Elevated Risk Of Ischemic Stroke Research Articles

Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1β risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1β, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1β, IL-6, and IL-17.

Causal associations between gut microbiota, gut microbiota-derived metabolites, and cerebrovascular diseases: a multivariable Mendelian randomization study.

Mounting evidence has demonstrated the associations between gut microbiota, gut microbiota-derived metabolites, and cerebrovascular diseases (CVDs). The major categories of CVD are ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). However, the causal relationship is still unclear. A two-sample Mendelian randomization (MR) study was conducted leveraging the summary data from genome-wide association studies. The inverse variance-weighted, maximum likelihood, weighted median, and MR.RAPS methods were performed to detect the causal relationship. Several sensitivity analyses were carried out to evaluate potential horizontal pleiotropy and heterogeneity. Finally, reverse MR analysis was conducted to examine the likelihood of reverse causality, and multivariable MR was performed to adjust the potential confounders. We collected 1,505 host single nucleotide polymorphisms (SNPs) linked to 119 gut microbiota traits and 1,873 host SNPs associated with 81 gut metabolite traits as exposure data. Among these, three gut bacteria indicated an elevated risk of IS, two of ICH, and one of SAH. In contrast, five gut bacteria were associated with a reduced risk of IS, one with ICH, and one with SAH. Our study also demonstrated the potential causal associations between 11 gut microbiota-derived metabolites and CVD. This study provided evidence of the causal relationship between gut microbiota, gut microbiota-derived metabolites, and CVD, thereby offering novel perspectives on gut biomarkers and targeted prevention and treatment for CVD.

Functional polymorphism in miR-208 is associated with increased risk for ischemic stroke

BackgroundThe miR-208 gene is one of the microRNAs now under active studies, and has been found to play significant roles in an array of cardiovascular diseases. Nevertheless, until now, no studies have examined the relationship between the susceptibility to ischemic stroke (IS) and genetic variations in miR-208. This study explored the association between the miR-208 polymorphisms (rs178642, rs8022522, and rs12894524) and the risk of IS.MethodsA total of 205 cases of IS and 211 control subjects were included. The SNPscans genotyping test was employed to determine the genotypes of the three polymorphisms.ResultsSignificant correlation was observed between rs8022522 polymorphism and risk of IS on the basis of analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 2.159, 95% CI: 1.052–4.430, P = 0. 036; AA vs. GG: adjusted OR = 5.154, 95% CI: 1.123–23.660, P = 0.035; dominant model: adjusted OR = 1.746, 95% CI, 1.075–2.838, P = 0.025; G vs. A: adjusted OR = 2.451, 95% CI: 1.374–4.370, P = 0.002).ConclusionsThe rs8022522 polymorphism of the miR-208 gene is significantly associated with an elevated risk of ischemic stroke in Chinese.

Incidence of Ischemic Stroke in US Veterans Living with Spinal Cord Injury: Preliminary Data (S3.005)

<h3>Objective:</h3> In this preliminary study, we estimate the 4-year incidence of ischemic stroke and associated risk factors in United States (US) Veterans living with spinal cord injuries and disorders (SCI/D). <h3>Background:</h3> People with SCI/D have been reported to have an elevated risk of ischemic stroke, based on a study in the population of Taiwan [Wu et al, Neurology. 2012;78:1051–1057]. This prior study reported a cumulative incidence rate of ischemic stroke of 1.9% over 4 years subsequent to SCI, vs 0.6% in matched non-injured controls. <h3>Design/Methods:</h3> We used Department of Veterans Affairs (VA) administrative databases to examine the incidence of ischemic stroke between fiscal years 2018–2021. Veterans living with strokes were identified using ICD-9 or 10 codes for cerebral infarction or sequelae of cerebral infarction. Veterans with diagnoses of ischemic strokes or sequelae during 2013–2017 were excluded. Statistical analyses included frequencies and multiple regression models. <h3>Results:</h3> From FY 2018–2021, 394 of 12,547 Veterans living with SCI had a newly-recorded ischemic stroke, reflecting a 4-year incidence of 3.14%, and an average annual incidence of 0.79%. Compared to Veterans with a D injury classification by the American Spinal Injury Association (ASIA) Impairment Scale, Veterans with high tetraplegia had a higher likelihood of ischemic stroke (IRR=1.91, 95% CI: 1.37 – 2.67). Compared to Veterans with traumatic SCI, Veterans with non-traumatic SCI/D also had a higher likelihood of ischemic stroke (IRR = 1.43, 95% CI: 1.13 – 1.80). <h3>Conclusions:</h3> US Veterans with SCI/D have a higher incidence of ischemic stroke than that reported for the Taiwanese population with SCI. Tetraplegia and a non-traumatic injury etiology seem to be SCI-centric risk factors. Further study will include comparison of stroke incidence to that of age- and sex-matched US Veterans without SCI. <b>Disclosure:</b> The institution of Dr. Willenberg has received research support from Dept of Veterans Affairs. The institution of Dr. Smith has received research support from Dept of Veterans Affairs . Kevin Stroupe has received research support from Department of Veterans Affairs. Dr. Sippel has nothing to disclose. Zhiping Huo has nothing to disclose. Dr. Sabharwal has received publishing royalties from a publication relating to health care.

Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020

Undertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin. To systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions. This retrospective cohort study uses administrative claims data from Optum's Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022. Coexisting dementia, frailty, and anemia. The primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as <80% of proportion of days covered among patients newly started on OAC in each year). There were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients). Since the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.

Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Variation With Susceptibility of Patients With Ischemic Stroke: A Meta-Analysis.

Discovery and validation of genetic factors for multifactorial and polygenic disorders like stroke are needed to make progress in precision medicine. Although some traditional risk factors for stroke have been identified, they do not fully explain the pathophysiological mechanism of ischemic stroke. The research of genetic risk factors is becoming increasingly relevant in the understanding of stroke mechanisms and the finding of population-specific therapeutic targets. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine metabolism, and a high homocysteine level is a risk factor for stroke. Using a meta-analysis technique, we investigated the link between the MTHFR C677T gene polymorphism and the risk of ischemic stroke.We used the electronic databases PubMed, Medline, Embase, and Google Scholar to find articles in the Journal of Stroke. If heterogeneity was more than 50%, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model; otherwise, a fixed-effects model was used.A total of 67 case-control studies with 17,704 cases and 21,981 controls met our inclusion criteria. The Asian population was represented by 41 studies, whereas the Caucasian population was represented by 26. Under the recessive model, a gene polymorphism at the 677 location of the MTHFR gene is related to an elevated risk of ischemic stroke (OR: 1.29, 95% CI: 1.22-1.37, P < 0.001).People who have the MTHFR C677T gene polymorphism have a greater risk of stroke than people who do not.

Unfavorable Dietary Quality Contributes to Elevated Risk of Ischemic Stroke among Residents in Southwest China: Based on the Chinese Diet Balance Index 2016 (DBI-16).

Background: Little is known about the effects of dietary quality on the risk of ischemic stroke among Southwest Chinese, and evidence from prospective studies is needed. We aimed to evaluate the associations of ischemic stroke with dietary quality assessed by the Chinese Diet Balance Index 2016 (DBI-2016). Methods: The Guizhou Population Health Cohort Study (GPHCS) recruited 9280 residents aged 18 to 95 years from 12 areas in Guizhou Province, Southwest China. Baseline investigations, including information collections of diet and demographic characteristics, and anthropometric measurements were performed from 2010 to 2012. Dietary quality was assessed by using DBI-2016. The primary outcome was incident ischemic stroke diagnosed according to the International Classification of Diseases 10th revision (ICD-10) until December 2020. Data analyzed in the current study was from 7841 participants with complete information of diet assessments and ischemic stroke certification. Cox proportional hazards models were used to estimate the risk of ischemic stroke associated with dietary quality. Results: During a median follow-up of 6.63 years (range 1.11 to 9.53 years), 142 participants were diagnosed with ischemic stroke. Participants with ischemic stroke had a more excessive intake of cooking oils, alcoholic beverages, and salt, and had more inadequacy in meats than those without ischemic stroke. (p < 0.05). Compared with participants in the lowest quartile (Q1), those in the highest quartile (Q4) of the higher bound score (HBS) and of the dietary quality distance (DQD) had an elevated risk for ischemic stroke, with the corresponding hazard ratios (HRs) of 3.31 (95%CI: 1.57–6.97) and 2.26 (95%CI: 1.28–4.00), respectively, after adjustment for age, ethnic group, education level, marriage status, smoking and waist circumference, and the medical history of diabetes and hypertension at baseline. In addition, excessive intake levels (score 1–6) of cooking oils, excessive intake levels (score 1–6) of salt, and inadequate intake levels (score −12 to −7) of dietary variety were positively associated with an increased risk for ischemic stroke, with the multiple HRs of 3.00 (95%CI: 1.77–5.07), 2.03 (95%CI: 1.33–3.10) and 5.40 (95%CI: 1.70–17.20), respectively. Conclusions: Our results suggest that unfavorable dietary quality, including overall excessive consumption, excessive intake of cooking oils and salt, or under adequate dietary diversity, may increase the risk for ischemic stroke.

Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding: A Danish population‐based cohort study

ObjectivesWe examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). MethodsThis population‐based cohort study used data from Danish health registries. We identified all patients with a first‐time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person‐years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA2DS2VASc score, and Charlson Comorbidity Index score. ResultsWe identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow‐up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1‐1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2‐2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7–1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1‐2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1‐4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3–2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7–3.9). ConclusionIn patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications.

Abstract TP225: Socioeconomic Status And Etiologies Of Ischemic Stroke In Peru

Background: Studies have reported an association between lower socioeconomic status (SES) and an elevated risk of ischemic stroke. It is unclear whether low SES is correlated with a specific etiology of ischemic stroke. Few studies have investigated the relationship in LMIC nations with wide disparities in SES. We analyzed data from a hospital-based stroke registry in Lima, Peru to determine the association between level of education as an indicator of SES and ischemic stroke etiology. Methods: All patients hospitalized with ischemic stroke at the National Institute of Neurologic Sciences from 2015-2018 were prospectively collected in a registry including demographics, risk factors, highest attained level of education, and diagnosed etiology of stroke by TOAST criteria. Association between ordinal level of education and stroke etiology was assessed after adjusting for differences in demographics and comorbidities by a multinomial multivariate logistic regression model. Results: A total of 461 cases of ischemic stroke were ascertained with 38.4% female and a mean age of 66.2 (SD 13.0). Stroke etiology was composed of 7.5% atherosclerotic, 29.7% cardioembolic, 14.2% small vessel disease, 24.7% cryptogenic, and 24.0% with incomplete evaluation. Higher education level strata had more men, younger mean age, and lower rates of hypertension. After multivariate adjustment, lower level of education was associated with an increased odds of large artery atherosclerosis compared to all non-cardioembolic etiologies (OR=2.27; 95% CI, 1.12-4.55). There was no significant association with level of education and odds of cardioembolic stroke after multivariate adjustment. Conclusion: Lower SES is associated with an increased odds of atherosclerotic etiology in patients with non-cardioembolic ischemic stroke. The associated between SES and stroke may be attributed to a higher burden of atherosclerotic disease in lower SES.

Women With Osteoarthritis Are at Increased Risk of Ischemic Stroke: A Population-Based Cohort Study.

BackgroundOsteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan.MethodsWe identified 13,520 women with OA aged 20–99 newly diagnosed in 2000–2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort.ResultsThe incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09–1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37–2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24–4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin.ConclusionWomen with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients.

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients.Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity.Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, <40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially.Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

Contemporary review on the management of oral anticoagulation and anti-platelet therapies in patients undergoing percutaneous coronary intervention with concurrent atrial fibrillation

: Management of coronary artery disease (CAD) with percutaneous coronary intervention (PCI) in the setting of atrial fibrillation (AF) presents clinicians with the challenge of balancing thrombosis risk with bleeding risk. Major societies including American College of Cardiology (ACC)/American Heart Association (AHA), Heart Rhythm Society (HRS) and European Society of Cardiology (ESC) guideline recommendations include the necessity to use antiplatelet therapy and anticoagulation for the prevention of thromboembolism in patients who undergo intervention with PCI who have concurrent AF. Dual antiplatelet therapy (DAPT) is the standard of care for patients post PCI, and anticoagulation with vitamin K antagonists (VKA) or direct acting oral anticoagulants (DOAC) is the standard of care, with DOACS being recommended by ACC/AHA and ESC as preferred, for patients with AF and elevated ischemic stroke risk. Here, we review the contemporary major society guideline recommendations applicable for the use of triple therapy with dual anti-platelet agents and oral anticoagulant, in patients undergoing PCI who have concurrent AF. We also review and summarize the relevant historical primary literature related to the approval of antiplatelet and anticoagulant therapy in PCI and AF respectively. Using a case description as a basis to illustrate this difficult clinical scenario, we review the contemporary literature, and present proposed management algorithms.

Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China.

