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AB0353 Independent Paradoxically Inverse Associations of Retinol Binding Protein 4 with Metabolic Risk and Endothelial Activation in the Absence of A Retinol Binding Protein 4 – Atherosclerosis Relationship in Rheumatoid Arthritis
  1. P.H. Dessein1,
  2. L. Tsang2,
  3. G.R. Norton1,
  4. A.J. Woodiwiss1,
  5. A. Solomon3
  1. 1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of Witwatersrand
  2. 2Rheumatology, Milpark Hospital
  3. 3Rheumatology, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa

Abstract

Background Whereas retinol binding protein 4 (RBP) enhances metabolic risk and atherogenesis in non-rheumatoid arthritis (RA) subjects (1,2), its role in atherogenesis in patients with RA is currently unknown.

Objectives We investigated the independent relationships of RBP4 concentrations with cardiometabolic risk, endothelial activation and carotid atherosclerosis in RA.

Methods We assessed RBP4 concentrations and those of endothelial activation molecules including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 by ELISA, and the common carotid artery intima-media thickness and carotid artery plaque by ultrasound in 217 (112 black and 105 white) patients with RA. Relationships were identified in potential confounder and mediator adjusted mixed regression models.

Results RBP4 concentrations were associated with systolic and mean blood pressure, and those of glucose and E-selectin (partial R=-0.207 (p=0.003), -0.195 (p=0.006), -0.155 (p=0.03) and -0.191 (p=0.007), respectively). The RBP4-blood pressure relationships were reproduced in hypertensives but not in normotensives, the RBP4-glucose association in those with but not without a glucose level of >4.8 mmol/l and the RBP4-E-selectin relation in those with but not without ≥2 major traditional cardiovascular risk factors, a Framingham score or ≥2, increased waist circumference as defined by the National Cholesterol Education Program, an RA duration of >10 years, absent or mild disease activity, an erythrocyte sedimentation rate of >12 mm/hr and black ethnicity. The extent of effect of RBP4 concentrations on those of E-selectin was larger in those with compared to those without ≥2 major cardiovascular risk factors (standardized b (SE) = -0.534 (0.174) versus -0.151 (0.081), p=0.04). RBP4 concentrations were not related to carotid intima-media thickness and plaque.

Conclusions This study shows that RBP4 concentrations are paradoxically associated with decreased metabolic risk and endothelial activation but not atherosclerosis in patients with RA. Results obtained in sensitivity analysis suggest that patients with RA may be able to reduce their RBP4 production in the presence of increased CVD risk and that RBP4 may thereby not increase atherosclerosis in RA.

References

  1. Abel ED et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001;409:729-33.

  2. Graham TE et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subject. N Engl J Med 2006;354:2552-63.

Acknowledgements The study was supported by the South African Medical Research Council and National Research Foundation.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2515

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