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

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.

Vascular Involvement in Rheumatoid Arthritis

“…The studies revealed a weak correlation between microvascular and macrovascular endothelial dysfunction in RA patients. Microvascular endothelial dysfunction results from the interaction between inflammation, immune dysregulation, and traditional cardiovascular risk factors, representing a significant factor related to accelerated atherosclerosis and future cardiovascular events in RA patients [31].…”

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

“…Rheumatoid arthritis is associated with higher mortality compared to the general population Endothelial dysfunction is common in rheumatoid arthritis and affects both macrovascular and microvascular beds [66,67]. In particular, microvascular endothelial dysfunction affects approximately 33% of patients even in the absence of overt cardiovascular disease [61]. This might account for the reduced coronary flow reserve, and consequent increased risk of ischaemic heart disease, reported in patients with rheumatoid arthritis and other similar autoimmune conditions [68].…”

“…The excess mortality in rheumatoid arthritis is primarily due to cardiovascular death, with a standardized mortality ratio of 1.46 compared to the general population[60]. It is postulated that the state of chronic systemic inflammation in rheumatoid arthritis, and the activation of pro-atherosclerotic cytokines such as TNF-, interleukin 1 (IL-1), and interleukin-6 (IL-6), favours endothelial dysfunction, vascular damage and atherosclerosis(Figure 1)[61][62][63][64]. However, traditional risk factors, such as hypertension, diabetes, obesity, and hypercholesterolaemia, also contribute to the pathogenesis of vascular dysfunction and the risk of adverse cardiovascular outcomes in this group[65].…”

A Novel Use of Structural Equation Modeling to Examine Life-style and Cardio-metabolic Factors Associated With Micro-vascular Endothelial Dysfunction in Middle-aged Chinese Males

“…A weak correlation was found between micro-vascular ED and body mass, and systolic and diastolic blood pressures, triglycerides (TG), high-density lipoproteincholesterol (HDL-c) and glucose in middle-aged men 8 . RHI was associated with blood pressure and HDL-c in chronic kidney disease and rheumatoid arthritis patients 9,10 . However, a negative pro le also existed: RHI measured the micro-vascular ED, but failed to show the correlations with a risk factor pro le (hypercholesterolemia, hypertension, diabetes, and overweight/obesity) in the asymptomatic population [11][12][13] .…”