Higher Risk Of Ischemic Stroke Research Articles

Abstract WMP38: One Year Medicare Spending On Beneficiaries In Atrial Fibrillation Not Being Treating With Long-term Anticoagulants Experiencing A Hospitalization For Ischemic Stroke

Background: It is well known that individuals in atrial fibrillation (AF) who are not using anticoagulants are at higher risk of Ischemic Stroke (IS). These hospitalizations result in the utilization of significant healthcare resources in addition to reducing patients’ quality of life. The purpose of this study is to estimate how much the Medicare program spends treating a Medicare beneficiary (MB) with AF who are not being anticoagulated with an IS hospitalization and the 12-months following discharge. Method: The study population consisted of all MBs in the fee-for-service program who had a hospitalization for IS and were discharged between January 1, 2018 to December 31, 2018. A total of 50,509 MBs met the study inclusion criteria and were not excluded due to prior history of stroke or on long-term anticoagulants. The study period for accumulating Medicare spending at healthcare facilities is for the index hospitalization and all facility claims that occurred within 12-months of the index hospital discharge date. Results: Average total Medicare spending per MB for the study population was $46,867±$49,212 resulting in total Medicare spending of nearly $2.5 billion during the study period. Highest average spending per MB was for hospital services $25,848 (of which $15,790± $20,984 occurred during the index hospitalization and $10,058±$21,956 during readmission during the follow-up period. The Medicare program also spent over $3,000 per study patient at skilled nursing facilities ($8,131±$14,979), rehabilitation facilities ($5,538±$12,739), and outpatient facilities or emergency departments ($3,056±$7,495). At least, 19% of MB died during the study period. Medicare spent $25,397±$30,259 on those MBs that died during their index hospitalization and $67,276±$65,021 on those MBs that survived their index IS hospitalization but died during the follow-up period. Conclusion: MBs with AF who are not being treated with anticoagulants and suffer an ischemic stroke result in one-year Medicare Part A program spending of approximately $47,000 per person compared to the average Medicare spending for all services of approximately $12,000 per beneficiary in 2018. Identification of MB in AF and treatment with anticoagulants would save CMS significant dollars.

Serum Fatty Acids Are Associated with a Higher Risk of Ischemic Stroke.

Stroke prevention, a significant public-health concern, begins with recognizing and addressing risk factors. Interventions targeted at modifiable risk factors can effectively prevent ischemic stroke, while Omega-3 fatty acids have been shown to improve stroke outcomes. Our study aimed to investigate the relationship between ischemic-stroke risk factors and fatty acids using a prospective observational study with 274 patients. We collected clinical data on risk factors and measured fatty-acid levels using high-performance liquid chromatography coupled with mass spectrometry. We found that several risk factors, including age, sex, smoking, atrial fibrillation, dyslipidemia, and previous stroke history, had a direct relationship with fatty acids. Of these, smoking had the most significant impact, negatively impacting levels of docosahexaenoic and eicosapentaenoic acid. Conversely, dyslipidemia and atrial fibrillation positively correlated with fatty acids, particularly in female patients and those with recurrent strokes. Age was found to directly correlate with other risk factors and variations in fatty-acid ratios. The stroke rate was higher in males than females before the age of 70, but this trend reversed. Our findings suggest that better management of risk factors, particularly modifiable lifestyle factors, could improve fatty-acid profiles and the balance of Omega-3 and Omega-6 in patients with ischemic stroke.

Family history, waist circumference and risk of ischemic stroke: A prospective cohort study among Chinese adults

Background and aimsThe associations between genetic factors and waist circumference (WC) with stroke risk have been evaluated in Western studies. However, evidence of this association has rarely been reported in the Chinese population. This study aimed to evaluate the association between WC and family history of stroke (FHS) with ischemic stroke (IS) risk among Chinese adults and to further explore the potential interaction of these associations. Methods and resultsThe China Kadoorie Biobank (CKB) study recruited 35,508 participants aged 30–79 years from the Qingdao urban area during 2004–2008. A total of 33,355 participants were included in study. Cox regression analysis was used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the independent and interactional associations between FHS and WC and IS risk. Participants with FHS had a 29% (HR = 1.29, 95% CI: 1.12–1.50) higher IS risk than those without FHS. Participants with excessive WC (85 cm for males and 80 cm for females) had a 78% (HR = 1.78, 95% CI: 1.51–2.10) higher IS risk than those with normal WC. The combined effect of FHS and excessive WC on IS was statistically significant (HR = 2.29, 95% CI: 1.84–2.86). The present study further found statistically significant multiplicative interactions of FHS and WC with IS risk (Pinteraction < 0.001). ConclusionThe present study indicated that FHS and WC were significantly associated with an increased risk of IS. The association between FHS and IS was associated with excessive WC.

