Background: The mechanisms of vascular degeneration in PSV, although partly described so far, include among others the acceleration of the 3 classical types of arterial damage (inappropriate arterial remodeling, atheromatosis and arteriosclerosis), affecting both the micro- and macro-circulation [1]. This is attributed to the interplay between tissue and systemic inflammation, immunosuppressive therapy, and common cardiovascular disease (CVD) risk factors contributing to the observed increased CVD morbidity and mortality of these patients [2,3]. Based on easy to use, non-invasive vascular indices, the monitoring of subclinical vascular damage not only provides insights on the development of these vascular pathologies in PSV, but might be also used to guide treatment, in similar ways as in individuals with other non-inflammatory as well as systemic autoimmune rheumatic diseases with increased CVD risk including systemic lupus erythematosus and rheumatoid arthritis (RA) [4-6].

Objectives: To explore the presence and potential reversibility of subclinical vascular dysfunction and/or damage both in the micro- and macro-circulation in PSV by evaluating four main vascular pathologies (atheromatosis, arterial stiffening, arterial remodeling and pressure wave reflection impairment) in four different vascular beds (carotid, femoral arteries, aorta, and retina) using gold-standard in clinical practice, non-invasive vascular biomarkers.

Methods: Seventy-three PSV patients [42 (57.5%) with a type of large (LVV), 4 (5.5%) with medium (MVV) and 27 (37%) with small vessel vasculitis (SVV), matched at 1:1 according to age/sex/all CVD risk factors and associated therapies with non-inflammatory controls-(NIC), RA and polymyalgia rheumatica (PMR) controls were studied. Atheromatosis (carotid/femoral plaques), arterial stiffening (carotid-femoral pulse wave velocity-cfPWV), pressure wave reflections (augmentation index-AIx) and arterial remodeling (carotid-intima media thickness-cIMT and retinal vessel calibers) in two time points (activity-remission) were evaluated.

Results: Aortic PWV in PSV was higher by 0.7 m/sec compared to NIC, and by 1.3 m/sec to RA-controls (p=0.003) and was more pronounced in LVV/MVV patients (p=0.08 and p=0.001 respectively). AIx was decreased in all PSV (p=0.03) and predominantly in SVV compared to NIC (p=0.04) and RA-controls (p=0.09 all, p=0.07 active disease). Atherosclerotic plaque formation prevailed in all vascular beds at diagnosis being more enhanced in LVV/MVV (p=0.007, p=0.03, p=0.004), compared to NIC and only both carotid/femoral (p=0.02) to RA-controls. Carotid IMT was higher in LVV/MVV irrespectively to disease state and control group and was the most sensitive to change biomarker between activity-inactivity. Active giant cell arteritis (GCA) was associated with increased PWV/plaques/cIMT compared to matched-NIC, RA and PMR-controls. The retinal microcirculation exhibited vasodilation in at least partly reversible (venules), and irreversible manner [arterioles, NIC (p=0.029) and RA-controls (p=0.008)], associated with the level of the inflammatory response and irrespectively of the underlying disease-specific pathogenetic mechanisms, suggesting that digital retinoscopy might represent an easy direct tool to monitor disease activity in PSV.

Conclusion: Accelerated atheromatosis and arteriosclerosis are present at diagnosis in PSV suggesting disease specific more than drug related pathogenetic links. Early identification and management of CVD risk may reduce long-term CVD morbidity and mortality in PSV patients.

REFERENCES: [1] Argyropoulou OD et al. Curr Opin Rheumatol. 2018.

[2] Savage COS et al. Lancet 1997.

[3] Clifford AH et al. Atherosclerosis. 2021.

[4] Vlachopoulos C et al. Atherosclerosis. 2015.

[5] Drosos GC et al. Ann rheum Dis 2022.

[6] Agca R et al. Ann rheum Dis 2016.

Acknowledgements: Ourania D Argyropoulou and Petros P. Sfikakis (two of the listed authors) are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA-ERN). The study was partially funded by the Hellenic Rheumatology Society.

Disclosure of Interests: None declared.