Detection of early endothelial damage in patients with Raynaud's phenomenon

Microvasc Res. 2017 Sep;113:22-28. doi: 10.1016/j.mvr.2017.04.004. Epub 2017 Apr 25.


Objectives: Raynaud's phenomenon (RP) can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an overt disease by years. It is not known if markers of endothelial damage are detectable in those RP patients who subsequently develop a CTD.

Methods: We studied 82 RP patients at their first evaluation to correlate the levels of endothelial markers with the subsequent development of an overt disease 36months later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6 (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects (HS) served as controls.

Results: At baseline, 67 patients showed capillaroscopic normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6 were higher in patients with CNP (p=0.0001) than in HS and even much higher in patients with CSP (p=0.0001). In patients with CNP and RP of recent onset (<18months), vWF plasma levels were higher when autoantibodies were present (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow-up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal levels of t-PA, IL-6 and particularly vWF were higher than in primary RP (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all).

Conclusions: Our findings indicate that markers of endothelial damage are elevated in RP patients who subsequently develop SSc or other CTDs, even in the absence of capillaroscopic abnormalities.

Keywords: Autoantibodies; Capillaroscopy; Endothelial damage; Interleukin-6; Raynaud's phenomenon; Systemic sclerosis; Tissue-type plasminogen activator; Very early systemic sclerosis; von Willebrand factor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Autoantibodies / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Early Diagnosis
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Microscopic Angioscopy
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Raynaud Disease / blood*
  • Raynaud Disease / pathology
  • Time Factors
  • Tissue Plasminogen Activator / blood*
  • Up-Regulation
  • Young Adult
  • von Willebrand Factor / metabolism*


  • Autoantibodies
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • von Willebrand Factor
  • Tissue Plasminogen Activator