title: The interface of inflammation and subclinical atherosclerosis in granulomatosis with polyangiitis (Wegener's): a preliminary study.
abstract: The objective of this study is to assess the relationship between inflammatory disease in granulomatosis with polyangiitis (GPA, Wegener's) and the development of subclinical atherosclerosis. A total of 46 adult patients with GPA were enrolled. Disease status was measured by Birmingham vasculitis assessment scores as modified for GPA, vasculitis damage index, disease duration, and number of relapses. Classic atherosclerotic risk factors, platelet aggregation responses, and circulating microparticle (MP) levels were recorded. All patients underwent carotid artery intima-media thickness (IMT) measurement as outcome for subclinical atherosclerosis. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age were significantly associated with higher IMT (ρ values 0.37, 0.38, 0.35, and 0.054, respectively [P < 0.02 for all]). In a multiple regression model, greater number of relapses, older age at the onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT (P values 0.003, <0.001, and 0.031, respectively). MP counts and platelet reactivity correlated well with disease activity in GPA. Furthermore, MPs were found to activate vascular endothelial cells and platelets in vitro. The cumulative burden of systemic inflammation in GPA correlated with the development of subclinical atherosclerosis. The correlation with subclinical atherosclerosis could be because of glucocorticoid use and not the inflammatory process in GPA, giving the inherent bias that exits with the use of glucocorticoid with each relapse. The findings of increased levels of circulating leukocyte-derived MPs and enhanced platelet reactivity during relapse suggest possible roles for MPs and platelets in disease pathogenesis and support a growing literature that links inflammation, atherosclerosis, and platelet activation. This hypothesis is further substantiated by our demonstration that MPs isolated from plasma of GPA patients can activate platelets and vascular endothelial cells.
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio. Electronic address: hajjalr@ccf.org.
authors.forename: Rula A
authors.initials: RA
authors.lastname: Hajj-Ali
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Major
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Carol
authors.initials: C
authors.lastname: Langford
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Garry S
authors.initials: GS
authors.lastname: Hoffman
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Clark
authors.affiliation: Department of Epidemiology and Statistics, University of California, San Francisco, San Francisco, Calif.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Quantitative Health Science, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wis.
authors.forename: Roy L
authors.initials: RL
authors.lastname: Silverstein
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D059168:Carotid Intima-Media Thickness; D055252:Cell-Derived Microparticles / Q000187:drug effects; D015331:Cohort Studies; D003710:Demography; D003971:Diastole / Q000187:drug effects; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D018799:Intercellular Adhesion Molecule-1; D000244:Adenosine Diphosphate