Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Angiogenic Biomarkers Predict the Development of Digital Ulcers in Patients with Systemic Sclerosis.
Avouac1, Jérôme, Meune2, Christophe, Kahan1, Andre, Chiocchia3, Gilles, Allanore1, Yannick
Paris Descartes University, Rheumatology A department, Cochin Hospital, Paris, France
Paris Descartes University, Cardiology department, Cochin Hospital, Paris, France
Institut Cochin, 75014 Paris, France
To evaluate the possible merit of different endothelial markers for the prediction of ischaemic digital ulcers (DU). These biomarkers were also evaluated for the prediction of other microvasuclar complications that are pulmonary hypertension (PH), left ventricular (LV) dysfunction and scleroderma renal crisis (SRC).
Endothelial markers were assessed in a prospective cohort of 100 SSc patients without known cardiovascular involvement or severe comorbidities at presentation. Circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were quantified in peripheral blood by flow cytometry after cell sorting. Serum levels of placenta growth factor (PlGF), soluble vascular adhesion molecule (sVCAM) and vascular endothelial growth factor (VEGF) were measured by quantitative sandwich ELISA technique (Quantikine kits, R&D systems). The primary outcome was the occurrence during a planed 3-year follow-up of one or more new ischemic DU, defined by a painful area >=2mm in diameter with visible depth and loss of dermis localized on fingertips. Secondary endpoint was the occurrence of at least one cardiac/vascular event, assessed by an exploratory composite index defined by the occurrence of at least one of the following event: a) one or more new ischemic DU, b) pre-capillary PH confirmed by RHC, c) left ventricular (LV) dysfunction, defined by a LV ejection fraction (EF)<50% d) SRC, defined by a sudden and marked increase in systemic blood pressure and acute renal failure.
The mean ± standard deviation (SD) age of the 100 patients (89 women) was 56±13 year old and the mean ± SD disease duration was 9±8 years at baseline. Forty patients had the diffuse cutaneous subset, and 60 the limited. During the planned follow-up, seventeen patients developed new ischaemic DU (8 patients with a history of previous DU and 9 patients with no previous DU). Regarding other vascular complications, PH occurred in 5 patients, LV dysfunction in 4 and SRC in a single patient. By univariate analysis, low EPC counts (p=0.009), high PlGF (p=0.007) and sVCAM (p=0.04) serum levels were identified as predictive biomarkers of the occurrence of at least one new DU. Multivariate analysis including these three biomarkers and SSc-related disease characteristics identified high PlGF serum levels (HR: 5.04, 95% CI: 1.1921.09) and a history of DU (HR: 9.51, 95% CI 1.5458.77) as independent predictors of new DU. In an alternate model excluding patients with a history DU at baseline, low EPC counts (HR: 7.95, 95% CI 2.0930.09) and high PlGF serum levels (HR: 13.46, 95% CI 1.58114.73) were found as predictors of new DU. Regarding secondary outcome, Low baseline EPC counts (HR: 4.56, 95% CI 1.0420.06, p=0.03) and elevated PlGF serum levels (HR 5.85 95% CI 1.4224.15, P=0.02) were independent predictors in multivariate analysis of the occurrence of cardiac/vascular events, according to our exploratory index.
This study identified low circulating EPC counts and high PlGF serum levels as predictors of new DU in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve DU risk stratification and therefore allow earlier therapeutic intervention.
To cite this abstract, please use the following information:
Avouac, Jérôme, Meune, Christophe, Kahan, Andre, Chiocchia, Gilles, Allanore, Yannick; Angiogenic Biomarkers Predict the Development of Digital Ulcers in Patients with Systemic Sclerosis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1499