Particulate Air Pollution Exposure and Stroke among Adults in Israel.

Stroke is the second most common cause of death and disability in the world. Many studies have found fine particulate matter (PM2.5) exposure to be associated with an increased risk of atherosclerotic cardiovascular disease, mostly focusing on ischemic heart disease and acute myocardial infarction. In a national analysis conducted in Israel-an area with unique climate conditions and high air pollution levels, we estimated the association between short-term PM2.5 exposure and ischemic stroke, intracerebral hemorrhage (ICH), or transient ischemic attacks (TIA). Using the Israeli National Stroke Registry, we obtained information on all stroke cases across Israel in 2014-2018. We obtained daily PM2.5 exposures from spatiotemporally resolved exposure models. We restricted the analytical data to days in which PM2.5 levels did not exceed the Israeli 24 h standard (37.5 µg/m3). We repeated the analysis with a stratification by sociodemographic characteristics and comorbidities. For all outcomes, the exposure-response curves were nonlinear. PM2.5 exposure was associated with a higher ischemic stroke risk, with larger effect estimates at higher exposure levels. Although nonsignificant, the exposure-response curve for TIA was similar. The associations with ICH were nonsignificant throughout the PM2.5 exposure distribution. The associations with ischemic stroke/TIA were larger among women, non-Jewish individuals, older adults, and individuals with diabetes, hypertension, and ischemic heart disease. In conclusion, short-term PM2.5 exposure is associated with a higher risk for ischemic stroke and possibly TIA, even when PM2.5 concentrations do not exceed the Israeli air quality guideline threshold. Vulnerability to the air pollution effects differed by age, sex, ethnicity, and comorbidities.

Use of CHA2DS2-VASc score to predict the risk of ischemic stroke and mortality in patients who underwent coronary artery bypass grafting surgery: a retrospective cohort study.

Ischemic stroke and postoperative atrial fibrillation (POAF) are frequently seen after coronary artery bypass grafting (CABG). CHA2DS2-VASc scoring system is used to predict ischemic stroke and POAF. This study aimed to evaluate CHA2DS2-VASc scores in predicting ischemic stroke after CABG and analyze the effect of POAF on the relationship between CHA2DS2-VASc scores and ischemic stroke. Demographic and clinical characteristics of patients who underwent CABG were retrospectively recorded. CHA2DS2-VASc score was calculated for each patient and stratified into low- and high-risk groups. The heart rhythm of the patients was monitored during in-hospital follow-up and ischemic stroke was evaluated. Ischemic stroke and POAF were the primary and secondary outcomes. There were 383 patients (mean age of 63.1 ± 10.4 years). Ischemic stroke developed in eight (2.1%) patients. There were 248 (64.8%) high-risk patients with CHA2DS2-VASc scores. Patients with ischemic stroke were significantly older (p = 0.021) and had higher CHA2DS2-VASc scores (p < 0.001). Low and high-risk groups did not reveal any significant difference for ischemic stroke (p = 0.055). There were 56 (14.7%) patients with POAF. The relationship between CHA2DS2-VASc scores and ischemic stroke was not affected by POAF (p = 0.739). CHA2DS2-VASc scores of ≥3 predicted ischemic stroke (p < 0.001) with 100% sensitivity and 64.5% specificity. Ischemic stroke was associated with a higher mortality risk after CABG. Higher CHA2DS2-VASc scores were associated with higher ischemic stroke risk. POAF did not significantly affect the relationship between CHA2DS2-VASc scores and ischemic stroke. CHA2DS2-VASc score can be used to predict ischemic stroke and mortality following CABG.

