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SAT0214 Elevated endothelial microparticle levels correlate with endothelial function in active SLE
  1. B. Parker1,
  2. A. Zaki1,
  3. M. Alexander2,
  4. I.N. Bruce1,3
  1. 1Arthritis Research Uk Epidemiology Unit
  2. 2Cardiovascular Research Group, University of Manchester
  3. 3Kellgren Centre for Rheumatology, Manchester Royal Infirmary, Manchester, United Kingdom

Abstract

Background Systemic Lupus Erythematosus (SLE) is associated with an increased risk of clinical and subclinical cardiovascular disease (CVD), including endothelial dysfunction. This elevated CVD risk is multifactorial, but is in part due to exposure to both systemic inflammatory disease activity and corticosteroids. Endothelial microparticles (EMPs) are membrane-bound subcellular particles produced by endothelial cells in response to a variety of activation triggers, including shear stress, inflammatory cytokines and classic CVD risk factors. EMPs are considered to reflect endothelial damage and their levels are elevated in high CVD risk states (such as end-stage renal failure) and may correlate with other measures of endothelial function. Their levels and correlation with endothelial function are unknown in SLE.

Objectives The present study aimed to compare EMP levels in a cohort of patients with active SLE compared to controls. The correlation of EMP levels with endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery was also examined.

Methods Patients with active SLE (≥4 CR criteria) requiring escalation in their anti-inflammatory therapy were recruited. Disease activity (BILAG 2004 and SLEDAI 2K), disease damage (SLICC-DI), current therapies, and clinical features were recorded. Healthy age-matched controls free of CVD risk factors were also assessed. FMD (%) of the brachial artery was measured using 2D ultrasound and automated edge-tracking software, according to international guidelines. EMPs were quantified (number/ml) using flow cytometry after incubating platelet-poor-plasma with the cell surface markers CD31, CD42b and Annexin-V. Events positive for annexin-V and CD31, and negative for CD42b, were classified as EMPs. Continuous data were compared using Mann-Whitney test, and Spearman’s Rank was used to correlate EMP levels with % FMD.

Results 27 patients with SLE (mean (SD) age 41.5 (14.1) yrs) and 22 controls (mean age (SD) 38.5 (9.3) yrs) underwent assessment of endothelial function. The SLE patients had active disease with a mean (SD) SLEDAI-2K of 8.2 (5.5) and 26 BILAG “A” and 16 BILAG “B” scores overall. Endothelial-dependent FMD (%) was significantly reduced in the SLE group compared to controls (median (IQR) FMD1.63% (-1.22, 5.32) vs. 5.40% (3.02, 8.57); p=0.05). Endothelial-independent dilatation of the brachial artery (following administration of sub-lingual GTN 300mcg) was however similar in both groups (median (IQR) GTN-response 15.3% (11.9, 19.06) vs. 12.0% (10.3, 20.5); p = ns), confirming impaired endothelial function. EMPs (n/ml) were significantly elevated in the SLE cohort compared to controls (median (IQR) 157,548/ml (59,906, 272,643) vs. 41,025 (30,179, 98,082); p=0.003). Overall, EMPs demonstrated a significant negative correlation with %FMD (correlation coefficient -0.42; p=0.008).

Conclusions Endothelial function is significantly impaired in young SLE patients compared to healthy controls, reflecting the increased CVD risk observed in the disease. EMPs are significantly elevated in active SLE and their levels correlate with FMD, an established measure of endothelial function. EMPs may therefore act as a biomarker for CVD risk in SLE.

Disclosure of Interest None Declared

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