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SAT0216 Low Reactive Hyperemia Index Assessed By Endo-Pat And High Serum Placenta Growth Factor Associate With Vasculopathy And Disease Progression In Patients With Systemic Sclerosis
  1. S.-Y. Kawashiri1,
  2. Y. Nakashima1,
  3. Y. Horai1,
  4. T. Suzuki1,
  5. A. Okada1,
  6. N. Iwamoto1,
  7. K. Ichinose1,
  8. F. Ogawa2,
  9. S. Ikeda3,
  10. H. Nakamura1,
  11. T. Origuchi4,
  12. K. Aoyagi5,
  13. A. Kawakami1
  1. 1Department Of Immunology And Rheumatology
  2. 2Department of Dermatology
  3. 3Department of Cardiovascular Medicine
  4. 4Department of Health Sciences
  5. 5Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan


Background Vasculopathy and progressive disease status such as digital ulcer, pulmonary arterial hypertension and pulmonary fibrosis deteriorate the quality of life as well as survival rate in patients with systemic sclerosis (SSc). Angiogenesis appears to be dysregulated in patients with SSc and endothelial cell damage may be principal in the disease process of SSc.

Objectives We have explored the surrogate indices to reflect vascular damage and disease progression in patients with SSc using reactive hyperemia index assessed by EndoPAT and serum biomarkers.

Methods Forty-three patients with SSc (limited type; 32 patients, diffuse type; 11 patients) were enrolled. All the patients gave their informed consent to be subjected to the protocol that was approved by the Institutional Review Board of Nagasaki University. They were examined by Chest X-ray or CT, echocardiography, respiratory function test, blood test including autoantibodies and NT-proBNP, endothelial function test by EndoPAT (RHI; Reactive Hyperemia Index), skin assessment by modified Rodonan Skin Score (mRSS) at the same day. Serum concentrations of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) were measured by ELISA. Statistical significance was examined by the Mann-Whitney U test or Spearman’s rank correlation.

Results The mean of age was 63.2 y.o. and that of disease duration was 5.3 years. Eighteen patients complicated with interstitial pneumonia, 3 patients with pulmonary hypertension including border line, and 8 patients with digital ulcer. Anti-Tpo-1 antibodies were positive in 9 patients, anti-centromere antibodies in 25 patients, anti-U1-RNP antibodies in 3 patients, and anti-RNA polymerase III antibodies in 1 patient, respectively. The mean of mRSS was 6.2 points. The mean of RHI was 1.6, which was low as compared with healthy controls, and it was very low in a subset of SSc patients complicated with digital ulcer. The RHI inversely correlated with mRSS (r= -0.4, p < 0.01). The serum levels of PlGF and VEGF were significantly higher as compared with healthy controls (p < 0.01) and the former were higher in diffuse type patients than in limited type patients (p < 0.01). RHI was significantly lower (p < 0.01) and the serum levels of PlGF, but not VEGF, were significantly higher (p < 0.01) in SSc patients complicated with interstitial pneumonia than in the other patients.

Conclusions Low RHI and high serum PIGF may reflect the presence of vasculopathy as well as progressive disease status in patients with SSc. PIGF expression in SSc patients could be augmented by hypoxic environment formed at skin and pulmonary tissues.

References Kawashiri SY, et al. Improvement of plasma endotheline-1 and nitric oxide in patients with systemic sclerosis by bosentan therapy. Submitted.

Acknowledgements n.p.

Disclosure of Interest None Declared

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