Risk Of Ischemic Stroke In Patients Research Articles

The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design

IntroductionLeft atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE. MethodsLeft Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism. ConclusionThe results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF. Trial RegistrationClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1

A Clinical-Radiomics Nomogram for Predicting Early Ischemic Stroke Risk in Patients with Transient Ischemic Attack

To develop and validate a clinical-radiomics nomogram for predicting early ischemic stroke risk in patients who sustain a transient ischemic attack (TIA). A retrospective training dataset (n= 76) and a prospective validation dataset (n= 34) of patients with TIA were studied. Image processing was performed using ITK-snap and Artificial Intelligent Kit. Radiomics features were selected in R. A nomogram predicting recurrent TIA/stroke in 90 days as a recurrent ischemic event was established. Model performance was assessed by computing the receiver operating characteristic curve and decision curve analysis (DCA). We found a higher proportion of diabetes and hypertension in the patients with recurrent TIA compared with the stable patients in both the training and validation datasets (P < 0.05). Recurrent patients had significantly higher ABCD2 scores and plaque scores compared to stable patients. ABCD2 score and necrotic/lipid core area were independent risk factors for recurrent ischemic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.47-6.40; and OR, 1.20; 95% CI, 1.07-1.41, respectively). The radiomics model had area under the curve values of 0.737 (95% CI, 0.715-0.878) in the training dataset and 0.899 (95% CI, 0.706-0.936) in the validation dataset, which was superior to the ABCD2 score and plaque model for predicting stroke recurrence (P < 0.05). The nomogram predicting recurrent ischemic events was 0.923 (95% CI, 0.895-0.978) in the training dataset and 0.935 (95% CI, 0.830-0.959) in the validation dataset. DCA confirmed the clinical value of this nomogram. The nomogram, based on clinical ABCD2 score, carotid plaque components and radiomics score, shows good performance in predicting the risk of recurrent ischemic events in patients with TIA.

The Risk of Venous Thromboembolism and Ischemic Stroke Stratified by VTE Risk Following Multiple Myeloma: A Korean Population-Based Cohort Study.

Background: Multiple myeloma (MM) is associated with high morbidity and mortality, with elevated rates of arterial thrombosis and venous thromboembolism (VTE) and ischemic stroke (IS). We aimed to estimate the incidence of VTE and IS categorized by the VTE risk grade among individuals with MM in Korea. Additionally, we explored the potential of the IMPEDE VTE score as a tool for assessing IS risk in patients with MM. Methods: This retrospective cohort study comprised 37,168 individuals aged ≥ 18 years newly diagnosed with MM between January 2008 and December 2021 using the representative claims database of the Korean population. The risk of the incidence of VTE and IS within 6 months after MM diagnosis was stratified based on high-risk (IMPEDE VTE score ≥ 8) and low-risk (<8) categories. The hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The VTE incidence was 120.4 per 1000 person-years and IS incidence was 149.3 per 1000 person-years. Statistically significant differences were observed in the cumulative incidence rates of VTE between groups with high and low VTE scores (p < 0.001) and between individuals aged ≤ 65 years (p < 0.001) and those with a Charlson comorbidity index (CCI) ≥ 3 compared to lower scores (p < 0.001). Additionally, the cumulative incidence rate of IS differed significantly across all groups (p < 0.001). The HR for the high-risk group in VTE and IS occurrence was 1.59 (95% CI, 1.26-2.00) and 3.47 (95% CI, 2.99-4.02), respectively. Conclusions: It is important to screen and manage high-risk groups for the early development of VTE or IS in patients with newly diagnosed MM.

Statin use reduces radiation-induced stroke risk in advanced nasopharyngeal carcinoma patients

