Peripheral vasculopathy in Raynaud phenomenon: Vascular disease biomarkers

Abstract

Background

Introduction: Raynaud's phenomenon (RP) is a well-defined clinical syndrome. Systemic sclerosis (SSc) is the most frequent associated disease to RP (96%). The aim of this study was to assess the differences between primary RP (PRP) and secondary RP (SRP) regarding macrovascular disease parameters, endothelial dysfunction and angiogenesis biomarkers.

Materials and methods

Flow-mediated dilatation (FMD), endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA) vascular endothelial growth factor (VEGF), endoglin and endostatin were analyzed in a cohort study of 32 PRP patients and 77 SRP all with SSc. 38 of the SRP SSc-associated patients had severe digital ulcer (DU).

Results

Patients with PRP had significantly longer history of RP compared to SRP SSc-sssociated patients (p = 0.028).

FMD was significantly lower in SRP patients 10.85 ± 11.0% (p < 0.001), more evidenced in SRP SSc-associated DU patients 5.34 ± 7.49 (p < 0.001). ET-1 plasma levels were significantly increased in both PRP 7.53 (0.16–11.73) and SRP patients 11.85 (7.42–17.23) (p < 0.001). Significant increased serum levels of ADMA 0.52 (0.45–0.63) μmol/L (p < 0.001) and endoglin 3.01 (1.46–7.02) mg/ml (p < 0.001) were found in the SRP SSc-associated group with DU. VEGF was significantly decreased in the DU group 245.06 (158.68–347.33) pg/ml compared to PRP 438.50 (269.26-854.00) pg/ml and SRP naïve–DU patients 290 (166.71–361.78) pg/ml patients (p < 0.001). No significant differences were found between groups regarding endostatin (p = 0.118).

Comparing PRP and SRP SSc-associated patients without DU no statistically significant difference regarding FMD, ET-1, ADMA, VEGF, plasma levels were observed.

Conclusion

Overproduction of ET-1 and VEGF is present in PRP patients. Macrovascular disease and an impaired response to shear stress are more characteristic of SRP with a grater expression in patients with peripheral ischemic lesions.