Women's reproductive traits and ischemic stroke: a two-sample Mendelian randomization study.

We conducted a Mendelian randomization (MR) study to disentangle causal associations between women's reproductive behaviors and ischemic stroke (IS) and investigate the roles of two modifiable risk factors (body mass index (BMI) and educational attainment (EA)) in these associations. Using summary-level data from large-scale genome-wide association studies, we performed univariable MR to examine whether there is genetic evidence that women's reproductive traits are causally associated with IS and its subtypes. Multivariable MR and MR mediation analysis were used to investigate whether BMI and EA are common mechanisms or mediators for these associations. A set of sensitivity analyses were conducted to test valid MR assumptions. We observed consistent and statistically significant associations across female and sex-combined analyses for earlier age at first birth (AFB) and age at first sexual intercourse (AFS) with a higher risk of IS and large-artery atherosclerotic stroke (LAS) risk in the primary analysis. The odds ratios of IS per 1 SD increase in genetically predicted early AFB and AFS were 0.93 (95% CI, 0.86-0.99; p=0.046) and 0.83 (95% CI, 0.70-0.97, p=0.020), respectively. Further analyses indicated that BMI played a shared role in AFS and IS/LAS while EA played a shared role in AFS/AFB and IS/LAS as well as a mediator in the path from AFS to IS/LAS. These findings may inform prevention strategies and interventions directed toward relative women's reproductive behaviors and IS. Future studies are warranted to explore other factors related to EA which are responsible for these causalities.

Thrombolysis in central retinal artery occlusion: a retrospective observational study

BackgroundThere is no evidence-based therapy for non-arteritic central retinal artery occlusion (NA-CRAO). Intravenous thrombolysis (IVT) with alteplase in a time window < 4.5 h may lead to a favorable outcome. Purpose of this study was to investigate the feasibility, efficacy and safety of IVT in patients classified as functionally blind.MethodsWe conducted a retrospective observational study of NA-CRAO-patients. All patients underwent an ophthalmological and neurological examination including cerebral magnetic resonance imaging (MRI) for assessment of additional stroke lesions. Patients were treated either conservatively or with IVT within 4.5 h. Visual acuity (VA) was evaluated in logMAR and a categorical analysis was performed.ResultsThirty-seven patients were included in the study, 21 patients in the conservative treatment group (CTG) and 16 patients in the IVT group. The median logMAR visual acuity at admission and discharge was similar in both groups. The medium symptom to treatment time in the IVT group was 158.0 min. 3 patients (19%) of the IVT group showed a favorable outcome, all CTG patients remained at the level of functional blindness. No serious adverse events were observed after IVT. MRI showed additional acute stroke in over one-third of the patients (n = 14).ConclusionsEarly intravenous thrombolysis therapy according to the current stroke protocol n a time window up to 4.5 h after the onset of symptoms was feasible and might be a potential treatment option for NA-CRAO. Patients with NA-CRAO are at very high risk of ischemic stroke and MRI should be done in all patients for optimized treatment and secondary stroke prevention. A prospective randomized study is required.

Homocysteine is associated with higher risks of ischemic stroke: A systematic review and meta-analysis.

BackgroundHigh levels of homocysteine (Hct) have been associated with great risks of ischemic stroke. However, some controversy still exists. We performed a systematic review and meta-analysis to compare the levels of Hct between patients with ischemic stroke and controls.MethodsWe performed a systematic literature search for articles reporting Hct levels of patients with occurrence of ischemic stroke. We employed a random-effects inverse-variance weighted meta-analytical approach in order to pool standardized mean differences, with estimation of τ2 through the DerSimonian-Laird method.ResultsThe initial search yielded 1361 studies. After careful analysis of abstracts and full texts, the meta-analysis included data from 38 studies, which involved almost 16 000 stroke events. However, only 13 studies reported means and standard deviations for cases and controls, and therefore were used in the meta-analysis. Those studies presented data from 5002 patients with stroke and 4945 controls. Standardized mean difference was 1.67 (95% CI 1.00–2.25, P < 0.01), indicating that Hct levels were significantly larger in patients with ischemic stroke compared to controls. Between-study heterogeneity was very large (I2 = 99%), particularly because three studies showed significantly large mean differences.ConclusionThis meta-analysis shows that patients with ischemic stroke have higher levels of Hct compared to controls. Whether this is a modifiable risk factor remains to be assessed through larger prospective cohorts.