ObjectiveThis cohort study aimed to evaluate the impact of statin use on ischemic stroke risk in patients with advanced nasopharyngeal carcinoma (NPC) undergoing standard concurrent chemoradiotherapy (CCRT). MethodsUsing data from the Taiwan Cancer Registry Database, we conducted an inverse probability of treatment-weighted Cox regression analysis to examine the association between statin use during CCRT and ischemic stroke risk. ResultsThe adjusted hazard ratio (aHR) for ischemic stroke in the statin group compared to the non-statin group was 0.70 (95 % CI: 0.54–0.92; P < 0.0107). This protective effect was observed across different statin classes, with hydrophilic statins such as pravastatin showing an aHR of 0.37 (95 % CI: 0.17–0.85) and lipophilic statins including atorvastatin displaying an aHR of 0.32 (95 % CI: 0.21–0.50) compared to non-statin use. Analysis of cumulative defined daily doses (cDDD) revealed a dose–response relationship, with lower stroke risk observed in higher quartiles of cDDD. Additionally, patients with a daily defined dose (DDD) > 1 had a reduced risk of stroke with an aHR of 0.49 (95 % CI: 0.31–0.63), while those with DDD ≤ 1 showed an aHR of 0.59 (95 % CI: 0.40–0.84). ConclusionsOur study provides evidence supporting the beneficial effects of statin use during the CCRT period in reducing radiation-induced stroke risk among patients with advanced NPC undergoing definitive CCRT. Notably, pravastatin and atorvastatin demonstrated significant reductions in stroke occurrence. Furthermore, the findings suggest a dose–response relationship, where higher cumulative doses and greater daily dose intensity of statin use were associated with a lower risk of stroke.

Ischemic stroke risk factors not included in the CHADS-VASC score in patients with non-valvular atrial fibrillation.

In patients with atrial fibrillation, the CHA2DS2-VASC score guides stroke prevention using anticoagulants, but it is an imperfect score. Other potential risk factors such as renal failure, the type of atrial fibrillation, active smoking, cancer, sleep apnea or systemic inflammation have less well been investigated. To assess the impact of these factors on ischemic stroke risk in patients with non-valvular atrial fibrillation. On a population of 248 patients (124 patients with acute ischemic stroke and 124 controls), we performed a logistic regression to assess the impact of multiple non-classic risk factors for the prediction of acute ischemic stroke. Their impact on mortality was assessed by performing a survival analysis. A high CHA2DS2-VASc score (OR 1.75; 95% CI 1.13-2.70; p = 0.032), treatment with anticoagulants (OR 0.19; 95% CI 0.07-0.51; p < 0.001) and permanent atrial fibrillation (OR 6.31; 95% CI 2.46-16.19; p < 0.001) were independently associated with acute ischemic stroke. Renal failure and chronic obstructive pulmonary disease predicted a higher mortality. After adjusting for age, sex, the CHA2DS2-VASc score and the use of anticoagulants, the only risk factor predictive for acute ischemic stroke was the permanent type of AF (OR: 8.0 [95% CI 2.5-25.5], p < 0.001). The CHA2DS2-VASc score, the absence of anticoagulants and the permanent type of atrial fibrillation were the main predictive factors for the occurrence of acute ischemic stroke. Larger studies are necessary for conclusive results about other factors.

Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association.

Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27-CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65-CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590-CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90-CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Our stroke occurrence rate is consistent with other population-based reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox.

N-terminal pro-B-type natriuretic peptide and D-dimer combined with left atrial diameter to predict the risk of ischemic stroke in nonvalvular atrial fibrillation.

We aimed to explore the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP), d-dimer, and the echocardiographic parameter left atrial diameter (LAD) in identifying and predicting the occurrence of ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). We conducted a retrospective study of 445 patients with NVAF in the First Affiliated Hospital of Nanchang University. They were divided into the NVAF (309 cases) and NVAF with stroke (136 cases) groups according to whether acute ischemic stroke (AIS) occurred at admission. Multivariate logistic regression was used to analyze the odds ratio (OR) of NT-proBNP, d-dimer, and LAD for IS. The predictive value of NT-proBNP, d-dimer, and LAD in identifying the occurrence of IS in NVAF was determined by plotting the receiver operating characteristic (ROC) curves. NT-proBNP, d-dimer, and LAD levels were significantly higher in the NVAF with stroke group than in the NVAF group (p < .05). NT-ProBNP, d-dimer, and LAD were independently associated with IS in NVAF patients (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.08-1.16; OR = 1.87, 95% CI: 1.37-2.55; OR = 1.21, 95% CI: 1.13-1.28, p < .01). The optimal cutoff points for NT-ProBNP, d-dimer, and LAD levels to distinguish the NVAF group from the NVAF with stroke group were 715.0 pg/ml, 0.515 ng/ml, and 38.5 mm, respectively, with the area under the curve (AUC) being [0.801 (95% CI: 0.76-0.84); 0.770 (95% CI: 0.72-0.85); 0.752 (95% CI: 0.71-0.80), p < .01]. The combined score of NT-proBNP, d-dimer, and LAD improved the predictive efficacy of the single index, with an AUC of 0.846 (95% CI: 0.81-0.88, p < .01), sensitivity of 77.2%, and specificity of 76.4%. NT-proBNP, d-dimer, and the echocardiographic parameter LAD have outstanding value in predicting the risk of IS in patients with NVAF.

Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting

BackgroundThe CHA2DS2‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long‐term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new‐onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2‐VASc scoring system for estimating the 1‐year ischemic stroke risk in patients with new‐onset postoperative atrial fibrillation after coronary artery bypass grafting.Methods and ResultsAll patients with new‐onset postoperative atrial fibrillation and without oral anticoagulation after first‐time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry‐based observational cohort study. The 1‐year ischemic stroke rate at each step of the CHA2DS2‐VASc score was estimated using a Kaplan‐Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow‐up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2‐VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results.ConclusionsPatients with new‐onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2‐VASc score <3 have such a low 1‐year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.

Mental health conditions and risk of first-ever ischaemic stroke and death in patients with incident atrial fibrillation: A nationwide cohort study.

BackgroundAtrial fibrillation (AF) patients with mental health conditions (MHCs) have higher incidence of ischaemic stroke (IS) than patients without MHC, but whether this results from direct impact of MHCs or relates to higher prevalence of comorbidities and differences in the use of oral anticoagulant (OAC) therapy is unclear. We assessed the hypothesis that MHCs independently increase the risk of IS in patients with incident AF.MethodsThe nationwide FinACAF cohort covered all 203,154 patients diagnosed with incident AF without previous IS or transient ischaemic attack in Finland during 2007–2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC. The outcomes were first‐ever IS and all‐cause death.ResultsThe patients' (mean age 73.0 ± 13.5 years, 49.0% female) mean follow‐up time was 4.3 (SD 3.3) years and 16,272 (8.0%) experienced first‐ever IS and 63,420 (31.2%) died during follow‐up. After propensity score matching and adjusting for OAC use, no MHC group was associated with increased IS risk (adjusted SHRs (95% CI): depression 0.961 (0.857–1.077), bipolar disorder 1.398 (0.947–2.006), anxiety disorder 0.878 (0.718–1.034), schizophrenia 0.803 (0.594–1.085) and any MHC 1.033 (0.985–1.085)). Lower rate of OAC use partly explained the observed higher crude IS incidence in patients with any MHC. Depression, schizophrenia and any MHC were associated with higher all‐cause mortality (adjusted HRs [95% CI]: 1.208 [1.136–1.283], 1.543 [1.352–1.761] and 1.149 [1.116–1.175], respectively).ConclusionsIn this nationwide retrospective cohort study, MHCs were not associated with the incidence of first‐ever IS in patients with AF.

Infarct on Brain Imaging, Subsequent Ischemic Stroke, and Clopidogrel-Aspirin Efficacy

In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, acute treatment with clopidogrel-aspirin was associated with significantly reduced risk of recurrent stroke. There may be specific patient groups who are more likely to benefit from this treatment. To investigate whether the association of clopidogrel-aspirin with stroke recurrence in patients with minor stroke or high-risk transient ischemic attack (TIA) is modified by the presence of infarct on imaging attributed to the index event (index imaging) among patients enrolled in the POINT Trial. In the POINT randomized clinical trial, patients with high-risk TIA and minor ischemic stroke were enrolled at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand from May 28, 2010, to December 19, 2017. In this post hoc analysis, patients were divided into 2 groups according to whether they had an acute infarct on index imaging. All POINT trial participants with information available on the presence or absence of acute infarct on index imaging were eligible for this study. Univariable Cox regression models evaluated associations between the presence of an infarct on index imaging and subsequent ischemic stroke and evaluated whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Data were analyzed from July 2020 to May 2021. Presence or absence of acute infarct on index imaging. The primary outcome is whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Of the 4881 patients enrolled in POINT, 4876 (99.9%) met the inclusion criteria (mean [SD] age, 65 [13] years; 2685 men [55.0%]). A total of 1793 patients (36.8%) had an acute infarct on index imaging. Infarct on index imaging was associated with ischemic stroke during follow-up (hazard ratio [HR], 3.68; 95% CI, 2.73-4.95; P < .001). Clopidogrel-aspirin vs aspirin alone was associated with decreased ischemic stroke risk in patients with an infarct on index imaging (HR, 0.56; 95% CI, 0.41-0.77; P < .001) compared with those without an infarct on index imaging (HR, 1.11; 95% CI, 0.74-1.65; P = .62), with a significant interaction association (P for interaction = .008). In this study, the presence of an acute infarct on index imaging was associated with increased risk of recurrent stroke and a more pronounced benefit from clopidogrel-aspirin. Future work should focus on validating these findings before targeting specific patient populations for acute clopidogrel-aspirin treatment.

