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  • 1
    In: GeroScience, Springer Science and Business Media LLC, Vol. 42, No. 1 ( 2020-02), p. 57-80
    Type of Medium: Online Resource
    ISSN: 2509-2715 , 2509-2723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2886418-9
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  • 2
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 10 ( 2021-05-18)
    Abstract: Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high‐sensitivity cardiac troponin T (hs‐cTnT) are associated with recurrent vascular events and death in patients with first‐ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS‐B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs‐cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all‐cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs‐cTnT above upper reference limit, 39.2%). During a mean follow‐up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all‐cause death. The primary outcome occurred more often in patients with hs‐cTnT above the upper reference limit (27.3% versus 10.2%; adjusted haza rd ratio, 2.0; 95% CI, 1.3–3.3), with a dose‐response relationship when the highest and lowest hs‐cTnT quartiles were compared (15.2 versus 1.8 events per 100 person‐years; adjusted hazard ratio, 4.8; 95% CI, 1.9–11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs‐cTnT is dose‐dependently associated with an increased risk of recurrent vascular events and death within 3 years after first‐ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs‐cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals. Methods: We conducted a cross-sectional study in the All of Us Research Program, a population study focused on health disparities enrolling 1 million Americans. We used baseline questionnaires to identify participants from sexual minorities (non-straight e.g., gay, lesbian, bisexual) and gender minorities (gender identity different from sex assigned at birth). We further divided gender minorities into gender diverse (e.g., non-binary) and transgender. The primary outcome was a composite of stroke, dementia, and late-life depression. In secondary analyses, we analyzed SGM subgroups and diseases separately. We used multivariate logistic regression to assess the link between SGM groups and brain health outcomes. Results: We included 393,041 participants (mean age 51, female sex at birth 62%), of whom 39,632 (10%) belonged to SGM groups. Of these, 4,431 (1%) belonged to a gender minority (2,212 [50%] gender diverse and 2,219 [50%] transgender) and 38,528 (10%) to a sexual minority. Full results are shown in the Figure. Compared to non-SGM, SGM individuals had 19% higher odds of the brain health composite outcome (OR 1.19, 95%CI 1.13-1.25). These results were consistent across all SGM subgroups (p 〈 0.05). When assessing individual diseases, all SGM groups had higher odds of late-life depression, all SGM except transgender persons had higher odds of dementia, and gender minority groups had higher odds of stroke. Conclusion: In a large US population study, SGM individuals had a higher rate of adverse brain health outcomes. Further research should explore the structural causes of inequity to advance inclusive and diverse neurological care.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Adherence to the American Heart Association's Life’s Essential 8 (LE8) reduces the risk of cardiovascular disease. While the epsilon (ε) 4 variants within the APOE gene have been extensively investigated as a risk factor for dementia and stroke, APOE ε4 carriers have not been thoroughly studied as an at-risk population. We hypothesized that, compared to non-carriers, APOE ε4 carriers derive additional neuro- and cardiovascular health benefits from LE8 optimization. Methods: We used longitudinal data from the UK Biobank (UKB), a large, prospective study undertaken in the UK. Participants with prior stroke, transient ischemic attack (TIA) or myocardial infarction (MI) were excluded. The independent variable or “exposure” was the LE8 score, which was based on data on blood pressure, blood glucose and cholesterol, body mass index, smoking, physical activity, sleep duration and diet. Our outcome was a composite of stroke, TIA or MI. Multivariable logistic regression models with product terms were used to test for interaction between APOE ε4 status and LE8 score. Results: Of the 317,174 UKB participants (mean age 56 years, 54% female) with available genetic and LE8 data, 81,877 (26%) were APOE ε4 carriers (1 or 2 alleles), including 74,384 (91%) heterozygous and 7,493 (9%) homozygous. Among all participants, a 1 SD increase in the LE8 score correlated with a 28% risk reduction for incident stroke, TIA, or MI (OR 0.72, 95%CI 0.71-0.73; p 〈 0.001). APOE ε4 status significantly modified the association between the LE8 score and the composite risk of stroke, TIA, or MI (interaction p=0.008): while APOE ε4 carriers had a 30% risk reduction (OR 0.70, 95%CI 0.68-0.72; p 〈 0.001) per 1 SD increase in the LE8 score, APOE ε4 non-carriers had a 27% risk reduction (OR 0.73, 95%CI 0.72-0.74; p 〈 0.001). Thus, APOE-e4 carriers experienced an 11% increase in benefit. Conclusion: Compared to non-carriers, middle-aged APOE ε4 carriers without a history of vascular events derive greater benefit from LE8 optimization. Now that direct-to-consumer genotyping companies are routinely returning APOE data to millions of Americans, our findings provide important information to educate this population on proven strategies that improve long-term neuro- and cardiovascular outcomes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 10 ( 2022-10), p. 5521-5530
