Macrophage-mediated inflammation and microcalcification are associated with abdominal aortic aneurysm progression and clinical events.

Forsythe, Rachael O; McBride, Olivia M B; Robson, Jennifer M J; Vesey, Alex T; Winarski, Allison C; Weston, Callum; Debono, Samuel; Semple, Scott I et al. · Br J Surg · 2026

prospective_cohort · Level II

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Abstract

Molecular and cellular imaging biomarkers of abdominal aortic aneurysms (AAA) show promise as potential predictors of clinical events. This study assessed long-term clinical outcomes using ultrasmall superparamagnetic particles of iron oxide (USPIO) enhanced magnetic resonance imaging (MRI; ISRCTN76413758) and fluorine-18 sodium fluoride ([18F]NaF) positron emission tomography computed tomography (PET/CT; NCT02229006). A prospective multi-centre co-enrolled observational cohort studies of patients with asymptomatic AAA. Evaluation of aortic wall inflammation using USPIO-enhanced MRI in 338 patients was followed by [18F]NaF PET/CT in a sub-group of 72 patients, to evaluate microcalcification. Aneurysms were classified according to aortic wall USPIO enhancement and into tertiles of [18F]NaF uptake. Aneurysm expansion, composite of rupture or repair, and overall survival were compared. In 338 predominantly elderly (74±7.2 years) men (85%) with mean aneurysm diameter 49.5±7.3 mm, aneurysm expansion was increased in patients with USPIO enhancement (median [inter-quartile interval], 3.3 [2.0-4.6] versus 2.5 [1.4-3.6] mm/y; p=.002) or high [18F]NaF uptake (4.0 [2.6-5.4] versus 1.9 [0.9-3.0] mm/y; p<.001), even when adjusted for hypertension, smoking and baseline AAA diameter (p=.04 and p=.003). After a median follow up of 102 [58-119] months, 63% patients met the composite endpoint of rupture or repair with high [18F]NaF uptake associated with more than two-fold higher risk (72% versus 36%; log rank p=.002). There was no association between USPIO enhancement and future rupture or repair. Aortic wall USPIO enhancement and [18F]NaF uptake are independently associated with AAA expansion. These non-invasive imaging biomarkers provide an opportunity to identify those are at greatest risk of AAA progression and may help inform further research to determine optimal surveillance intervals.