Construction and evaluation of a model for predicting ischemic stroke risk in patients with sudden sensorineural hearing loss

Objective:To explore the related factors of sudden sensorineural hearing loss complicated with ischemic stroke, construct the risk prediction model, and verify the prediction effect of the model. Methods:A retrospective analysis was performed on 901 sudden sensorineural hearing loss patients hospitalized from January 2017 to December 2020, The patients were divided into the ischemic stroke group（100 cases） and the sudden deafness group（801 cases） according to whether they were complicated with ischemic stroke, The independent correlation factors of sudden deafness complicated with ischemic stroke were screened by univariate analysis and multivariate Logistic regression model, and the risk prediction model and internal verification were established. The original data were randomly divided into the modeling group（631 cases） and the validation group（270 cases） at a 7∶3 ratio. Hosmer-Lemeshow and receiver operating characteristic curve were used to test the goodness of fit and predictive effect of the model, and 270 patients were included again in the application research of the model and to test the prediction effect of the model. Results:The results of single factor analysis showed that age, NEUR, NC, NLR, PLR, TC, HDL-C, BUN, TC-HDL-C, TG/HDL-C, LDL-C/HDL-C, Hcy, FIB and cervical vascular plaque were related factors of sudden sensorineural hearing loss complicated with ischemic stroke（P<0.05）. Age（OR=2.816）, NEUR（OR=2.707）, Hcy（OR=88.833）, FIB（OR=1.389）, TC-HDL-C（OR=1.613）, cervical vascular plaque（OR=2.862） are the independent risk factors of SNHL complicated with ischemic stroke. These 6 factors are used to construct a prediction model. Hosmer-lemeshow test results, the area under the ROC curve of the modeling group was 0.846, P=0.555, Youden index was 0.564, sensitivity was 0.820, and specificity was 0.744. In the validation group, the area under ROC curve was 0.847, P=0.288, Youden index was 0.432, sensitivity was 0.783, and specificity was 0.649. Conclusion:The risk prediction model constructed in this study shows good prediction efficiency. which can provide references for the clinical screening of ischemic stroke risks in patients with sudden sensorineural hearing loss and early interventions in early stage.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

CHA2DS2-VASc below 3 predicts low one-year ischemic stroke risk in postoperative atrial fibrillation after CABG

Abstract Background Ischemic stroke prevention is a major goal in patients with atrial fibrillation (AF). Neither the optimal risk assessment method, nor the risk-benefit-ratio of long-term use of oral anticoagulation (OAC) is, however, known in patients with new-onset AF (POAF) after cardiac surgery. Purpose To explore the feasibility of using the CHA2DS2-VASc scoring system in predicting the one-year ischemic stroke risk in patients with POAF after coronary artery bypass grafting (CABG). Methods All patients in Sweden with POAF after isolated CABG 2007–2017, with at least one year of follow-up, and without oral anticoagulation (OAC), were included in this observational, registry-based cohort study. POAF was defined as any new-onset AF during the index hospitalization for CABG. Primary endpoint was the one-year ischemic stroke risk at each step of the CHA2DS2-VASc score in POAF patients with at least one-year follow-up. Results Out of 6368 POAF patients without OAC neither at hospital discharge nor before the occurrence of events, 4467 (70.1%) had at least one year follow-up with altogether 124 ischemic strokes within one year from discharge. The one-year risk for ischemic stroke was &amp;lt;1% for a CHA2DS2-VASc score &amp;lt;3, 1–2% for a CHA2DS2-VASc score 3, and &amp;gt;2% for a CHA2DS2-VASc score ≥4. The area under the receiver-operating-characteristic curve for predicting ischemic stroke was 0.67 (95% CI 0.64–0-69). Conclusions The CHA2DS2-VASc score was suitable for predicting low risk for ischemic stroke during the first year after hospital discharge in patients with POAF after CABG. A risk &amp;lt;1% considered low was, however, observed at a considerably higher score than in patients with non-surgical/non-valvular AF described in previous studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation (grant 20150587 and 20180560 to Anders Jeppsson)Region Västra Götaland (grant VGFOUREG-847811 to Anders Jeppsson and grant VGFOUREG-648981 to Amar Taha) Event rates during one year

