-year history of hypertension who presented with dilated cardiomyopathy, a transient cerebrovascular event, paroxysmal sweating, and intractable hypertension. Coronary angiography revealed no abnormality, but diagnostic testing was pursued because of the severe sweating and hypertension. Two-dimensional echocardiography showed 4-chamber dilatation with decreased left ventricular contractility. Further investigation, including a computed tomographic scan of the abdomen, led to a diagnosis of pheochromocytoma. Surgical resection of a left adrenal pheochromocytoma quickly resolved the patient's hypertension and resulted in substantially improved cardiac function after 4 months. Although pheochromocytoma has rarely been reported in the presence of both dilated cardiomyopathy and cerebrovascular events, it should be included in the differential diagnosis when patients present with dilated cardiomyopathy and a cerebrovascular event that have no obvious cause.