    Abstract: We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term following ischemic stroke. Methods Data were used from the PROSpective Cohort with Incident Stroke-Berlin. NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within 7 days after the first-ever stroke. Seropositivity was defined as titers ≥ 1:10, low titers as ≤ 1:100 and high titers as  〉  1:100. We assessed CF at 1, 2 and 3 years after stroke with the Telephone Interview for Cognitive Status-modified (TICS-m) and used crude and propensity score adjusted inverse probability weighted generalized linear models to estimate the impact of NMDAR1-abs serostatus on TICS-m. Results Data on NMDAR1-abs (median day of sampling = 4[IQR = 2–5]) were available in 583/621 PROSCIS-B patients (39% female; median NIHSS = 2[IQR = 1–4]; median MMSE = 28[IQR:26–30] ), of whom 76(13%) were seropositive (IgM:  n  = 48/IgA:  n  = 43/IgG: n = 2). Any NMDAR1-abs seropositivity had no impact on TICS-m compared to seronegative patients (βcrude = 0.69[95%CI = – 0.84 to 2.23]; βadjusted = 0.65[95%CI = – 1.00 to 2.30] ). Patients with low titers scored better on TICS-m compared to seronegative patients (βcrude = 2.33[95%CI = 0.76 to 3.91]; βadjusted = 2.47[95%CI = 0.75 to 4.19] ); in contrast, patients with high titers scored lower on TICS-m (βcrude =  –2.82[95%CI = – 4.90 to – 0.74], βadjusted = – 2.96[95%CI = – 5.13 to – 0.80] ), compared to seronegative patients. Conclusion In our study, NMDAR1-abs seropositivity did not affect CF over 3 years after a first mild to moderate ischemic stroke. CF differed according to NMDAR1-abs serum titer, with patients with high NMDAR1-abs titers having a less favorable cognitive outcome compared to seronegative patients.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1421299-7
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  • 6
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6582 ( 2022-02-18), p. 782-787
    Abstract: Genetic, functional, and structural features differentiate lineage-specific and cross-reactive anti–SARS-CoV-2 antibodies.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 7
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 6 ( 2021-02-9), p. e937-e946
    Abstract: To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up. Methods In the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured with flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. Results Five hundred seventy-one patients were recruited (median age 69 years, 39% female, median NIH Stroke Scale score 2, interquartile range 1–4), and 95 endpoints occurred. Patients with levels of EMV (adjusted hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2–4.9) or LMV (HR 3.1, 95% CI 1.4–6.8) in the highest quartile were more likely to experience an event than participants with lower levels with the lowest quartile used as the reference category. The association was less pronounced for PMV (HR 1.7, 95% CI 0.9–3.2) and absent for MMV (HR 1.1, 95% CI 0.6–1.8). Conclusion High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients. ClinicalTrials.gov Identifier NCT01363856. Classification of Evidence This study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Neurology Vol. 12 ( 2021-11-8)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 12 ( 2021-11-8)
    Abstract: Objective: Extracellular vesicles (EV) are sub-1 μm bilayer lipid coated particles and have been shown play a role in long-term cardiovascular outcome after ischemic stroke. However, the dynamic change of EV after stroke and their implications for functional outcome have not yet been elucidated. Methods: Serial blood samples from 110 subacute ischemic stroke patients enrolled in the prospective BAPTISe study were analyzed. All patients participated in the PHYS-STROKE trial and received 4-week aerobic training or relaxation sessions. Levels of endothelial-derived (EnV: Annexin V+, CD45–, CD41–, CD31+/CD144+/CD146+), leukocyte-derived (LV: Annexin V+, CD45+, CD41–), monocytic-derived (MoV: Annexin V+, CD41–, CD14+), neuronal-derived (NV: Annexin V+, CD41–, CD45–, CD31–, CD144–, CD146–, CD56+/CD171+/CD271+), and platelet-derived (PV: Annexin V+, CD41+) EV were assessed via fluorescence-activated cell sorting before and after the trial intervention. The levels of EV at baseline were dichotomized at the 75th percentile, with the EV levels at baseline above the 75th percentile classified as “high” otherwise as “low.” The dynamic of EV was classified based on the difference between baseline and post intervention, defining increases above the 75th percentile as “high increase” otherwise as “low increase.” Associations of baseline levels and change in EV concentrations with Barthel Index (BI) and cardiovascular