Risk of Ischemic Stroke in Asymptomatic Atrial Fibrillation Incidentally Detected in Primary Care Compared with Other Clinical Presentations.

It is uncertain whether stroke risk of asymptomatic ambulatory atrial fibrillation (AA-AF) incidentally detected in primary care is comparable with other clinical AF presentations in primary care or hospital. The stoke risk of 22,035 patients with incident nonvalvular AF from the United Kingdom primary care Clinical Practice Research Datalink with linkage to hospitalization and mortality data was compared with 23,605 controls without AF (age- and sex-matched 5:1 to 5,409 AA-AF patients). Incident AF included 5,913 with symptomatic ambulatory AF (SA-AF); 4,989 with primary and 5,724 with nonprimary hospital AF discharge diagnosis (PH-AF and non-PH-AF); and 5,409 with AA-AF. Ischemic stroke adjusted subhazard ratios (aSHRs) within 3 years of AA-AF were compared with SA-AF, PH-AF, non-PH-AF, and no AF, accounting for mortality as competing risk and adjusted for ischemic stroke risk factors. There were 1,026 ischemic strokes in 49,544 person-years in patients with incident AF (crude incidence rate: 2.1 ischemic strokes/100 person-years). Ischemic stroke aSHR over 3 years showed no differences between AA-AF and SA-AF, PH-AF, and non-PH-AF groups (aSHR: 0.87-1.01 vs. AA-AF). All AF groups showed a significantly higher aSHR compared with no AF. Ischemic stroke risk in patients with AA-AF incidentally detected in primary care is far from benign, and not less than incident AF presenting clinically in general practice or hospital. This provides justification for identification of previously undetected AF, e.g., by opportunistic screening, and subsequent stroke prevention with thromboprophylaxis, to reduce the approximately 10% of ischemic strokes related to unrecognized AF.

Statins, Risk of Death and Ischemic Stroke in Patients with Dementia: A Registry-Based Observational Cohort Study.

Survival in patients with dementia is variable. Statins are a cornerstone of cardiovascular prevention. However, the effect of statins on mortality and risk for stroke in patients with dementia is not clear. The aim of the study was to analyse the association between the use of statins and the risk of all-cause death and first ischemic stroke in patients diagnosed with dementia. A longitudinal cohort study of 48 771 patients based on combined Swedish registries was conducted. The association between the incident use of statins one year prior to dementia diagnosis, allcause mortality and first ischemic stroke was examined using propensity score-matched flexible parametric or Cox hazard survival models and is presented with hazard ratios and corresponding 95% confidence intervals. After propensity score matching, incident users of statins (n=1412) had a lower risk of all-cause death (HR 0.82, 95% CI 0.74-0.91) and ischemic stroke (HR 0.62, 95% CI 0.43-0.89) compared to matched non-users (n=4482). In stratified analysis, the protective association between incident statin use and survival was observed in men, patients older than 75 years, with Alzheimer's disease and vascular dementia. Furthermore, we observed a protective association between incident use of statins and first ischemic stroke risk in men, patients older than 75 years and with mixed dementia. There was a graded association between cumulative doses of statins and mortality. The use of statins might be beneficial for the survival and ischemic stroke risk in patients with dementia in a dose-dependent manner.

