Endothelial dysfunction, microvascular damage and ischemic peripheral vasculopathy in systemic sclerosis

Clin Hemorheol Microcirc. 2017;66(2):117-130. doi: 10.3233/CH-150044.


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: ADMA; Allen test; ET-1; Systemic sclerosis; and microangiopathy evolution score; capillaroscopy; digital ulcers; flow-mediated dilatation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Fingers / pathology*
  • Humans
  • Male
  • Microscopic Angioscopy / methods*
  • Middle Aged
  • Peripheral Vascular Diseases / etiology*
  • Peripheral Vascular Diseases / pathology
  • Risk Factors
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / pathology
  • Ulcer / etiology*
  • Young Adult