Affiliations: [a] Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal
| [b] Department of Health Information and Decision Sciences, Universidade do Porto, CINTESIS - Centre for Research in Health Technologies and Information Systems, Porto, Portugal
| [c] Department of Clinical Pathology, Clinical Chemistry, Centro Hospitalar do Porto, Porto, Portugal
| [d] Clinical Immunology Unit, Centro Hospitalar do Porto (CHP), Instituto de Ciências Biomédicas Abel Salazar, University of Porto (ICBAS/UP), Multidisciplinar Unit of biomedical investigation (UMIB), Porto, Portugal
Correspondence:
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Corresponding author: Ivone Silva, Praça da Revista o Tripeiro, no 42, hab 23, 4150-789 Porto, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal. Tel.: +351 919317751; E-mail: heitor.ivone@gmail.com.
Abstract: OBJECTIVE: To evaluate endothelial dysfunction and microvascular damage in secondary Raynaud Phenomenon (SRP) and Systemic sclerosis (SSc)-associated patients as possible predictors of ischemic fingertip digital ulcers (DU) in a 3-year clinical follow-up. METHODS: Flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) were analysed in a 3-year observational cohort study of 77 SRP patients with systemic sclerosis. The primary outcome was the occurrence of a new DU. RESULTS: Risk factors for DU at baseline were low FMD% (p < 0.001), NVC pattern (p < 0.001), high microangiopathy evolution score (MES) (p < 0.001), increased ET-1 (p < 0.001) and increased ADMA serum levels (p = 0.001). Median time to the occurrence of a new DU was 4.50 (1.25–16.25) months. The risk factors for the occurrence of at least one new DU episode in follow-up included a history of at least one DU before enrolment (p < 0.001), autoantibody anti-scleroderma-70 (p = 0.012), NVC late pattern (p < 0.001), high MES score (p < 0.001), low FMD% (p < 0.001) and increased ET-1 serum levels (p < 0.001). We used univariate Cox regression analysis to show that FMD >9.41% (HR: 0.37 95% CI: 0.14–0.99) and ET-1 >11.85 pmol/L (HR: 3.81 95% CI: 1.41–10.26) and NVC (HR: 2.29 95% CI: 0.97–5.38) were predictors of DU recurrence. In terms of first DU event in naïve DU patients at baseline, late NVC pattern (HR: 12.66 95% CI: 2.06–77.89) and MES score (HR: 1.693 95% CI: 1.257–2.279) were independent predictors. CONCLUSION: This study identified endothelium dysfunction biomarkers (FMD and ET-1) and severe microvascular damage in NVC as strong predictors of new DU in SSc patients.
Keywords: Systemic sclerosis, digital ulcers, flow-mediated dilatation, capillaroscopy, Allen test, ET-1, ADMA, and microangiopathy evolution score
