Ivone Silva1, Andreia Teixeira2, José Oliveira3, Isabel Almeida4, Rui Almeida5, Carlos Vasconcelos6. 1. Angiology and Vascular Surgery Service and Clinical Immunology Unit, Centro Hospitalar do Porto, Portugal. heitor.ivone@gmail.com. 2. Health Information and Decision Sciences Department, Universidade do Porto; CINTESIS, Center for Research in Health Technologies and Information Systems, Porto, Portugal. 3. Clinical Pathology Department, Clinical Chemistry, Centro Hospitalar do Porto, Portugal. 4. Clinical Immunology Unit, Centro Hospitalar do Porto, Portugal. 5. Angiology and Vascular Surgery Service, Centro Hospitalar do Porto, Portugal. 6. Clinical Immunology Unit, Centro Hospitalar do Porto; Instituto de Ciências Biomédicas Abel Salazar, University of Porto; Multidisciplinar Unit of biomedical investigation, Porto, Portugal.
Abstract
OBJECTIVES: To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. METHODS: Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. RESULTS: After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130). CONCLUSIONS: Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.
OBJECTIVES: To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosispatients. METHODS:Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. RESULTS: After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130). CONCLUSIONS:Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.
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