Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes

Stroke ◽  
2021 ◽  
Author(s):  
Jie Xu ◽  
Aichun Cheng ◽  
Bo Song ◽  
Mingming Zhao ◽  
Jing Xue ◽  
...  

Background and Purpose: Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. Methods: A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography–mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. Results: Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15–1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03–2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95–1.48]; cardioembolism, 1.54 [0.95–2.48]; others, 1.19 [0.98–1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91–3.01) and similarly found an increased risk of stroke recurrence. Conclusions: Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

2021 ◽  
pp. svn-2020-000718
Author(s):  
Tingting Wang ◽  
Jie Xu ◽  
Anxin Wang ◽  
Ying Liu ◽  
Xingquan Zhao ◽  
...  

Background and purposeThe association between blood pressure variability (BPV) and stroke recurrence among patients who had ischaemic stroke (IS) remains unclear. This study aimed to investigate the association between BPV and stroke recurrence in patients who had IS of large artery atherosclerosis (LAA) subtype and small artery occlusion (SAO) subtype.MethodsData from the BOSS (Blood Pressure and Clinical Outcome in Transient Ischemic Attack or Ischemic Stroke) study were examined. IS subtypes were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. BPV was performed by 24-hour ambulatory blood pressure monitoring and defined through SD of blood pressure. The primary outcome was stroke recurrence within 90 days after discharge. Multivariable Cox regression model was used to assess the association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype.ResultsA total of 1390 patients who had IS from the BOSS study were included in the present study. Multivariable analysis suggests that 24-hour systolic BPV (SBPV) and night-time diastolic BPV (DBPV) were significantly associated with stroke recurrence among all patients who had IS (HR, 2.50, 95% CI 1.07 to 5.84; HR, 1.85, 95% CI 1.07 to 3.21, respectively). Night-time SBPV and night-time DBPV were significantly associated with stroke recurrence in patients with SAO subtype (HR, 2.77, 95% CI 1.07 to 7.15; HR, 3.60, 95% CI 1.39 to 9.29, respectively). However, in the adjusted model, only night-time DBPV remained significant in patients with SAO subtype (HR, 3.87, 95% CI 1.40 to 10.71). Similar results were not found in patients who had IS of LAA subtype.ConclusionsHigh night-time DBPV was associated with increased risk of stroke recurrence among patients who had IS of SAO subtype. The results of this study have implications for the secondary prevention management and future research of patients who had IS of SAO subtype. The association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype should be investigated in larger, population-based studies.


2019 ◽  
Vol 267 (3) ◽  
pp. 649-658 ◽  
Author(s):  
Petrea Frid ◽  
◽  
Mattias Drake ◽  
A. K. Giese ◽  
J. Wasselius ◽  
...  

Abstract Objective Posterior circulation ischemic stroke (PCiS) constitutes 20–30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. Methods Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. Results PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04–1.61; male sex, OR = 1.46; 95% CI 1.21–1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. Conclusion Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.


Author(s):  
PL Anufriev ◽  
MM Tanashyan ◽  
TS Gulevskaya

The angio- and neurovisualization methods vigorously developing in recent decades determine the relevance of improvement of etiopathogenetic ischemic stroke classification used for the treatment tactics selection and for secondary prevention of the disorder. The study was aimed to clarify the capabilities of clinical diagnosis for pathogenetic variants of ischemic stroke. For that, in 125 postmortem cases, the macro and microscopic examination of brain and cardiovascular system was carried out in order to verify the stroke pathogenesis established as a result of the previous patients’ examination. The study demonstrates the great potential of the major pathogenetic stroke subtypes (large-artery atherosclerosis, cardioembolism, small-artery occlusion) diagnosis using the complex of contemporary clinical and instrumental methods and the main morphological criteria of these subtypes in accordance with the TOAST classification. Moreover, the clinical and pathomorphological assessment allowed us to differentiate stroke resulting from various alterations of single cerebral artery, the atherothrombotic occlusion (44% of cases for the subtype), arterio-arterial embolism (13%) and critical stenosis (10%), as well as stroke resulting from cerebrovascular insufficiency (33%), within the “large-artery atherosclerosis” subtype. Thus, the high informativity of the existing examination methods allows for a more differentiated understanding of the cause of ischemic stroke, which is fully in line with modern personalized medicine.


2018 ◽  
Vol 45 (5-6) ◽  
pp. 279-287 ◽  
Author(s):  
Frans Kauw ◽  
Richard A.P. Takx ◽  
Hugo W.A.M. de Jong ◽  
Birgitta K. Velthuis ◽  
L. Jaap Kappelle ◽  
...  