Relationship of aging and incident comorbidities to stroke risk in 594,169 Patients with atrial fibrillation: a nationwide analysis

Abstract Background When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities. This study hypothesized that the “Delta CHA2DS2-VASc score”, which reflects the change in score between baseline and follow-up, may be predictive of ischemic stroke compared with the baseline or follow-up assessments of the CHA2DS2-VASc score. Methods Based on the France nationwide administrative hospital-discharge database, we collected information for all patients treated with AF between 2010 and 2019 in France. Adverse outcomes were investigated during follow-up. A total of 594,169 patients with AF who did not have comorbidities of the CHA2DS2-VASc score except for age and sex, were studied. The Delta CHA2DS2-VASc score was defined as the change/difference between the baseline and follow-up CHA2DS2-VASc scores. During 1,290,721 person-years, 19,492 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were analysed and compared. Results The mean baseline CHA2DS2-VASc score was 1.69, which increased to 2.33 during the follow-up, with a mean Delta CHA2DS2-VASc score of 0.64. The CHA2DS2-VASc score increased in 39.8% of patients. Among 19,492 patients who experienced ischemic stroke, 66.0% had a Delta CHA2DS2-VASc score ≥1 compared with only 38.9% in patients without ischemic stroke, and 5,811 (29.8%) patients had ≥2 new-onset comorbidity, the most common being hypertension. The follow-up CHA2DS2-VASc score and Delta CHA2DS2-VASc score were significant predictors of ischemic stroke (C-index 0.670 95% CI 0.667–0.674 and 0.637 95% CI 634–641 respectively) that performed better than baseline CHA2DS2-VASc score (C-index 0.613 95% CI 0.609–0.616, p&amp;lt;0.0001 for DeLong test). Conclusions In this AF cohort, we found that stroke risk (CHA2DS2-VASc score) was non-static, and that many patients developed ≥1 new stroke risk factor(s) before presentation with ischemic stroke. The follow-up CHA2DS2-VASc score and its change (ie Delta CHA2DS2-VASc, reflecting the change in stroke risk profile between baseline and follow-up) were better predictors of ischemic stroke than relying on the baseline CHA2DS2-VASc score. This emphasises how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities, and regular re-assessment of risk is needed. Funding Acknowledgement Type of funding source: None

Are all CHA2DS2-VASc risk factors created equal? An assessment of stroke risk among 34,470 patients with CHA2DS2-VASc scores of 1 or 2

Abstract Introduction The CHA2DS2-VASc score is commonly used to assess ischemic stroke risk in patients with documented atrial fibrillation (AF). Whether each combination of CHA2DS2-VASc score 1 or 2 confers a similar stroke risk is poorly understood. Methods A de-identified database of aggregated electronic health record (EHR) data from 2007–2017 was used to identify patients not on oral anticoagulation (OAC) who had documented AF and CHA2DS2-VASc scores of 1 or 2. CHA2DS2-VASc=1 groups included patients with only heart failure, hypertension, age 65–74, diabetes, vascular disease or female gender. The 17 possible permutations of CHA2DS2-VASc =2 scores were consolidated into 6 groups: prior stroke/TIA, age &amp;gt;75, 2 co-morbidities, 1 co-morbidity + age 65–74, 1 co-morbidity + female gender, or age 65–74 + female gender. Stroke risk hazard ratios were computed for each of these groups. Results A total of 34,470 patients (61.0±12.0 years, 67.3% male) not on OAC with a documented history of AF and CHA2DS2-VASc scores of 1 (n=16,572) or 2 (n=17,898) were identified. The annual risks of ischemic stroke among CHA2DS2-VASc 1 and 2 patients were 0.22% [0.18–0.26] and 0.38% [0.33–0.43], respectively. For CHA2DS2-VASc =1 patients, age 65–74 conferred a greater risk of stroke while female gender conferred a lower risk. For CHA2DS2-VASc =2 patients, prior stroke/TIA conferred a greater risk of stroke while 1 co-morbidity + female gender conferred a lower risk [Figure]. Conclusion Ischemic stroke risk varies significantly across specific risk factors in patients with CHA2DS2-VASc scores =1 or 2. Therefore, OAC decisions in these patients should consider individual risk factors rather than the aggregate score alone. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic

Adjunctive Chinese Herbal Products Therapy Reduces the Risk of Ischemic Stroke Among Patients With Rheumatoid Arthritis.

