Background: Patients with small vessel vasculitides (SVV) are at an increased risk of developing macroangiopathy, as well as cardiovascular (CV) and cerebrovascular (CVB) events [1, 2]. However, research on SVV has primarily focused on microangiopathic manifestations, leaving the angiopathy of large vessels and associated CV and CVB risks insufficiently explored [3]. In particular, data on risk stratification strategies for patients with SVV remain limited, and traditional CV scores appear to underestimate risk. Surrogate CV and CVB risk markers have demonstrated improved stratification in the general population and are endorsed by the European Society of Cardiology (ESC) for clinical use. In particular, aortic stiffness and carotid artery sonography are supported by high levels of evidence for their predictive value in assessing CV and CVB risk.

Objectives: Aim of this study was to examine, for the first time, a comprehensive panel of gold standard CV-risk surrogates [4], along with subclinical atherosclerosis indices and novel CVB Doppler-sonographic markers in a large cohort of patients with SVV (VASculitis associated CARDiovascular risk; VASCARD cohort). Additionally, it sought to evaluate correlations of these markers with disease- and patient-associated characteristics, as well as with traditional CV risk factors.

Methods: The VASCARD cohort-study focuses on CV/CVB surrogate marker assessments in SVV patients from two Rheumatology centers. Patients and healthy controls underwent oscillometric and B-mode ultrasound (US) examinations (aortic stiffness, carotid-Intima-Media-Thickness, qualitative & quantitative plaque assessment), as well as novel Doppler-US-assessments [resistance- (RI) & pulsatility- (PI) indices and flow velocity integral (FVI)] of the common (CCA) and internal carotid arteries (ICA). Moreover, disease associated characteristics, clinical and serological activity markers, as well as traditional CV risk factors were documented.

Results: We recruited 122 patients with SVV [granulomatosis with polyangiitis ( n=82 ), microscopic polyangiitis ( n=14 ), eosinophilic granulomatosis with polyangiitis ( n=8 ), cryoglobulinemic vasculitis ( n=2 ), urticaria vasculitis ( n=1 ) and unspecified SVV ( n=17 ): 63,9% female, median age 58 years ( 52 - 66.25 , IQR)] and 150 healthy controls [ 84% female, median age 53 years (43 - 59 , IQR )]. cfPWV was significantly higher in the patient group, compared to the control group, even after statistical corrections for confounding factors [7.78 ( 7.04 - 9.28, IQR ) m/s vs. 7.2 ( 6.2 - 7.95 , IQR) m/s; p _adj <0.001 ]. Moreover, PI and RI of the CCA and ICA respectively were significantly higher in patients compared to controls [CCA-PI: 1.99 (1.61 - 2.29, IQR ) vs. 1.61 (1.39 - 1.84, IQR ), p<0.001 ; CCA-RI: 0.78 ( 0.75 - 0.83, IQR ) vs. 0.74 ( 0.69 - 0.77, IQR ), p<0.001 , ICA-PI: 1.31 ( 1.07 - 1.68 , IQR ) vs. 1.23 ( 0.96 - 1.54 , IQR ), p=0.023 , ICA-RI: 0.69 ( 0.62 - 0.75 , IQR ) vs. 0.66 ( 0.6 – 0.73, IQR ), p=0.036 ). Importantly, cIMT was higher in patients than controls [ 0.89 (0.78 - 1.05 ) mm vs. 0.83 (0.7 – 0.92 ) mm, p<0.001] and associated inversely with pulmonary CO-diffusion. CCA-PI correlated with CRP ( rho=0.378, p<0.001 ) and ESR ( rho=0.239, p=0.04 ) and cfPWV correlated mainly with traditional CV risk factors like age, mean arterial pressure and low density lipoprotein (all; p<0.05 ).

Conclusion: This study is among the most extensive investigations of surrogate markers in SVV. Our findings revealed increased aortic stiffness, carotid resistance, pulsatility, and atherosclerosis in SVV patients compared to controls. Notably, carotid pulsatility was linked to systemic inflammation, and additional key predictors of impaired CV and CVB markers were identified among disease and patient-specific characteristics. Given that these surrogates provide a comprehensive assessment of large artery health, CV and CBV screening can be significantly improved in SVV.

Figure 1.

Differences of surrogate marker values in control subjects and SVV patients (cfPWV, cIMT, ICA-PI, CCA-RI, all; p<0.05* ).SSV: small vessel vasculitides, cfPWV: carotid-femoral pulse wave velocity, cIMT: carotid intima media thickness, ICA-PI: internal carotid artery-pulsatility index, CCA-RI: common carotid artery-resistance index.

REFERENCES: [1] González-Suárez I, et al. Accelerated atherosclerosis in ANCA-associated vasculitis. Acta Neurol Scand. 2017;136(6):688-693.

[2] Chironi G, et al. Increased prevalence of subclinical atherosclerosis in patients with small-vessel vasculitis. Heart. 2007;93(1):96-9.

[3] Triantafyllias K, et al. Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Vasculitides: A Literature Review. Diagnostics (Basel). 2023;13(24):3603.

[4] Triantafyllias K, et al Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A. Rheumatology (Oxford) 2021;60(3):1300-1312.

Acknowledgements: NIL.

Disclosure of Interests: Konstantinos Triantafyllias Chugai, Pfizer, BMS, Novartis, Janssen, UCB, Sanofi, Galapagos, GSK, Boehringer, Novartis, Janssen, Galapagos, Pfizer, Galapagos, Novartis, GSK, Jonas Keil: None declared, Leif-Erik Thiele: None declared, Andreas Schwarting: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.