Faculty Collaboration Database

The interface of inflammation and subclinical atherosclerosis in granulomatosis with polyangiitis (Wegener's): a preliminary study. Transl Res 2015 Oct;166(4):366-74

Date

05/31/2015

Pubmed ID

26024800

Pubmed Central ID

PMC4862201

DOI

10.1016/j.trsl.2015.04.001

Scopus ID

2-s2.0-84941313968 (requires institutional sign-in at Scopus site)   15 Citations

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.

Author List

Hajj-Ali RA, Major J, Langford C, Hoffman GS, Clark T, Zhang L, Sun Z, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Adult
Atherosclerosis
Blood Platelets
Blood Pressure
Carotid Intima-Media Thickness
Cell-Derived Microparticles
Cohort Studies
Demography
Diastole
Female
Granulomatosis with Polyangiitis
Humans
Inflammation
Intercellular Adhesion Molecule-1
Male
Middle Aged
Platelet Aggregation
Recurrence
Regression Analysis
Risk Factors