Socioeconomic factors and bleeding events in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Low socioeconomic status has been associated with higher risk of ischemic stroke and death in patients with atrial fibrillation (AF). However, whether socioeconomic status affects risk of bleeding events is unknown. We assessed the hypothesis that low income and educational attainment are associated with higher risk of bleeding in patients with AF. The registry-based FinACAF study covers all patients with AF in Finland during 2007-2018. Patients were divided into income quartiles and three categories based on their educational attainment. Outcomes of interest were the first-ever gastrointestinal (GI), intracranial (IC) and any bleeding. We identified 205 019 patients (50.9% female; mean age 72.3 (SD 13.4) years) with incident AF without prior bleeding. Mean follow-up time was 4.0 (SD 3.2) years, during which 25013 (12.2%) patients experienced first-ever any bleeding (incidence rate 3.07 (95% CI 3.03-3.10) /100 patient-years). Low income was independently associated with hazard of any bleeding as well as GI and IC bleeding (adjusted hazard ratios (HRs) comparing lowest vs highest income quartile: 1.13 (1.08-1.17), 1.32 (1.23-1.41) and 1.15 (1.06-1.24), respectively). Income-related bleeding disparities were larger among younger patients under 65years and among men. Education-related bleeding disparities were smaller than income related-disparities (adjusted HRs comparing lowest vs highest educational category: any bleeding 1.06 (1.02-1.11), GI bleeding 1.16 (1.08-1.24), IC bleeding 1.10 (0.93-1.09)). Patients with AF and low income are at higher risk of bleeding, especially GI bleeding.

Augmented risk of ischemic stroke in hypertrophic cardiomyopathy patients without documented atrial fibrillation

Abstract Background Ischemic stroke is a common complication in patients with hypertrophic cardiomyopathy (HCM) (1). Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke in HCM, the risk of ischemic stroke in patients with HCM without documented AF is less recognized (1, 2). This study aimed to determine the risk of ischemic stroke and identify its risk factors in patients with HCM without documented AF. Methods This nationwide population-based cohort study used the Korean National Health Insurance database. After excluding patients with a prior history of AF, thromboembolic events, cancer, or the use of anticoagulants, we identified 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls. The clinical outcome was an incident ischemic stroke. Results During a mean follow-up of approximately 6 years, ischemic stroke occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. Among individuals who developed ischemic stroke, the proportion of AF concomitantly detected accounted for 26.5% (87/328) and 5.8% (26/443) in the HCM and control groups, respectively. The overall incidence of ischemic stroke was 0.716/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.643; 95% CI, 1.424–1.895; P&amp;lt;0.001, Figure 1). The subgroup analysis according to age, sex, and comorbidities (chronic heart failure, hypertension, dyslipidemia, and vascular disease) consistently demonstrated a higher risk of ischemic stroke in the HCM group (P for interaction &amp;gt;0.05). In the HCM group, age ≥65 years (adjusted hazard ratio [HR] 2.741; 95% confidence interval [CI], 2.156–3.486; P&amp;lt;0.001) and chronic heart failure (adjusted HR 1.748; 95% CI, 1.101–2.745; P=0.018) were independent risk factors for ischemic stroke. Overall incidence was 1.360/100 in patients with HCM aged ≥65 and 2.315/100 person-years years in those with chronic heart failure, respectively. Also, compared to controls aged &amp;lt;65 years and without CHF, adjusted HR for ischemic stroke was 4.756 (95% CI 3.807–5.867) in patients with HCM aged ≥65 years and 2.539 (95% CI 1.638–3.936) in those with CHF, respectively (Figure 2). Conclusions Patients with HCM without documented AF are at a higher risk of ischemic stroke than the propensity score-matched general population. Age ≥65 years and chronic heart failure are two strong independent risk factors for ischemic stroke in this population. Funding Acknowledgement Type of funding sources: None.

