Abstract
BackgroundSymmetric (SDMA) and asymmetric (ADMA) dimethylarginines have emerged as novel biomarkers of cardiovascular disease (CVD) in several disease settings associated with atherosclerosis. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by high CVD mortality and morbidity. ADMA and SDMA levels are abnormal in RA patients, but their correlation with assessments of endothelial function and structure remains unknown. We aimed to investigate whether SDMA and ADMA are associated with carotid intima media thickness (cIMT) and arterial stiffness as well as non-invasive assessments of in vivo micro- and macrovascular endothelial function in RA patients with high systemic inflammatory load.MethodADMA and SDMA levels were measured using immunoassays in 197 RA individuals. Twenty-six of these [23 (86.4%) females, median age 70, quartiles (60, 73)] were identified as having high inflammatory markers [erythrocyte sedimentation rate (ESR) >25 mm/hr and C-reactive protein (CRP) > 5 mg/L], and were compared to the remainder of the cohort. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function [laser Doppler imaging with iontophoresis of acetylcholine (Ach) and sodium-nitroprusside (SNP) respectively], macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology [pulse wave analysis, and carotid intima media thickness (cIMT)].ResultsSignificant interactions with inflammation were detected in the associations between ACh and both SDMA (p = 0.014) and ADMA:SDMA ratio (p = 0.027), as well as between SNP and SDMA (p = 0.042) and between arterial stiffness and ADMA:SDMA (p = 0.036), with the associations being stronger in the patients with high inflammatory markers in each case.ConclusionsBesides their emerging role as markers of endothelial dysfunction SDMA and ADMA may promote endothelial injury in RA as mediators of the adverse effects of systemic inflammation on micro- and macrovasculature respectively in patients with active disease.
Highlights
Symmetric (SDMA) and asymmetric (ADMA) dimethylarginines have emerged as novel biomarkers of cardiovascular disease (CVD) in several disease settings associated with atherosclerosis
Significant interactions with inflammation were detected in the associations between ACh and both Symmetric dimethylarginine (SDMA) (p = 0.014) and Asymmetic dimethylarginine (ADMA):SDMA ratio (p = 0.027), as well as between SNP and SDMA (p = 0.042) and between arterial stiffness and ADMA:SDMA (p = 0.036), with the associations being stronger in the patients with high inflammatory markers in each case
Significant interactions with inflammation were detected in the associations between vasodilatory responses to acetylocholine (Ach) and both SDMA (p = 0.014) and ADMA:SDMA ratio (p = 0.027), as well as between vasodilatory responses to 1% sodium-nitroprusside (SNP) and SDMA (p = 0.042) and between augmentation index (AIx) and ADMA:SDMA ratio (p = 0.036)
Summary
Symmetric (SDMA) and asymmetric (ADMA) dimethylarginines have emerged as novel biomarkers of cardiovascular disease (CVD) in several disease settings associated with atherosclerosis. Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD), which appears to be of equal frequency and severity to those with diabetes mellitus of similar duration [1]. This elevated CVD risk is only partially explained by the higher prevalence of traditional CVD risk factors in RA [2] and accounts for almost 40–50% of all deaths resulting in premature mortality and reduced life expectancy amongst RA patients compared to the general population [3]. The precise pathogenic mechanisms of CVD remain partially understood It appears that inflammation-induced accelerated atherosclerosis is the main contributor to the excess CVD risk in RA, as inflammatory processes in rheumatoid synovia and atherosclerotic plaque share striking similarities [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