events in the first 6 months post-stroke were analyzed using mixed model regression analyses and cox regression. Results: Both before and after intervention PV formed the largest population of vesicles followed by NV and EnV. In mixed-model regression analyses, low NV [−8.57 (95% CI −15.53 to −1.57)] and low PV [−6.97 (95% CI −13.92 to −0.01)] at baseline were associated with lower BI in the first 6 months post-stroke. Patients with low increase in NV [8.69 (95% CI 2.08–15.34)] and LV [6.82 (95% CI 0.25–13.4)] were associated with reduced BI in the first 6 months post-stroke. Neither baseline vesicles nor their dynamic were associated with recurrent cardiovascular events. Conclusion: This is the first report analyzing the concentration and the dynamic of EV regarding associations with functional outcome in patients with subacute stroke. Lower levels of PV and NV at baseline were associated with a worse functional outcome in the first 6 months post-stroke. Furthermore, an increase in NV and LV over time was associated with worse BI in the first 6 months post-stroke. Further investigation of the relationship between EV and their dynamic with functional outcome post-stroke are warranted. Clinical Trial Registration: clinicaltrials.gov/ , identifier: NCT01954797.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-9-28)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-9-28)
    Abstract: Low ankle-brachial index (ABI) ≤0. 9 is a marker for generalized atherosclerosis and a risk factor for cognitive decline in the general population. Objective To evaluate the impact of ABI ≤0.9 on cognitive function up to 3 years after first-ever ischemic stroke. Methods Data was used from the “PROspective Cohort with Incident Stroke-Berlin” (PROSCIS-B; NCT01363856). ABI was measured at baseline and categorized into normal (1.4–0.9) vs. low (≤0.9). Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental-State-Examination (MMSE) at baseline and with the Telephone Interview for Cognitive Status-modified (TICS-m) at 1–3 years of follow-up. We performed confounder adjusted generalized linear models (GLM) to calculate relative risks (RR) for cognitive impairment at baseline (MMSE≤26; MoCA≤25) and linear mixed models (LMM) to estimate the impact of low ABI on TICS-m over time. Results We included 325 patients [mean age: 66 (SD = 13); 38% female, median NIHSS = 2 (IQR = 1–4), ABI≤0.9: 59 (18%)]. Patients with low ABI were at increased risk of cognitive impairment at baseline (adjusted RR for MoCA≤25 = 1.98; 95%-CI:1.24 to 3.16). TICS-m scores were consistently lower over time in patients with low ABI (adjusted ß = −1.96; 95%-CI:−3.55 to −0.37). Independent of ABI, cognitive function did not decline over time (adjusted ß:0.29; 95%-CI:−0.06 to 0.64). Conclusion In patients with mild to moderate first-ever ischemic stroke, low ABI is associated with reduced cognitive function over a 3-year follow-up. Study Registration https://clinicaltrials.gov ; Unique identifier: NCT01363856.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Poor oral health is a highly prevalent and modifiable risk factor that is associated with higher risk of cardiovascular disease, including ischemic stroke. However, the relationship between oral health and spontaneous intracerebral hemorrhage (ICH) has not been studied. We tested the hypothesis that genetically-determined poor oral health increases the risk of ICH. Methods: We conducted a two-sample Mendelian Randomization (MR) study using summary statistics from the largest genome-wide associations studies of oral health and ICH conducted to date. As genetic instruments (e.g., genetic risk variants for oral health), we identified 105 independent single nucleotide polymorphisms known to be associated with higher risk of caries, dentures and missing teeth at genome wide levels (p 〈 5x10 -8 ). The primary analysis employed summary statistics-based MR to assess the relationship between poor oral health and risk of ICH in any brain location. Secondary analyses evaluated deep and lobar ICH separately. Results: The primary analysis using the inverse variance-weighted MR method showed that genetically-increased risk of poor oral health was associated with a higher risk of ICH (OR 2.34, [1.08-5.06], p=0.029). Secondary analyses indicated a more potent association with deep ICH (OR 3.20 [1.34-7.6] , p=0.008), whereas the link with lobar ICH was not statistically significant (OR 1.32 [0.53-3.27], p=0.543). Sensitivity analyses detected no horizontal pleiotropy in our findings (MR-PRESSO global test p-values 〉 0.05). Conclusion: Genetically-determined poor oral health is associated with an increased risk of ICH, particularly in the case of deep ICH. Because gene-disease associations are less prone to confounding, our results suggest that this association is causal. However, further analyses are needed to validate these results and identify the mediating mechanisms. Because oral health is an easily modifiable process, it may be a promising target for very early interventions focused on mitigating the risk of hemorrhagic stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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