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Background: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis., Objectives: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment., Methods: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT., Results: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10 -11 . Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10 -10 ; rs1421067 (CHD9), P = 1.81 × 10 -14 ; and rs34780449, near ROBO1 gene, P = 1.64 × 10 -8 . Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10 -14 . Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05)., Conclusion: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the relationship between short-term exposure to outdoor ambient air pollutants (fine particulate matter [PM 2.5 ] and black carbon [BC]), ischemic stroke (IS) and its different subtypes, and the potential modifying effect of neighborhood greenspace and noise., Methods: This time-stratified case-crossover study was based on IS and transient ischemic attacks (TIA) recorded in a hospital-based prospective stroke register (BASICMAR 2005-2014) in Barcelona (Catalonia, Spain). Daily and hourly pollutant concentrations and meteorological data were obtained from monitoring stations in the city. Time-lags (from previous 72h to acute stroke onset) were analyzed. Greenness and noise were determined from the Normalized Difference Vegetation Index (NDVI) and daily average noise level at the street nearest to residential address, respectively., Results: The 2742 cases with known onset date and time, living in the study area, were analyzed. After adjusting for temperature, no statistically significant association between pollutants exposure and overall stroke risk was found. In subtype analysis, an association was detected between BC exposure at 24-47h (odds ratio, 1.251; 95% confidence interval [CI], 1.001-1.552; P = 0.042) and 48-72h (1.211; 95% CI, 0.988-1.484; P = 0.065) time-lag prior to stroke onset and large-artery atherosclerosis subtype. No clear modifying effect of greenness or noise was observed., Conclusions: Overall, no association was found between PM 2.5 and BC exposure and acute IS risk. By stroke subtype, large-artery atherosclerotic stroke could be triggered by daily increases in BC, a diesel fuel-related pollutant in the study area., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Clinical progression in lacunar strokes (LS) is an unpredictable and fearful complication. Endothelial dysfunction (ED) is believed to be the first step in the pathophysiology of LS therefore we aimed to analyze the association of three markers of ED: albuminuria, von Willebrand factor (vWF), and oxidized LDL cholesterol (ox-LDL) with LS progression., Methods: From December 2007 to December 2010, 127 LS patients admitted within 6 h of symptom onset were prospectively assessed. Progression was defined as initial NIHSS score worsening ≥4 points within the first 72 h. Analysis of vWF and ox-LDL was done at admission. Albuminuria was measured in the first morning spot urine. Association between 3 biomarkers and progression was tested using logistic regression analysis. Other clinical variables of interest were also studied. Discriminative power was analyzed with a receiver operator curve., Results: Twenty-two patients (17.3%) progressed. Progression was associated with worse outcome at 90 days. Albuminuria and ox-LDL were associated in univariate analysis; vWF was not. Adjusted OR were: ox-LDL [OR: 1.03; 95% CI: 1.01-1.07, p=0.019], albuminuria [OR: 2.07; 95% CI: 1.04-4.13, p=0.039]. Association was linear without a cut-off point. Clinical variables were not associated with progression. The model including albuminuria and ox-LDL had a good predictive value [AUC: 0.80 [0.70-0.89)]., Conclusions: Albuminuria and ox-LDL levels are independently associated with higher risk of progression in LS. The lack of reliable clinical predictors makes biomarker research a priority to improve progression detection in this subtype of ischemic strokes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)