title: Assessment of atherosclerosis in chronic granulomatous disease.
abstract: BACKGROUND
  Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury.
  
  
  RESULTS
  We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3±76.4 mm(3) versus 463.5±104.7 mm(3); P<0.001). This difference was comparable in p47(phox)- and gp91(phox)-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39).
  
  
  CONCLUSIONS
  The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01063309.
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sibley
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Tyra
authors.initials: T
authors.lastname: Estwick
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Anna
authors.initials: A
authors.lastname: Zavodni
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Kwan
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Soule
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Long Priel
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Rudman Spergel
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Evrim B
authors.initials: EB
authors.lastname: Turkbey
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: Kol A
authors.initials: KA
authors.lastname: Zarember
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: From the Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center (C.T.S., A.Z., A.C.K., E.B.T., D.A.B.), Laboratory of Host Defenses (T.E., P.B.S., A.K.R.S., H.L.M., K.A.Z., J.I.G.), Biostatistics Research Branch (C.-Y.H.), and Laboratory of Clinical Infectious Diseases (S.M.H.), National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute (A.T.R.), National Institutes of Health, Bethesda, MD. jgallin@cc.nih.gov.
authors.forename: John I
authors.initials: JI
authors.lastname: Gallin
mesh_terms: D000328:Adult; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology; D015995:Prevalence; D012307:Risk Factors; D061205:Vascular Calcification / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: atherosclerosis; carotid arteries; coronary vessels; immune system; inflammation