Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study

Gian Luca Erre, Matteo Piga, Anna Laura Fedele, Silvia Mura, Alessandra Piras, Maria Luisa Cadoni, Ignazio Cangemi, Martina Dessi, Gabriele Di Sante, Barbara Tolusso, Elisa Gremese, Alberto Cauli, Arduino Aleksander Mangoni, Pier Sergio Saba, Ciriaco Carru, Gianfranco Ferraccioli, Alessandro Mathieu, Giuseppe Passiu, Gian Luca Erre, Matteo Piga, Anna Laura Fedele, Silvia Mura, Alessandra Piras, Maria Luisa Cadoni, Ignazio Cangemi, Martina Dessi, Gabriele Di Sante, Barbara Tolusso, Elisa Gremese, Alberto Cauli, Arduino Aleksander Mangoni, Pier Sergio Saba, Ciriaco Carru, Gianfranco Ferraccioli, Alessandro Mathieu, Giuseppe Passiu

Abstract

Objectives: To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events.

Materials and methods: Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis-ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED.

Results: Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218-2.396), p < 0.01 and OR (95% CI) = 1.005 (1.002-1.009), p < 0.01, respectively]. Multiple regression analysis showed a positive correlation between Ln-RHI values and systolic blood pressure and HDL cholesterol levels; furthermore, higher values of Ln-RHI were associated with ACPA positivity, while smoking habit was associated with lower Ln-RHI values.

Conclusions: This study demonstrates for the first time a high prevalence of peripheral microvascular ED in patients with RA free of previous cardiovascular events that appear to be only partially driven by traditional cardiovascular risk factors. The association between ACPA negativity and ED warrants further exploration.

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