Microcirculatory responses at rest and during exercise in limited cutaneous systemic sclerosis compared to age-matched healthy adults

Objectives

Raynaud's phenomenon (RP) is an early manifestation of systemic sclerosis (SSc), reflecting underlying microvascular dysfunction. While exercise improves vascular function, the magnitude and nature of microvascular impairment relative to healthy physiology remain poorly characterised. This study compared resting digital endothelial-dependent and endothelial-independent microvascular responses, together with systemic microcirculatory responses to exercise, between people with limited cutaneous SSc (lcSSc) and age- and gender-matched healthy adults.

Methods

In this cross-sectional case-control study, thirty-four people with lcSSc (65 ± 12 years; 3 males) and 34 healthy adults (64 ± 11 years; 6 males) were assessed. Microvascular function was evaluated using laser Doppler flowmetry (LDF) with iontophoresis of acetylcholine (ACh; endothelial-dependent) and sodium nitroprusside (SNP; endothelial-independent). Systemic physiological responses to exercise were assessed using transcutaneous oxygen pressure (TcpO₂) was measured from the scapular region during moderate-intensity constant-load exercise. Cutaneous vascular conductance (CVC), maximum response (CVCmax), and time to peak response (Tmax) were analysed.

Results

Significant baseline differences were observed for ACh [0.18 (0.09) vs 0.26 (0.09) lcSSc vs HA; p < 0.0001] and SNP [0.19 (0.09) vs 0.27 (0.07); p < 0.0001]. Similar findings were observed for CVCmax [e.g., 1.39 (0.83) vs 3.52 (1.26); p < 0.0001 for ACh] and TcpO₂. No differences were observed for Tmax.

Conclusions

People with lcSSc exhibit marked impairment in resting digital microvascular function affecting both endothelial-dependent and endothelial-independent pathways, alongside a reduced systemic physiological response to exercise, assessed using scapular TcpO₂. These findings highlight diminished microvascular reserve and provide a basis for developing targeted, individualised dose-dependent exercise interventions.

Trial registration

ClinicalTrials.gov (NCT number): NCT03058887. https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1