Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

Manuela Di Franco,Maria Chiara Gerardi,Cristina Iannuccelli,Francesca Romana Spinelli,Francesco Ciciarello,Luciano Agati,Virginia Conti,Francesca Boccalini,Guido Valesini,Alessio Metere

doi:10.1155/2012/347268

Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

Manuela Di Franco, Maria Chiara Gerardi + Show 8 more

Open Access

https://doi.org/10.1155/2012/347268

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Abstract

Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.

Highlights

Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with increased cardiovascular morbidity and mortality [1,2,3,4,5]
Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA)
The increased risk of cardiovascular disease observed in RA can be attributed to accelerated, early atherosclerosis

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with increased cardiovascular morbidity and mortality [1,2,3,4,5]. Comprehensive care of patients with RA implies prevention and treatment of joint damage and of co-morbidities, cardiovascular disease, which is the cause of 40%–50% of the deaths in this population [4, 5]. Evidence of subclinical CVD has been demonstrated in patients with early RA (ERA) [12]. These patients have been found to have a higher prevalence of atherosclerotic plaques, increased intima-media thickness (IMT) of the carotid arteries [13, 14], and significantly impaired endothelial function compared with controls [15]. The high frequency in RA patients of risk factors like smoking, dyslipidemia, hypertension, diabetes mellitus, and increased body mass index accounts only partially for their high

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