Assessment of atherosclerosis in chronic granulomatous disease

Christopher T. Sibley; Tyra Estwick; Anna Zavodni; Chiung Yu Huang; Alan C. Kwan; Benjamin P. Soule; Debra A.Long Priel; Alan T. Remaley; Amanda K.Rudman Spergel; Evrim B. Turkbey; Douglas B. Kuhns; Steven M. Holland; Harry L. Malech; Kol A. Zarember; David A. Bluemke; John I. Gallin

doi:10.1161/CIRCULATIONAHA.113.006824

Assessment of atherosclerosis in chronic granulomatous disease

Christopher T. Sibley, Tyra Estwick, Anna Zavodni, Chiung Yu Huang, Alan C. Kwan, Benjamin P. Soule, Debra A.Long Priel, Alan T. Remaley, Amanda K.Rudman Spergel, Evrim B. Turkbey, Douglas B. Kuhns, Steven M. Holland, Harry L. Malech, Kol A. Zarember, David A. Bluemke, John I. Gallin

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Methods and 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 mm3 versus 463.5±104.7 mm3; P<0.001). This difference was comparable in p47phox- and gp91phox-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.

Original language	English (US)
Pages (from-to)	2031-2039
Number of pages	9
Journal	Circulation
Volume	130
Issue number	23
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.113.006824
State	Published - Dec 2 2014
Externally published	Yes

Keywords

Atherosclerosis
Carotid arteries
Coronary vessels
Immune system
Inflammation

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1161/CIRCULATIONAHA.113.006824

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Sibley, C. T., Estwick, T., Zavodni, A., Huang, C. Y., Kwan, A. C., Soule, B. P., Priel, D. A. L., Remaley, A. T., Spergel, A. K. R., Turkbey, E. B., Kuhns, D. B., Holland, S. M., Malech, H. L., Zarember, K. A., Bluemke, D. A., & Gallin, J. I. (2014). Assessment of atherosclerosis in chronic granulomatous disease. Circulation, 130(23), 2031-2039. https://doi.org/10.1161/CIRCULATIONAHA.113.006824

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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.Methods and 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 mm3 versus 463.5±104.7 mm3; P<0.001). This difference was comparable in p47phox- and gp91phox-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.",

keywords = "Atherosclerosis, Carotid arteries, Coronary vessels, Immune system, Inflammation",

author = "Sibley, {Christopher T.} and Tyra Estwick and Anna Zavodni and Huang, {Chiung Yu} and Kwan, {Alan C.} and Soule, {Benjamin P.} and Priel, {Debra A.Long} and Remaley, {Alan T.} and Spergel, {Amanda K.Rudman} and Turkbey, {Evrim B.} and Kuhns, {Douglas B.} and Holland, {Steven M.} and Malech, {Harry L.} and Zarember, {Kol A.} and Bluemke, {David A.} and Gallin, {John I.}",

note = "Publisher Copyright: {\textcopyright} 2014 American Heart Association, Inc.",

year = "2014",

month = dec,

day = "2",

doi = "10.1161/CIRCULATIONAHA.113.006824",

language = "English (US)",

volume = "130",

pages = "2031--2039",

journal = "Circulation",

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publisher = "Lippincott Williams and Wilkins",

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T1 - Assessment of atherosclerosis in chronic granulomatous disease

AU - Sibley, Christopher T.

AU - Estwick, Tyra

AU - Zavodni, Anna

AU - Huang, Chiung Yu

AU - Kwan, Alan C.

AU - Soule, Benjamin P.

AU - Priel, Debra A.Long

AU - Remaley, Alan T.

AU - Spergel, Amanda K.Rudman

AU - Turkbey, Evrim B.

AU - Kuhns, Douglas B.

AU - Holland, Steven M.

AU - Malech, Harry L.

AU - Zarember, Kol A.

AU - Bluemke, David A.

AU - Gallin, John I.

PY - 2014/12/2

Y1 - 2014/12/2

N2 - 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.Methods and 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 mm3 versus 463.5±104.7 mm3; P<0.001). This difference was comparable in p47phox- and gp91phox-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.

AB - 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.Methods and 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 mm3 versus 463.5±104.7 mm3; P<0.001). This difference was comparable in p47phox- and gp91phox-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.

KW - Atherosclerosis

KW - Carotid arteries

KW - Coronary vessels

KW - Immune system

KW - Inflammation

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DO - 10.1161/CIRCULATIONAHA.113.006824

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AN - SCOPUS:84916885893

SN - 0009-7322

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SP - 2031

EP - 2039

JO - Circulation

JF - Circulation

IS - 23

ER -

Assessment of atherosclerosis in chronic granulomatous disease

Abstract

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