Background: Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene–cIMT interactions’ association with IS risk. Methods: A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records’ review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. Results: We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92–3.20) for IS and 2.75 (2.08–3.64) for LAA (both p trend <0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. Conclusions: Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.

Cerebrovascular risk factors associated with ischemic stroke in a young non-diabetic and non-hypertensive population: a retrospective case-control study

BackgroundGlobally, rates of ischemic stroke (IS) have been rising among young adults. This study was designed to identify risk factors associated with IS incidence in young adults unaffected by hypertension or diabetes.MethodsThis was a retrospective case-control study of early-onset IS patients without diabetes and hypertension. Control patients were matched with healthy individuals based upon sex, age (±2 years), and BMI (±3 kg/m2) at a 1:3 ratio. Sociodemographic, clinical, and risk factor-related data pertaining to these patients was collected. The association between these risk factors and IS incidence was then assessed using conditional logistic regression models.ResultsWe recruited 60 IS patients and 180 controls with mean ages of 44.37 ± 4.68 and 44.31 ± 4.71 years, respectively, for this study. Relative to controls, IS patients had significantly higher total cholesterol (TG), homocysteine (HCY), white blood cell (WBC), absolute neutrophil count (ANC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, and significantly lower high-density lipoprotein cholesterol (HDL-C) and triglyceride cholesterol (TC), free triiodothyronine (FT3), and free thyroxine (FT4) levels (all P < 0.05). After controlling for potential confounding factors, HCY and ANC were found to be significantly positively associated with IS incidence (OR 1.518, 95%CI 1.165–1.977, P = 0.002 and OR 2.418, 95%CI 1.061–5.511, P = 0.036, respectively), whereas HDL-C and FT3 levels were negatively correlated with IS incidence (OR 0.001, 95%CI 0.000–0.083, P = 0.003 and OR 0.053, 95%CI 0.008–0.326, P = 0.002, respectively).ConclusionsIn young non-diabetic and non-hypertensive patients, lower HDL-C and FT3 levels and higher HCY and ANC levels may be associated with an elevated risk of IS. Additional prospective studies of large patient cohorts will be essential to validate these findings.

J-shaped relationship between serum uric acid levels and the risk of ischemic stroke in high-risk individuals: A hospital-based observational study

ObjectiveThe relationship between serum uric acid (SUA) and the risk of ischemic stroke (IS) has been fully elucidated in previous studies. Therefore, we further investigated the relationship between SUA levels and the risk of IS. Patients and methods2195 patients at the Beijing Hospital, between February 2012 and May 2018, were enrolled in our hospital-based cross-sectional study. The patients were divided into an IS group and a (non-IS) control group, based on their medical records. SUA level was measured using the enzymatic uricase method. Univariate and multivariable logistic regression models were used for the analysis. ResultsA total of 300 patients with IS [176 men; age (mean ± SD): 71.38 ± 10.66 years] and 1895 control patients [1060 men; age (mean ± SD): 66.12 ± 12.04 years] were enrolled in this study. IS patients had higher concentrations of SUA, compared with control group patients [6.11 ± 1.92 vs. 5.77 ± 1.62 (mg/dL)]; P = 0.004). We observed a J-shaped association between SUA levels and the risk of IS. Both the univariate and multivariate logistic regression analyses found a significantly elevated risk of IS in the bottom and upper SUA levels both in quartiles and deciles, compared with the intermediate SUA levels. ConclusionThese results indicate a J-shaped, independent association between SUA levels and the risk of IS in high-risk individuals.

Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke

Background: The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations.Aim: To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population.Methods: In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method.Results: The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12–3.20), p = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25–2.32), p = 0.002).Conclusion: Consequently, our data demonstrate contribution of MTHFR variants in risk of ischemic stroke in Iranian population.

Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese Adults.

In observational studies, type 2 diabetes is associated with two- to fourfold higher risk of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank (CKB), we examined associations of genetically predicted type 2 diabetes with CVD among ∼160,000 participants to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (odds ratio 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n = 6,819) and elevated risk of ischemic stroke (IS) (1.08 [1.02, 1.14]; n = 17,097), nonlacunar IS (1.09 [1.03, 1.16]; n = 13,924), and major coronary event (1.12 [1.02, 1.23]; n = 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n = 3,173) or intracerebral hemorrhage (ICH) (1.01 [0.94, 1.10], n = 6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (P for heterogeneity >0.3) and with the associations of type 2 diabetes with IS, ICH, and coronary heart disease in two-sample Mendelian randomization analyses based on summary statistics from European population genome-wide association studies (P for heterogeneity >0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.

