Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis.

Rheumatology A department, Paris Descartes University, Cochin Hospital, APHP, Sorbonne Paris Cité, Paris, France.
Annals of the rheumatic diseases (Impact Factor: 8.11). 11/2011; 71(3):394-9. DOI: 10.1136/annrheumdis-2011-200143
Source: PubMed

ABSTRACT To evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).
Circulating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up.
After the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 27.41) and a history of digital ulcers (HR 9.32, 95% CI 1.51 to 59.83) were identified as independent predictors of a new digital ulcer. In an alternative model excluding patients with a history of digital ulcers at baseline, high PlGF serum levels (HR 13.46, 95% CI 1.58 to 114.73) and low EPC counts (HR 7.95, 95% CI 2.09 to 30.09) remained predictive of new digital ulcer occurrence during follow-up.
This study identified high PlGF serum levels and low circulating EPC counts as predictors of new digital ulcers in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve digital ulcer risk stratification and therefore allow earlier therapeutic intervention.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The concept of personalized medicine has led to a paradigm shift in recent years. It integrates multiple clinical and biological levels of investigation aimed at offering the best possible and patient-tailored healthcare. This holds great potential in a rare and heterogeneous disease such as systemic sclerosis (SSc). The development of validated clinical screening algorithms and the identification of predictors for disease outcomes can help in stratifying patients according to their individual risk of progression. The ongoing search for biomarkers and key pathogenic molecules has brought valuable insights into molecular networks operative in SSc. In parallel, genetic and genomic studies have revealed new SSc susceptibility loci and validated gene expression profiles that might identify patients benefiting from specific therapies. In this review, we focus on recent findings relevant for the concept of personalized medicine in patients with SSc.
    Current Rheumatology Reports 06/2014; 16(6):425.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective. Patients with SSc are at high risk for the development of ischaemic digital ulcers (DUs), which occur in 35% to 60% of SSc patients. The aim of this study was to asses in SSc patients a correlation between intrarenal arterial stiffness and DUs and to evaluate the prognostic value of Doppler indices to predict the new DUs occurrence. Methods. Seventy (58 female and 12 male; mean age 49,5±13,8 years) unselected, consecutive patients with SSc were enrolled. In all patient Doppler ultrasound examination was performed. The following Doppler indices of intrarenal stiffness were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), pulsatile index (PI), systolic/diastolic ratio (S/D). Results. 30 of 70 patients (42%) experienced new DUs. RI, S/D and PI are significantly higher in SSc patient with new DUs than in SSc patients without new DUs. The receiver operating characteristic (ROC) curves demonstrated a good accuracy of new DUs prediction for RI (0,94, p<0,0001), S/D (0,92, p<0,0001), PI (0,88, p<0,0001). Conversely, the ROC curve showed no performance for PSV (0,58, p>0,05) and EDV (0,28, p>0,05). Using this cut-off value of 0,70 for RI and 3,25 for S/D the positive predictive value was 90,6% and 92,9%, respectively. Conclusions. We can conclude that Doppler indices of intrarenal stiffness are reliable markers of new DU occurrence. Doppler indices could be used in association to the capillaroscopic and clinical findings or serological tests for the identification of patients at high risk of developing DUs. © 2014 American College of Rheumatology.
    Arthritis care & research. 02/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multisite photoplethysmography (PPG) cardiovascular assessments can evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of this pilot study was to investigate the potential clinical utility of the technology in assessing patients with SSc and primary RP (PRP).
    Rheumatology (Oxford, England) 05/2014; · 4.24 Impact Factor

Full-text (2 Sources)

Available from
Jun 10, 2014