We performed a retrospective cohort study to investigate the association between the risk of ischemic stroke (IS) and the use of Chinese herbal products (CHP) in combination with western medicine (WM) among patients with rheumatoid arthritis (RA). The data were sourced from the registry for beneficiaries, inpatient and ambulatory care claims, and Registry for Catastrophic Illness from the National Health Insurance Research Database (NHIRD) in Taiwan between 1997 and 2011. Patients, who were newly diagnosed with RA between 1997 and 2010, were classified as the CHP group or non-CHP group depending on the presence of absence the adjunctive use of CHP following a diagnosis of RA. A total of 4,148 RA patients were in both the CHP and non-CHP groups after 1:1 matching. Patients in the CHP group had a significantly lower risk of IS compared to patients in the non-CHP group (adjusted hazard ratio [aHR], 0.67; 95% confidence interval [CI], 0.52–0.86). In the CHP group, patients who used CHP for more than 30 days had a lower risk of IS than their counterparts (aHR: 0.61, 95% CI: 0.40–0.91). Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Shu-Jin-Huo-Xie-Tang, and Du-Huo-Ji-Sheng-Tang might be associated with a lower risk of IS. Finally, the use of CHP in combination with WM was associated with a decreased risk of IS in patients with RA, especially among those who had used CHP for more than 30 days. A further randomized control trial is required to clarify the casual relationship between these results.

Associations of MTRR A66G polymorphism and promoter methylation with ischemic stroke in patients with hyperhomocysteinemia.

Patients with hyperhomocysteinemia (HHcy) have a higher risk of developing ischemic stroke (IS). The association between MTRR A66G polymorphism and promoter methylation with IS in patients with HHcy is also uncertain. The present study aimed to investigate the association between the MTRR polymorphism and methylation with IS in HHcy patients. This case-control study included a total of 304 HHcy patients (95 with IS and 209 without IS). Multivariate logistic regression analyses were applied to explore the association between MTRR polymorphism and classical atherothrombotic risk factors with the risk of IS. The log-additive and dominant models were markedly different in participants with IS compared to the control group (p = 0.031 and 0.016, respectively). The log-additive and dominant showed a significant association with IS in the low level plasma homocysteine groups (p = 0.024 and 0.014, respectively). No significant difference of methylation between IS and without IS group (p > 0.05). Patients with high plasma homocysteine had a 4.041-4.941 fold higher risk of IS (p = 0.01, 0.016 and 0.041, respectively) compared to the low plasma homocysteine group. Age, diabetes, hypertension and plasma homocysteine were the risk factors for IS in patients with HHcy (p = 0.033, 0.000, 0.001 and 0.038, respectively). MTRR A66G polymorphism and an elevated plasma plasma homocysteine level were significantly associated with an increased risk of IS in patients with HHcy. Age, diabetes, hypertension and Hcy were all found to be associated with IS.

Ischemic stroke risk during post-discharge phases of heart failure: association of left ventricular concentric geometry.

Despite a higher risk of ischemic stroke in hospitalized patients with acute heart failure (HF), little is known about the risk of ischemic stroke during the post-discharge phases of HF. Here we investigated (1) the ischemic stroke incidence rate during the post-discharge phases among HF patients receiving standard treatments; (2) the association between ischemic stroke incidence and clinical background, including cardiac structure and function. Among 950 patients who required hospitalization for HF (median duration: 19 days) at our institution, where they received standard treatments, we investigated stroke occurrences during the 2-year period following their discharge and retrospectively evaluated their clinical data. Relative wall thickness (RWT) and left ventricular (LV) mass were determined based on echocardiographic measurements and then used to determine LV geometric patterns. During the follow-up period, ischemic stroke occurred in 25 patients (2.6%) after hospital discharge (1.4 per 100 patient-years). The incidence rate of IS tended to be higher in patients with AF than those without AF (1.8 vs. 1.0 per 100 patient-years, respectively). Notably, multivariate analysis revealed a significant association between RWT and ischemic stroke risk (p < 0.05). RWT was associated with ischemic stroke risk in patients with AF or left atrial enlargement, but not in patients without them. These findings suggest that even with standard HF treatments, the risk of ischemic stroke is high in patients with HF. Moreover, LV concentric geometry is a significant risk factor for ischemic stroke in patients with HF, especially in those with left atrial remodeling and/or AF.