London, United Kingdom 2013 18 Etiology of stroke and risk factors B 17:50 - 18:00 The association of ischemic stroke etiology and extremes of retinal microvessel complexity D.A. De Silva1, R.S. Shekhawat2, J.C. Allen3, C.P.L.H. Chen4, H.M. Chang5, C. Cheung6, K. Ikram7, T.Y. Wong8, M.C. Wong9 National Neuroscience Institute, Singapore, SINGAPORE1,Singapore General Hospital, Singapore, SINGAPORE2, Duke-National University of Singapore, Singapore, SINGAPORE3, National University of Singapore, Singapore, SINGAPORE4, National Neuroscience Institute, Singapore, SINGAPORE5, Singapore Eye Research Institute, Singapore, SINGAPORE6, Singa-pore Eye Research Institute, Singapore, SINGAPORE7, Singapore Eye Research Institute, Sin-gapore, SINGAPORE8, National University of Singapore, Singapore, SINGAPORE9 Introduction: The etiology of ischemic stroke may involve large and small cerebral vessel dis-ease. Retinal microvessels changes can be examined with from photographs and are postulated to mirror those of the cerebral microvasculature. Retinal microvessel fractal dimension is a marker of geometric complexity. One published study found that small vessel stroke etiology was associated with increased retinal fractal dimension while another found an association with decreased fractal dimension. Deviation from optimal fractal dimension, at both extremes, is postulated to impair the efficiency of microvessel transport. We studied the association of isch-emic stroke etiology and extremes of retinal microvessel fractal dimensions. Methods: This is a prospective study of ethnic Asian ischemic stroke patients, who had retinal photographs taken and analyzed for retinal microvessel fractal dimension in a semi-automated manner, blinded to stroke etiology. Retinal fractal dimension was divided into quartiles with de-viation defined as the lowest and highest quartiles. Results: Among the 806 patients studied, 34% had small vessel etiology and 24% large vessel etiology. A higher proportion of patients with large vessel stroke had deviant retinal fractal di-mension (58%) compared to those with small vessel stroke (45%) (p=0.001). This difference persisted following adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smok-ing and atrial fibrillation (p=0.017). Conclusions: We found an association between large vessel etiology and deviation of retinal microvessel complexity, independent of demographics and traditional risk factors. This may be due to novel risk factors and mechanisms with a predilection for large versus small cerebral vessel disease, which also result in extremes of microvessel complexity. Our finding of an asso-ciation between stroke etiology and deviation of retinal fractal dimension, may explain the con-tradictory findings in previous studies. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 77 17 Etiology of stroke and risk factors B 17:40 - 17:50 Associations between recently discovered genetic variations in metabolic traits and arteri-al stenosis in patients with recent cerebral ischemia E.G. van den Herik1, M.V. Struchalin2, S. Fonville3, L.M.L. de Lau4, H.M. den Hertog5, P.J. Koudstaal6, C.M. van Duijn7 Erasmus MC University Medical Center, Rotterdam, THE NETHERLANDS1,Erasmus MC University Medical Center, Rotterdam, THE NETHERLANDS2, Erasmus MC University Medical Center, Rotterdam, THE NETHERLANDS3, Erasmus MC University Medical Cen-ter, Rotterdam, THE NETHERLANDS4, Erasmus MC University Medical Center, Rotterdam, THE NETHERLANDS5, Erasmus MC University Medical Center, Rotterdam, THE NETHER-LANDS6, Erasmus MC University Medical Center, Rotterdam, THE NETHERLANDS7 Background: Recent large genomewide association studies have found many new genes to be associated with metabolic traits including hypertension, lipid levels and diabetes. A next step after gene discovery is to investigate associations between these genes and clinically relevant endpoints. Therefore, we studied the relation between recently discovered genetic variations in metabolic traits and craniocervical artery stenosis, in patients with transient ischemic attack or ischemic stroke. Methods: We included 700 patients with a recent transient ischemic attack or ischemic stroke. In all patients CT-angiography from the aortic arch to the intracranial ves-sels was performed and scored for degree of stenosis in each artery. Our primary outcome was presence of a stenosis ≥30% in any artery. Genotyping was performed with Metabochip, a tar-geted gene chip for metabolic traits containing ≈200,000 SNPs. Results: Five loci were found to be strongly associated with presence of stenosis (GLIS3, p=1.6x10-6; AGBL2, p=1.2x10-4; SBF2, p=7.9x10-5; SCAMP5, p=8.7x10-5; and MC4R, p=1.7x10-4). After adjusting for multi-ple testing using permutation only the GLIS3 locus remained. For this gene, the risk allele was associated with a 2.2 (95%CI 1.6-3.1)-fold increase of stenosis risk. This gene was previously shown to lead to elevated fasting glucose levels. We found no significant association between loci implicated in hypertension or hypercholesterolemia and presence of stenosis. Conclusions: Our study suggests an association between atherosclerosis and a gene implicated in increased fasting glucose levels, but not with blood pressure- or lipid-related genes, in patients with re-cent cerebral ischemia.
Karger_ESC London_2013
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