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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 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. CLINICAL TRIAL REGISTRATION URL:http://www.clinicaltrials.gov. Unique identifier: NCT01063309.

journal_name

Circulation

journal_title

Circulation

authors

Sibley CT,Estwick T,Zavodni A,Huang CY,Kwan AC,Soule BP,Long Priel DA,Remaley AT,Rudman Spergel AK,Turkbey EB,Kuhns DB,Holland SM,Malech HL,Zarember KA,Bluemke DA,Gallin JI

doi

10.1161/CIRCULATIONAHA.113.006824

subject

Has Abstract

pub_date

2014-12-02 00:00:00

pages

2031-9

issue

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.113.006824

journal_volume

130

pub_type

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Assessment of atherosclerosis in chronic granulomatous disease.