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Serum Vascular Cell Adhesion Molecule 1 levels are associated with vascular Dysfunction and increased cardiovascular risk in an animal model and patients with Rheumatoid Arthritis

Davies, Ruth, Iacono, Daniela, Jordan, Lauren, Williams, Jessica O., Sime, Katie, Rawlings, Charlotte, Lang, Derek, Jones, Simon, Williams, Anwen and Choy, Ernest 2016. Serum Vascular Cell Adhesion Molecule 1 levels are associated with vascular Dysfunction and increased cardiovascular risk in an animal model and patients with Rheumatoid Arthritis. Rheumatology 55 (Supp 1) , p. 54. 10.1093/rheumatology/kew102.004

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Background: Mortality is increased in RA patients, mainly due to cardiovascular (CV) disease; however, the biologic mechanisms are unknown. Increased CV risk in RA is attributed to both traditional risk factors and systemic inflammation. CV risk scores, even after modification as recommended by EULAR, underestimate risk in RA and thus there is a need to develop a better means of risk stratification. Murine collagen-induced arthritis (mCIA) is associated with vascular dysfunction, characterized by reduced vascular constriction to 5- hydroxytryptamine (5-HT). This study was undertaken to characterize the relationship between vascular cell adhesion molecule 1 (VCAM-1), which is induced in pro-atherosclerotic conditions in the general population and vascular dysfunction in mCIA and CV risk in RA patients. Methods: mCIA was induced in DBA/1 mice. The severity of arthritis was assessed by the arthritis index score. Constriction responses to 5- HT were used to assess vascular function in isolated sections of thoracic aorta. Serum VCAM-1 was measured with ELISA. Serum VCAM-1, IL-6, ESR and CRP were measured with ELISA in RA patients [182 patients, 4 female:1 male, mean age 60 years (range 21–89), mean disease duration 11.4 years (S.D. 11)]. CV risk was calculated using the Framingham risk calculator and the QRISK2 algorithm. The latter includes RA as an independent CV risk factor. Results: In mCIA, VCAM-1 levels [mean 1500 mg/ml range (929–2528)] correlated with the arthritis index score (r¼0.43, P¼0.03) and negatively correlated with maximal aortic contraction (r¼�0.35, P<0.05). In patients with RA, VCAM-1 was significantly higher in those with a Framingham CV risk score >10% over 10 years [1200 ng/ ml (S.D. 547)] compared with those with <10% risk [937 ng/ml (S.D. 570), P¼0.02]. Similarly, the respective VCAM-1 levels using the QRISK2 were 1179 ng/ml (S.D. 583) vs 949 (S.D. 564), P<0.05]. VCAM-1 was positively correlated with IL-6 levels (r¼0.24, P¼0.008), 28-joint DAS (r¼0.25, P¼0.03) and age (r¼0.26, P¼0.002). There was no statistically significant correlation between VCAM-1 level and disease duration, statin use, BMI, cholesterol, systolic blood pressure, gender or smoking. One of the major differences between QRISK2 and Framingham is inclusion of RA as an independent risk factor in the former. QRISK2 and Framingham CV risk scores were moderately correlated (r¼0.7, P<0.0001). Multivariate analysis using backward stepwise multiple regression found that VCAM-1 (P¼0.002) was a statistically significant independent predictor of QRISK2 score when added to the Framingham score and increased r from 0.6 to 0.62. Conclusion: VCAM-1 levels correlate not only with disease activity and vascular dysfunction in mCIA, but also disease activity and CV risk in RA. VCAM-1 is a potential biomarker for CV disease in RA that warrants further investigation.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Oxford University Press
ISSN: 1462-0324
Last Modified: 24 Feb 2019 00:25

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