Background/Purpose: The anti-angiogenic isoform of Vascular Endothelial Growth Factor-A (VEGF-A₁₆₅b) has been implicated in Systemic sclerosis (SSc) vasculopathy. High frequency ultrasound (HFUS) is a novel approach to assessing digital perfusion. We report on the relationship between plasma VEGF-A₁₆₅b and peripheral microvascular perfusion using HFUS in SSc.

Methods: Fifty-one patients fulfilling 2013 ACR/EULAR criteria for SSc and fifteen healthy controls (HC) underwent HFUS Doppler assessment of microvascular flow at the distal middle finger, from which a Vascularity Index was calculated. Plasma VEGF-A₁₆₅b levels were assessed using ELISA. Ongoing administration of vasodilator and disease modifying therapies were permitted.

Results: Plasma VEGF-A₁₆₅b was detectable in 16/51 (31%) of SSc with a peak level of >4000pg/mL (Figure 1). In contrast, only 3/15 (20%) healthy controls had plasma VEGF-A₁₆₅b greater than the lower limit of detection by ELISA, with a maximum plasma level of 46pg/mL. Median levels were not significantly different between groups. When VEGF-A₁₆₅b was detectable, it was associated with significantly reduced Vascularity Index in SSc (Figure 2). In contrast, HC showed no difference in the Vascularity Index irrespective of VEGF-A₁₆₅b. Additionally, the Vascularity Index correlated with VEGF-A₁₆₅b in SSc (Spearman’s ρ = -0.289, p=0.039) but not HC. The Vascularity Index was reduced in SSc even in those with undetectable VEGF-A₁₆₅b compared to HC (both with detectable (p=0.047) and undetectable (non-significant) VEGF-A₁₆₅b).

Conclusion: Increased levels of VEGF-A₁₆₅b are associated with reduced digital vascularity in SSc. Low levels of VEGF-A₁₆₅b are sometimes detected in HC but are not associated with reduced digital perfusion. Peripheral vascular compromise in SSc is evident even in the absence of detectable VEGF-A₁₆₅b. Further longitudinal studies are needed to investigate the role of VEGF-A₁₆₅b in determining microvascular flow and the impact of disease duration and intervention on VEGF-A₁₆₅b and digital perfusion over time.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-angiogenic-vegf-a165b-is-associated-with-systemic-sclerosis-peripheral-vasculopathy/