Background: Predictors of recurrent ischemic stroke are less well known in patients with a recent ischemic stroke than in patients with transient ischemic attack (TIA). We identified clinical and radiological factors for predicting recurrent ischemic stroke in patients with recent ischemic stroke. Methods: A systematic search in PubMed, Embase, Cochrane Library, and CINAHL was performed with the terms “ischemic stroke,” “predictors/determinants,” and “recurrence.” Quality assessment of the articles was performed and the level of evidence was graded for the articles included for the meta-analysis. Pooled risk ratios (RR) and heterogeneity (I2) were calculated using inverse variance random effects models. Results: Ten articles with high-quality results were identified for meta-analysis. Past medical history of stroke or TIA was a predictor of recurrent ischemic stroke (pooled RR 2.5, 95% CI 2.1–3.1). Small vessel strokes were associated with a lower risk of recurrence than large vessel strokes (pooled RR 0.3, 95% CI 0.1–0.7). Patients with stroke of an undetermined cause had a lower risk of recurrence than patients with large artery atherosclerosis (pooled RR 0.5, 95% CI 0.2–1.1). We found no studies using CT or ultrasound for the prediction of recurrent ischemic stroke. The following MRI findings were predictors of recurrent ischemic stroke: multiple lesions (pooled RR 1.7, 95% CI 1.5–2.0), multiple stage lesions (pooled RR 4.1, 95% CI 3.1–5.5), multiple territory lesions (pooled RR 2.9, 95% CI 2.0–4.2), chronic infarcts (pooled RR 1.5, 95% CI 1.2–1.9), and isolated cortical lesions (pooled RR 2.2, 95% CI 1.5–3.2). Conclusions: In patients with a recent ischemic stroke, a history of stroke or TIA and the subtype large artery atherosclerosis are associated with an increased risk of recurrent ischemic stroke. Predictors evaluated with MRI include multiple ischemic changes and isolated cortical lesions. Predictors of recurrent ischemic stroke concerning CT or ultrasound have not been published.


Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2778-2785 ◽  
Author(s):  
Viktoria Rücker ◽  
Peter U. Heuschmann ◽  
Martin O’Flaherty ◽  
Michael Weingärtner ◽  
Manuela Hess ◽  
...  

Background and Purpose: Data on long-term survival and recurrence after stroke are lacking. We investigated time trends in ischemic stroke case-fatality and recurrence rates over 20-years stratified by etiological subtype according to the Trial of ORG 10172 in Acute Stroke Treatment classification within a population-based stroke register in Germany. Methods: Data was collected within the Erlangen Stroke Project, a prospective, population-based stroke register covering a source population of 105 164 inhabitants (2010). Case fatality and recurrence rates for 3 months, 1 year, and 5 years were estimated with Kaplan-Meier estimates. Sex-specific time trends for case-fatality and recurrence rates were estimated with Cox regression. We adjusted for age, sex, and year of event and stratified for etiological subtypes. A sensitivity analysis with competing risk analysis for time trends in recurrence were performed. Results: Between 1996 and 2015, 3346 patients with first ischemic stroke were included; age-standardized incidence per 100 000 was 75.8 in women and 131.6 in men (2015). Overall, 5-year survival probabilities were 50.4% (95% CI, 47.9–53.1) in women and 59.2% (95% CI, 56.4–62.0) in men; 5-year survival was highest in patients with first stroke due to small-artery occlusion (women, 71.8% [95% CI, 67.1–76.9]; men, 75.9% [95% CI, 71.3–80.9]) and lowest in cardioembolic stroke (women, 35.7% [95% CI, 31.0–41.1]; men, 47.8% [95% CI, 42.2–54.3]). Five-year recurrence rates were 20.1% (95% CI, 17.5–22.6) in women and 20.1% (95% CI, 17.5–22.7) in men; 5-year recurrence rate was lowest in women in stroke due to small artery occlusion 16.0% (95% CI, 11.7–20.1) and in men in large-artery atherosclerosis 16.6% (95% CI, 8.7–23.9); highest risk of recurrence was observed in undefined strokes (women, 22.3% [95% CI, 17.8–26.6]; men, 21.4% [95% CI, 16.7–25.9]). Cox regression revealed improvements in case-fatality rates over time with differences in stroke causes. No time trends in recurrence rates were observed. Conclusions: Long-term survival and recurrence varied substantially by first stroke cause. Survival probabilities improved over the past 2 decades; no major trends in stroke recurrence rates were observed.


Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2432-e2443 ◽  
Author(s):  
Joan Martí-Fàbregas ◽  
Santiago Medrano-Martorell ◽  
Elisa Merino ◽  
Luis Prats-Sánchez ◽  
Rebeca Marín ◽  
...  

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.


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