Jose Gutierrez1, James Goldman2, Andrew J Dwork2, Mitchell S V Elkind2, Randolph S Marshall2, Susan Morgello2. 1. From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY. jg3233@cumc.columbia.edu. 2. From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
Abstract
BACKGROUND: Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear. METHODS: Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only. RESULTS: Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load. CONCLUSIONS: HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.
BACKGROUND:Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear. METHODS: Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only. RESULTS: Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load. CONCLUSIONS:HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.
Authors: Jose Gutierrez; Melanie Glenn; Richard S Isaacson; Angelica Dawn Marr; Deborah Mash; Carol Petito Journal: Stroke Date: 2011-12-22 Impact factor: 7.914
Authors: Farrah J Mateen; Wendy S Post; Ned Sacktor; Alison G Abraham; James T Becker; Bryan R Smith; Roger Detels; Eileen Martin; John P Phair; Russell T Shinohara Journal: Neurology Date: 2013-11-08 Impact factor: 9.910
Authors: Kunjal Patel; Jiajia Wang; Denise L Jacobson; Steven E Lipshultz; David C Landy; Mitchell E Geffner; Linda A Dimeglio; George R Seage; Paige L Williams; Russell B Van Dyke; George K Siberry; William T Shearer; Luciana Young; Gwendolyn B Scott; James D Wilkinson; Stacy D Fisher; Thomas J Starc; Tracie L Miller Journal: Circulation Date: 2013-12-23 Impact factor: 29.690
Authors: Nina Friis-Møller; Peter Reiss; Caroline A Sabin; Rainer Weber; Antonella d'Arminio Monforte; Wafaa El-Sadr; Rodolphe Thiébaut; Stephane De Wit; Ole Kirk; Eric Fontas; Matthew G Law; Andrew Phillips; Jens D Lundgren Journal: N Engl J Med Date: 2007-04-26 Impact factor: 91.245
Authors: Jose Gutierrez; Tatjana Rundek; Ken Cheung; Ahmet Bagci; Noam Alperin; Ralph L Sacco; Clinton B Wright; Mitchell S V Elkind; Marco R Di Tullio Journal: Cerebrovasc Dis Date: 2017-01-04 Impact factor: 2.762
Authors: Christa Watson; Edgar Busovaca; Jessica M Foley; I Elaine Allen; Christopher G Schwarz; Neda Jahanshad; Talia M Nir; Pardis Esmaeili-Firidouni; Benedetta Milanini; Howard Rosen; Owen T Carmichael; Paul M Thompson; Victor G Valcour Journal: J Neurovirol Date: 2017-01-18 Impact factor: 2.643