Abstract

IntroductionWhether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA.MethodsWe determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models.ResultsTotal and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ≤0.03). Ethnic origin did not impact on these relationships (interaction P ≥0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ≤0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ≤0.006 for triglyceride concentrations and -0.302 to -0.390, P ≤0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ≤0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized β (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation.ConclusionIn this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation.

Highlights

  • Whether adiponectin levels associate with atherogenesis in rheumatoid arthritis (RA) is uncertain

  • We examined the impact of population grouping on independent total and high molecular weight (HMW) adiponectin concentration-metabolic cardiovascular risk factor relationships and whether adiponectin levels associate with surrogate markers of enhanced early atherogenesis including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) [40,41,42,43,44,45,46,47], in both black and white patients

  • These comprise the activating effects of adiponectin on endothelial nitric oxide (NO) synthase and cyclooxygenase-2 leading to the production of NO and prostaglandin-I2 production, respectively, and the ability of adiponectin to promote macrophage polarization toward the anti-inflammatory phenotype, which results in reduced interleukin-6, tumor necrosis factor (TNF)-α and Monocyte chemoattractant protein (MCP)-1 and increased arginase-1, interleukin-1 and macrophage N-acetyl-galactosamine specific lectin-1 by M1 and M2 macrophages, respectively [66]

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Summary

Introduction

Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. Adiponectin decreases free fatty acid production and enhances insulin sensitivity [3] and its circulating concentrations associate with reduced plasma glucose and serum triglyceride levels and increased high density lipoprotein cholesterol concentrations, decreased blood pressure and a lower risk of type 2 diabetes [2,4,5,6,7,8]. These effects of adiponectin would be expected to translate into reduced cardiovascular disease risk. While among the different isoforms of adiponectin, it is high molecular weight (HMW) adiponectin that confers the potential antidiabetic [18] and vascular protective activities [19] of adiponectin in the general population, a potential association with incident coronary heart disease was not confirmed [20]

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