Investigators meeting. Thursday 7 June 2012
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1 Investigators meeting Thursday 7 June 2012
2 Future plans Substudies Transient neurological episodes Genetics Biomarkers Retina changes Cognitive follow-up study Thrombolysis ICH
3 Transient focal neurological episodes Dr A Charidimou Questionnaire Are they more common in lobar ICH than deep ICH?
4 Genetics Genetics of Cerebral Haemorrhage on Anticoagulants (GOCHA) lead: Dr J Rosand The GOCHA study is multi-site study funded by the National Institute of Health (NIH) Sample size 600 warfarin-related ICH Our UK target 300 cases of warfarin-related ICH Other genetic analyses in ICH (e.g. collagen genes, APOE) will also be possible at UCL depending on funding
5 Biomarkers Dr A Banerjee, Prof G Lip and collaborators Biomarkers of thrombosis, endothelial function have potential utility in risk prediction in atrial fibrillation and stroke (1). Lp-PLA₂ and CRP are biomarkers of coronary atherosclerotic burden and atherosclerosis, and may be important for risk prediction in stroke patients (2,3). Inflammatory biomarkers (IL-6, CRP, fibrinogen and white cell count) are associated with recurrent cardiovascular events in acute stroke patients (4). VEGF has been associated with cerebral microbleeds (5) 1. Montoro-García S, Marín F, Lip GY. Thrombogenesis in lone atrial fibrillation: a role for soluble P-selectin? Europace. 2011;13: Epps KC, Wilensky RL. Lp-PLA- a novel risk factor for high-risk coronary and carotid artery disease. J Intern Med. 2011;269: Kim SJ, Choe YH, Bang OY; for the CHAOS-BIOMARKER Collaborators. Are Stroke Biomarkers Seeing Brain Vessels in Patients With Ischemic Stroke?: A C-Reactive Protein and Homocysteine Study. Stroke Mar 24. [Epub ahead of print] 4. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C. Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study. Stroke. 2011;42: Dassan P, Brown MM, Gregoire SM, Keir G, Werring DJ. Association of Cerebral Microbleeds in Acute Ischemic Stroke With High Serum Levels of Vascular Endothelial Growth Factor. Arch Neurol May 28:1-4. [Epub ahead of print]
6 Primary Questions (1) Are biomarkers of thrombosis, endothelial function or inflammation associated with ICH, stroke/tia or death in patients with previous history of stroke/tia and non-valvular AF? (2) Are biomarkers of thrombosis, endothelial function or inflammation associated with microbleeds?
7 Secondary Questions (3) Are there ethnic differences in the associations with biomarkers among patients with previous stroke/tia and AF? (4) Are biomarkers of thrombosis, endothelial function and inflammation associated with genetic polymorphisms related to the integrity of brain small vessels or warfarin metabolism? (5) Do biomarkers add any predictive value to existing risk scores for bleeding (HAS-BLED) and stroke(cha 2 DS 2 -VASc, CHADS 2 ) in the setting of AF?
8 Substudy design Inclusion criteria All patients included in the main CROMIS-2(AF) study will be eligible for this substudy. Addition to protocol At baseline, the blood levels of lipoproteinassociated phospholipase A2 (Lp-PLA₂) and C- reactive protein (CRP), IL-6, P-selectin, von Willebrand (VWF) and D-dimer. Bloods (frozen plasma) to be processed in Birmingham
9 Progress To apply for BHF project grant in late July 2012
10 Retinal changes in cerebral haemorrhage ABRÀMOFF et al.: RETINAL IMAGING AND IMAGE ANALYSIS 177 Fig. 5. Automated vessel analysis. From left to right: fundus image; retinal specialist annotation; vesselness map from Staal algorithm [76]; vesselness map from direct pixel classification [73]. Dr Ahmed Toosy, Queen Square (Neurophthalmology) cup and rim; cupping. 3) Segmentation of abnormalities: Pixel feature classification is typically performed using a supervised approach. Could retinal changes (vessel size, branching angles, etc) a) blood vessel related abnormalities hemorrhages; Originally, pixel intensity was used as a single feature. More relate to the underlying vasculopathy microaneurysms; neovascularizations; N=20 nerve fiber ICH, infarcts (cottonwool initially spots). at UCL only b) pigment epithelium related abnormalities drusen; hyper and hypopigmentation. c) choroid related abnormalities nevus and melanoma detection; uveitis related choroidal lesions. to the pixels in an image. Pixel classification uses multiple pixel features: numeric properties of a pixel and its surroundings. recently, -dimensional multifeature vectors are utilized including pixel contrast with the surrounding region, its proximity to an edge, and similarity. Two distinct stages are required for a supervised learning/classification algorithm to function: 1) a training stage, in which the algorithm statistically learns to correctly classify pixels from known classifications, and 2) a testing or classification stage in which the algorithm classifies previously unseen images. For proper assessment of supervised classification method functionality, training data and perfor-
11 Predictors of dementia in AF-related stroke Kwok et al, Neurology 2011 AF-related stroke carries a high risk of future dementia
12 Predictors of dementia in AF-related stroke Mechanisms not known? Due to pre-existing neurodegenerative disease or ongoing embolization We have a unique opportunity to prospectively study this in CROMIS-2 We would like to obtain follow-up cognitive data on as the complete AF cohort if possible Telephone (short) version of MOCA at 1 year from recruitment Please let Clare know if you are interested!
13 Thrombolysis-related ICH 70 year old man Presented with sudden left face and arm weakness Hypertensive, previous AF NIHSS 6 BP 200/100
14 Thrombolysed Deteriorated ~7 hours later Drowsy, worsening weakness
15 MRI done 5 days later Diagnosis??
16 Thrombolysis-related ICH Devastating complication Not well understood Currently excluded from CROMIS-2 We would like to include such patients (prospectively and retrospectively) to allow their characteristics to be better defined Is CAA a common cause? Please let Clare know if you are interested!
17 Ideas for further CROMIS-2 substudies are welcome!
18 Thank you for coming! Next CROMIS-2 Investigators meeting planned for UKSF, December 2012, Harrogate Details to be confirmed
19 Dr David Werring Chief Investigator Tel: Ext Dr Andreas Charidimou Clinical Research Fellow Clare Shakeshaft Study Coordinator Tel:
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