Microvascular complications, coronary artery disease and the risk of cardiovascular disease in diabetes patients undergoing coronary angiography: a cohort study from the Western Denmark Heart Registry

Abstract Background Diabetes is associated with an increased risk of both microvascular macrovascular complications. The association between microvascular disease and cardiovascular risk, however, is less explored. Aims We aimed to estimate the cardiovascular risk associated with microvascular disease in diabetes patients with and without coronary artery disease. Methods We included every patient who underwent coronary angiography in Western Denmark between 2003–2016. Patients were stratified by microvascular disease (defined as diagnosis retinopathy, nephropathy, or peripheral neuropathy) and coronary artery disease by angiography. Outcomes included major adverse cardiovascular events (myocardial infarction, ischemic stroke, and cardiac death) as a combined outcome and as separate outcomes. Patients were followed for a maximum of 10 years. We estimated 10-year cumulative incidence of each outcome. Incidence rate ratios (IRR) were estimated by a modified Poisson regression model using diabetes patients with neither microvascular disease nor coronary artery disease as reference. Results We included 19,295 patients with diabetes, of whom 1,268 (6.6%) had microvascular disease, 10,161 (52.7%) had coronary artery disease, 3,113 (16.3%) had both microvascular disease and coronary artery disease, and 4,753 (24.6%) had neither microvascular nor coronary artery disease. Median follow-up was 5.9 years (interquartile range 3.3–9.0) Patients with microvascular disease had an increased risk of major adverse cardiovascular events compared to diabetes patients with neither microvascular disease nor coronary artery disease (13.6% versus 10.0%, adjusted IRR 1.45, 95% CI 1.19–1.77, Figure 1). This increased risk was driven by a 3.9% higher risk of ischemic stroke (adjusted IRR 1.53, 95% CI 1.14–2.05, Figure 2), while microvascular disease was not associated with an increased risk of myocardial infarction (adjusted IRR 1.08, 95% CI 0.72–1.62) or cardiac death (adjusted IRR 0.99, 95% CI 0.63–1.56). Patients with both microvascular disease and coronary artery disease had the highest risk of major adverse cardiovascular events (29.3%, adjusted IRR 3.06, 95% CI 2.67–3.50). Conclusion Microvascular disease in diabetes patients without angiographic coronary artery disease is associated with an increased cardiovascular risk. However, this was driven by a higher risk of ischemic stroke than by higher rates of myocardial infarction or cardiac death. In fact, diabetes patients with microvascular disease but no coronary artery disease had the same risk of ischemic stroke as those with combined microvascular disease and coronary artery disease. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Aarhus University Hospital

Impact of metabolic syndrome on the risk of ischemic stroke in non-anticoagulated atrial fibrillation patients having low CHA2DS2-VASc scores

Abstract Background Metabolic syndrome (MetS) predisposes to a thromboembolic state. However, conflicting results have been reported on whether MetS confers an increased risk of ischemic stroke in atrial fibrillation (AF), especially in patients with low CHA2DS2-VASc score who are not indicated for oral anticoagulant therapy. Purpose We investigated the risk of ischemic stroke according to the presence of MetS, the number of MetS components (metabolic burden), and the individual metabolic components in non-anticoagulated AF patients with low CHA2DS2-VASc score. Methods A total of 76,015 oral anticoagulant-naïve AF patients with low CHA2DS2-VASc score (0,1 in male and 1 in female) were included from the Korean National Health Insurance Service database. The status of MetS and individual metabolic components were evaluated based on health examination data within two years of AF diagnosis. We estimated the risk of ischemic stroke according to MetS, metabolic burden, and an individual component of MetS using Cox proportional-hazards models. Results The mean age was 49.8±11.1 years and 52,388 (68.9%) were male. The average CHA2DS2-VASc score was 0.7±0.5 and MetS was prevalent among 21,570 (28.4%) of the study population. During a mean follow-up of 5.1 years, ischemic stroke was developed in 1,395 (1.84%) patients. MetS was associated with a higher risk of ischemic stroke after adjustment for age, sex, lifestyle behaviors, low income, and cardiovascular comorbidities: adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) 1.06–1.33, p=0.002. A positive linear correlation was observed between metabolic burden and ischemic stroke risk. Patients with five MetS components showed the highest aHR of 1.55 (95% CI 1.14–2.11, Figure 1 and Figure 2), whereas those with a single MetS component had a marginal risk of ischemic stroke (aHR 1.18, 95% CI 0.99–1.41). Among individual metabolic components, elevated blood pressure and increased waist circumference was significantly associated with an increased risk of ischemic stroke: aHR (95% CI), 1.45 (1.30–1.62), p&amp;lt;0.001, and 1.15 (1.03–1.30), p=0.016, respectively. Conclusions Among AF patients initially with CHA2DS2-VASc score 0 and 1 with no anticoagulation, the presence of MetS is associated with an increased risk of ischemic stroke. Given the linear incremental correlation between metabolic burden and ischemic stroke, special attention to the care of metabolic derangements is required in AF patients who are not indicated for anticoagulation. Funding Acknowledgement Type of funding sources: None.

