Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients

Abstract

Objective: The potential contribution of asymmetric dimethylarginine (ADMA) and high-sensitivity C reactive protein (hsCRP) to endothelial dysfunction in APS patients has not been studied in detail, until now. The study involved 105 APS patients (59 diagnosed with primary APS (PAPS) and 46 APS associated with systemic lupus erythematosus (SAPS)) who were compared to 40 controls. Endothelial dysfunction was assessed by measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate dilatation (NMD) of the brachial artery. ADMA (micromol/L) was analyzed by ELISA. Results: FMD in patients with APS was significantly lower than that of the controls (p < 0.001), with no difference between the PAPS and the SAPS groups. ADMA and hsCRP concentrations were significantly higher in the patient cohort than in the control group (p < 0.001, p = 0.006, respectively), as was the case with the SAPS group as compared to the PAPS group (p < 0.001, p = 0.022, respectively). FMD impairment correlated to ADMA (ρ 0.472, p < 0.001) and to hsCRP (ρ 0.181, p = 0.033). In the regression model, the ADMA concentration confirmed the strength of its association (B 0.518, SE 0.183, Wald 8.041, p = 0.005, Exp(B) 1.679, 95% CI 1.174–2.402) to FMD impairment. The synergistic probability model of ADMA and hsCRP caused FMD impairment when the positivity of β2GPIIgG was added. ADMA may be used as a simple and low-cost tool for verifying the presence of endothelial dysfunction in APS patients. According to the results of the study, we could presume that hsCRP, together with aPL, has a preparatory effect on the endothelium in causing endothelial dysfunction.

An update on cardiovascular disorders in systemic lupus erythematosus

“…High serum ADMA levels may represent a risk factor for disease activity and poor prognosis among SLE patients. 135,136 Other potentially useful biomarkers are presented in Table 1. 121,131,[137][138][139] Biomarkers may help to detect SLE patients at high cardiovascular risk and need further investigation to develop personalized treatment.…”

Antiphospholipid Syndrome in Pregnancy: New and Old Pathogenetic Mechanisms

“…The antiphospholipid syndrome (APS) is a systemic autoimmune disorder whose diagnostic criteria were revised in 2006 at the Sydney workshop in Australia. Concisely, APS is characterized by persistent positivity for antiphospholipid antibodies [aPL, including lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein1 antibodies (anti-β 2GPI)], thrombotic events and/or severe pregnancy morbidity [ 1 , 2 , 3 , 4 ]. Beyond the APS-related thrombotic and pregnancy complications, additional clinical conditions, such as cutaneous (livedo reticularis, cutaneous ulcers) haematological (thrombocytopenia, hemolytic anemia), cardiac (cardiac valvular disease), nephrological and neurological manifestations are associated to APS [ 5 ].…”