Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Relationship between Disease Status in Wegener's Granulomatosis with the Development of Subclinical Atherosclerosis.
Hajj-Ali5, Rula, Silverstein2, Roy, Joseph1, Douglas, Imrey2, Peter, Hoffman4, Gary S., Zhang2, Li, Langford3, Carol A.
A role for inflammation in the development of accelerated atherosclerosis in patients with chronic inflammatory disease has been proposed. However, the pathophysiology of this process is not fully understood. The objective of this study was to asses the relationship between inflammatory disease in Wegener's granulomatosis (WG) with the development of subclinical atherosclerosis.
Eligible consenting adult patients who met the 1990 ACR classification criteria for WG were enrolled from the Cleveland Clinic Center for Vasculitis Care and Research. Exclusion criteria included history of coronary heart disease, heart failure, stroke, peripheral vascular diseases, acute or chronic infection within the past 3 months, NSAID or aspirin use within a week of MP and platelet studies, or diagnosis of chronic inflammatory disease, an autoimmune disease, or thrombophilia. Disease status was measured by BVAS-WG, VDI, disease duration and numbers of relapses (from onset of disease diagnosis until enrollment in the current study). Classic atherosclerotic risk factors and other co-morbidities were recorded in addition to platelet aggregation responses and circulating microparticle (MP) levels. All patients underwent ultrasound of the carotid arteries to assess intima media thickness (IMT) as an outcome for subclinical atherosclerosis.
45 WG patients were included. In univariate analyses, systolic and diastolic blood pressure, creatinine, and age at onset of disease were significantly associated with a higher IMT with rho values of 0.37, 0.38, 0.35 and 0.54 respectively (p < 0.02 for all), determined by Spearman rank correlation (Table 1).
Table 1. Spearman rank correlation between IMT and patient characteristics
|IMT||Systolic blood pressure||45||0.37||(0.09, 0.66)||0.012|
|IMT||Diastolic blood pressure||45||0.38||(0.09, 0.66)||0.011|
|IMT||Age at onset of disease||45||0.54||(0.28, 0.80)||<0.001|
|IMT||Disease Duration||45||0.23||(-0.07, 0.53)||0.13|
|IMT||Azathioprine Duration||45||-0.24||(-0.53, 0.06)||0.12|
|IMT||Methotrexate Duration||45||0.11||(-0.20, 0.41)||0.48|
|IMT||Cyclophosphamide Duration||45||-0.13||(-0.43, 0.18)||0.41|
|IMT||Cumulative Dose of cyclophosphamide||45||-0.15||(-0.45, 0.16)||0.34|
|IMT||Total MP counts||45||-0.18||(-0.48, 0.12)||0.23|
|IMT||Annexin counts||45||-0.2||(-0.50, 0.10)||0.18|
|IMT||CD_14 MP counts||45||-0.04||(-0.34, 0.27)||0.81|
|IMT||CD_16 MP counts||45||-0.12||(-0.42, 0.19)||0.45|
|IMT||CD_18 MP counts||45||0||(-0.31, 0.31)||0.99|
|IMT||CD_41 MP counts||45||-0.16||(-0.47, 0.14)||0.29|
|IMT||CD_105 MP counts||45||-0.21||(-0.51, 0.09)||0.16|
|IMT||CD_144 MP counts||45||0||(-0.31, 0.31)||0.99|
|IMT||CD_235 MP counts||43||-0.05||(-0.37, 0.26)||0.73|
|IMT||Platelet aggregation||40||0.24||(-0.08, 0.56)||0.14|
When all variables were considered in a multiple regression model that included the total number of disease relapses, and after adjusting for the other significant factors, higher relapse number, older age at onset of disease, and higher diastolic blood pressure were found to be associated with higher IMT as shown in Table 2.
Table 2. Multiple regression model for assessing the association between IMT and sum of Flares
|Outcome||Parameter||Estimate (%95 CI)||P value|
|IMT||Flare sum||0.0119 (0.0001, 0.0236)||0.003|
|Age at onset of disease||0.005 (0.003, 0.008)||<0.001|
|Diastolic blood pressure||0.0033 (0.0003, 0.0064)||0.031|
This is the first study that addresses disease status as it relates to atherosclerosis in WG. Our data suggests that total number of disease relapses, but not disease duration, is a more important risk factor for atherosclerosis and implies that the cumulative inflammatory events contributes to the development of atherosclerosis.
To cite this abstract, please use the following information:
Hajj-Ali, Rula, Silverstein, Roy, Joseph, Douglas, Imrey, Peter, Hoffman, Gary S., Zhang, Li, et al; The Relationship between Disease Status in Wegener's Granulomatosis with the Development of Subclinical Atherosclerosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2049