Advances in Stroke: Genetics, Genomics, Precision Medicine.

Advances in Stroke: Genetics, Genomics, Precision Medicine.

Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention. The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillationcohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription. We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels. These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.

Efficacy and safety of left atrial appendage closure in patients with atrial fibrillation and high thromboembolic and bleeding risk

Aim. To compare the incidence of thromboembolic and hemorrhagic events after left atrial appendage occlusion (LAAO) or without prevention of thromboembolic events (TEEs) during prospective follow-up of patients with atrial fibrillation (AF) and a high risk of ischemic stroke (IS) who have contraindications to long-term anticoagulant therapy.Material and methods. The study included 134 patients with AF, a high risk of IS, and contraindications to long-term anticoagulation. Patients were divided into 2 groups as follows: the first group included patients who underwent LAAO (n=74), while the second one — those who did not undergo any TEE prevention (n=60). The follow-up period was 3 years. The cumulative rate of all-cause mortality, IS, transient ischemic attacks (TIA), and systemic embolism (SE) was taken as the primary efficacy endpoint. The primary safety endpoint included major bleeding according to GARFIELD registry criteria.Results. The rate of composite efficacy endpoint in the LAAO group was significantly lower than in the group without thromboembolic prophylaxis (5,2 vs 17,4 per 100 patient-years; adjusted odds ratio (OR), 4,08; 95% confidence interval (CI): 1,7-9,5; p=0,001). The rate of major bleeding was comparable in both groups (2,4 in the LAAO group vs 1,3 per 100 patient-years in the group without thromboembolic prophylaxis; adjusted OR, 0,55; 95% CI: 0,1-3,09; p=0,509). In addition, the event rate of net clinical benefit (all-cause mortality + ischemic stroke/TIA/SE + major bleeding) in the LAAO group was also significantly lower (5,9 vs 18,2 per 100 patient-years; adjusted OR, 3,0; 95% CI: 1,47-6,36; p=0,003).Conclusion. Among patients with AF and contraindications to long-term anticoagulation after 3 years of follow-up, LAAO demonstrated the significant reduction of cumulative rate of all-cause mortality and non-fatal thromboembolic events. At the same time, the frequency of major bleeding was comparable between the groups, even taking into account access-site bleeding and postoperative antithrombotic therapy (ATT)-associated bleeding in the LAAO group. Further randomized clinical trials are required to confirm these data.

Genetic Polymorphism of NQO1 Gene is Associated with Susceptibility of Ischemic Stroke in Chinese Han Nationality.

PurposeNAD(P)H: Quinone Oxidoreductase 1 gene (NQO1) polymorphism is associated with the risk of cardiovascular disease. This study was designed to investigate the relationship between NQO1 gene polymorphism and ischemic stroke susceptibility in Chinese Han nationality.Patients and MethodsOne hundred and forty-one patients diagnosed with ischemic stroke and 139 matched control groups were recruited in this study. The polymorphism distribution of rsl800566 locus and rs10517 locus of NQO1 gene was genotyped via TaqMan assay, and the concentration of Oxidized low-density lipoprotein (ox-LDL) in the blood of the subjects was detected by enzyme linked immunosorbent assay (ELISA). The relationship between the polymorphism distribution and the susceptibility to ischemic stroke was evaluated.ResultsThe frequency distribution of the three genotypes of NQO1 rs1800566 between the case group and the control group was statistically significant, and cases carrying CT and TT genotype were less likely to suffer from ischemic stroke. Compared with individuals carrying T allele, C allele carriers have higher risk of ischemic stroke. However, there was no significant difference in frequency distribution among the three genotypes of NQO1 rs10517 between controls and patients.ConclusionThe NQO1 rs1800566 C allele may be a novel marker associated with ischemic stroke susceptibility in Chinese Han population. Polymorphism of rsl800566 locus in NQO1 gene may be protective against ischemic stroke risk.