Increased ischemic stroke risk in patients with Behçet's disease: A nationwide population-based cohort study.

BackgroundBehçet’s disease (BD) is a recurrent, multisystemic, inflammatory disorder that mainly affects blood vessels. Because recurrent inflammation of blood vessels in the brain plays a crucial role in the development of ischemic stroke, we hypothesized that patients with BD might have an elevated risk of ischemic stroke. This potential association has been suggested in a few case reports, but not epidemiological studies. Hence, the present study aimed to examine the relation between BD and subsequent ischemic stroke in Taiwan using a nationwide, population-based database.MethodsTo establish a study cohort, the longitudinal data of 306 patients newly diagnosed with BD during 2000–2010 were extracted from the National Health Insurance Research Database, Taiwan. For comparison of ischemic stroke incidence, a control cohort of 1224 subjects without BD was established using a frequency-matched ratio of 1:4 for age, sex, and pre-existing comorbidities.ResultsDuring the 10-year follow-up, 13 (4.2%) patients with BD and 20 (1.6%) control subjects experienced ischemic stroke. Kaplan–Meier analysis revealed the higher prevalence of ischemic stroke in the BD group (log-rank test, p = 0.001). After adjusting for comorbidities and demographic characteristics, Cox regression analysis revealed that patients with BD had a 2.77-fold risk of ischemic stroke (95% confidence interval, 1.38–5.57) compared to control subjects.ConclusionsPatients with BD have an elevated risk of ischemic stroke. Hence, BD may affect the vascular system in the brain, resulting in a stroke event.

Duration of Heightened Ischemic Stroke Risk After Acute Myocardial Infarction.

BackgroundThe duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain.Methods and ResultsWe performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Both acute MI and ischemic stroke were ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM), diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we did not count strokes occurring during an acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio in each 4‐week interval after discharge. Confidence intervals were computed using the nonparametric bootstrap method. Among 1 746 476 eligible beneficiaries, 46 182 were hospitalized for acute MI and 80 466 for ischemic stroke. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (hazard ratio: 2.7; 95% confidence interval, 2.3–3.2), remained elevated during weeks 5 to 8 (hazard ratio: 2.0; 95% confidence interval, 1.6–2.4) and weeks 9 to 12 (hazard ratio: 1.6; 95% confidence interval, 1.3–2.0), and was no longer significantly elevated afterward.ConclusionsAcute MI is associated with an elevated risk of ischemic stroke that appears to extend beyond the 1‐month window that is currently considered the at‐risk period.

The Relationship Between Ambient Air Pollution and Acute Ischemic Stroke: A Time-Stratified Case-Crossover Study in a City-State With Seasonal Exposure to the Southeast Asian Haze Problem

Studies are divided on the short-term association of air pollution with stroke. Singapore is exposed to seasonal transboundary haze. We aim to investigate the association between air pollution and stroke incidence in Singapore. We performed a time-stratified case-crossover analysis on all ischemic stroke cases reported to the Singapore Stroke Registry from 2010 to 2015. Exposure on days was compared with control days on which exposure did not occur. Control days were chosen on thesame day of the week earlier and later in the same month in the same year. We fitted a conditional Poisson regression model to daily stroke incidence that included Pollutant Standards Index and environmental confounders. The index was categorized according to established classification (0 to 50=good, 51 to 100=moderate, and ≥101=unhealthy). We assessed the relationship between stroke incidence and Pollutant Standards Index in the entire cohort and in predetermined subgroups of individual-level characteristics. There were 29,384 ischemic stroke cases. Moderate and unhealthy Pollutant Standards Index levels showed association with stroke occurrence, with incidence risk ratio 1.10 (95% confidence interval 1.06 to 1.13) and 1.14 (95% confidence interval 1.03 to 1.25), respectively. Subgroup analyses showed generally significant association, except in Indians and nonhypertensive patients. The association was significant in subgroups aged 65 years or older, women, Chinese, nonsmokers and those with history of diabetes, hypertension, and hyperlipidemia. Stratified by age and smoking, the risk diminished in smokers of all ages. Risk remained elevated for 5 days after exposure. We found a short-term elevated risk of ischemic stroke after exposure to air pollution. These findings have public health implications for stroke prevention and emergency health services delivery.