Background/Purpose: Vascular dysfunction is pivotal in Systemic Sclerosis (SSc) pathogenesis, leading to somatic vascular signs such as pitting scars, Digital Ulcers (DUs), telangiectasia as well as organ complications underpinned by vascular remodelling, namely: Pulmonary Artery Hypertension (PAH), Scleroderma Renal Crisis (SRC), and SSc myocardial involvement. A Unified Vascular Phenotype (UVP) has been conceptualized for SSc, suggesting a common pathogenetic process across these manifestations[1]. Forced Vital Capacity (FVC) to Diffusing capacity of the Lung for Carbon monoxide (DLCO) ratio is a marker of disproportionately reduced gas exchange and has been shown to predict future diagnosis of PAH[2]. Here we tested the value of UVP in predicting onset of severe vascular disease and overall prognosis in SSc.

Methods: Patients fulfilling the 2013 ACR/EULAR SSc criteria in the EUSTAR database and having at least two follow-ups available were included. UVP score was built by assigning one point each for the presence of telangiectasia, pitting scars, and history of DUs, with the further 0 to 4 points, based on the progressive quintile distribution of FVC/DLCO. UVP score was tested in time-to-event analyses for mortality, and a combined “major vascular endpoint” including new diagnosis of PAH, new cardiac failure (LVEF < 45%) or arrhythmia, new SRC, new finger gangrene. Lastly, UVP score was tested for new DUs occurrence, using a marginal means/rate model, allowing for recurring events analysis at patient level. Cox Proportional Hazard (CPH) regressions, with Breslow method for recurrent DUs, were used. Survival functions were plotted with Kaplan-Meier (KM) curves. Data were analysed using R Core Team. EUSTAR CP number 146.

Results: 5545 patients were eligible on date 31^st November 2023, baseline clinical and demographic features are summarised in Table 1. Multivariate CPH showed that UVP score conferred an increased risk of mortality (HR 1.26, 95% C.I. 1.1-1.5, p=0.001) after adjusting for age, sex, LeRoy subset, ethnicity, raised CRP, ESR, antibody profile, SRC, restrictive lung disease (FVC< 80%), and PAH. Other variables associated with mortality in the multivariate regression were age, sex, restrictive lung disease, and PAH diagnosis. UVP score was also significantly associated with a higher risk of developing the “combined vascular endpoint” (HR 1.14, 95% C.I. 1.05-1.24, p=0.004) after adjusting for variables significant in univariate analysis. Other covariates significantly associated with the endpoint were Leroy subset, male sex, restrictive lung disease, and disease duration. Lastly, adjusting for the same covariates, UVP score was significantly associated with new DUs onset in the recurrent events model (HR 1.52, 95% CI 1.43-1.63, p< 0.0001).

Conclusion: Peripheral vascular manifestations and FVC/DLCO, as a surrogate of microvascular dysfunction, can be combined in a UVP that shows significant prognostic value on severe vascular manifestations and mortality. The UVP may aid both clinical trial enrichment and stratified approaches for clinical management.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-unified-vascular-phenotype-score-identifies-systemic-sclerosis-endotypes-and-predicts-prognostic-outcomes-results-from-the-eustar-database/