Tuberculosis and Risk of Ischemic Stroke: A Nationwide Cohort Study

Conflicting results exist regarding the risk of ischemic stroke in tuberculosis survivors. We aimed to estimate the risk of ischemic stroke using a nationwide population-based retrospective cohort. We gathered data from the Korean National Health Insurance Service on tuberculosis survivors and 1:1 age- and sex-matched non-tuberculosis cases. Eligible participants were followed up from 1 year after tuberculosis diagnosis to the date of ischemic stroke event, date of death, or until the end of the study period (December 31, 2018), whichever came first. Cox proportional hazard regression and stratified analyses were performed to identify any related factors. During follow-up periods of 3.8 years for patients with tuberculosis and matched non-tuberculosis cases, 1.3% of patients with tuberculosis (941/72 863) and 1.0% of matched non-tuberculosis cases (707/72 863) developed ischemic stroke. The overall risk of ischemic stroke was higher in tuberculosis patients (adjusted hazard ratio: 1.22 [95% CI, 1.10-1.36]) compared with the matched non-tuberculosis cases. A stratified analysis showed that patients with tuberculosis had increased risk of ischemic stroke regardless of age, sex, smoking status, alcohol consumption, physical activity, body mass index, and Charlson Comorbidity Index score. Tuberculosis survivors had a higher risk of ischemic stroke than their matched non-tuberculosis cases. The results of this study suggest that tuberculosis is a crucial infectious factor associated with increased incidence of ischemic stroke.

Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study

Background and aimsIndividuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. MethodsThis prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. ResultsIndividuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. ConclusionsNo significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti-thrombotic medication.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair.

BackgroundWe sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement.Methods and ResultsTwo atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55–0.82], P<0.001), ischemic stroke (HR, 0.72 [95% CI, 0.52–1.00], P=0.05) and bleeding (HR, 0.79 [95% CI, 0.63–0.99], P=0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow‐up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86–1.01], P=0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13–1.43], P<0.001), and lower risk of bleeding (adjusted HR, 0.86 [95% CI, 0.80–0.93], P<0.001) compared with warfarin.ConclusionsIn patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study.

SummaryBackgroundEpoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that may impact atherosclerosis, and animal experimental studies suggest EETs protect cardiac function. Plasma EETs are mostly esterified to phospholipids and part of an active pool. To address the limited information about EETs and CVD in humans, we conducted a prospective study of total plasma EETs (free + esterified) and diabetes-related CVD in the Cardiovascular Health Study (CHS).MethodsWe measured 4 EET species and their metabolites, dihydroxyepoxyeicosatrienoic acids (DHETs), in plasma samples from 892 CHS participants with type 2 diabetes. We determined the association of EETs and DHETs with incident myocardial infarction (MI) and ischemic stroke using Cox regression.FindingsDuring follow-up (median 7.5 years), we identified 150 MI and 134 ischemic strokes. In primary, multivariable analyses, elevated levels of each EET species were associated with non-significant lower risk of incident MI (for example, hazard ratio for 1 SD higher 14,15-EET: 0.86, 95% CI: 0.72–1.02; p=0.08). The EETs-MI associations became significant in analyses further adjusted for DHETs (hazard ratio for 1 SD higher 14,15-EET adjusted for 14,15-DHET: 0.76, 95% CI: 0.63–0.91; p=0.004). Elevated EET levels were associated with higher risk of ischemic stroke in primary but not secondary analyses. Three DHET species were associated with higher risk of ischemic stroke in all analyses.InterpretationFindings from this prospective study complement the extensive studies in animal models showing EETs protect cardiac function and provide new information in humans. Replication is needed to confirm the associations.FundingUS National Institutes of Health.