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

Abstract

Background: Molecular and cellular imaging biomarkers of abdominal aortic aneurysms (AAAs) show promise as potential predictors of clinical events. This study assessed long-term clinical outcomes using ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI (ISRCTN76413758) and fluorine-18 sodium fluoride ([18F]NaF) PET/CT (NCT02229006).

Methods: In two prospective multicentre co-enrolled observational cohort studies of patients with asymptomatic AAAs, evaluation of aortic wall inflammation using USPIO-enhanced MRI in 338 patients was followed by [18F]NaF PET/CT in a subgroup 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.

Results: In 338 predominantly elderly (mean(s.d.) age of 73.5(7.2) years) men (85.2%) with a mean(s.d.) aneurysm diameter of 49.5(7.3) mm, aneurysm expansion was increased in patients with USPIO enhancement (median of 3.3 (interquartile range (i.q.r.) 2.0-4.6) versus 2.5 (i.q.r. 1.4-3.6) mm/year; P = 0.002) or high [18F]NaF uptake (median of 4.0 (i.q.r. 2.6-5.4) versus 1.9 (i.q.r. 0.9-3.0) mm/year; P < 0.001), even when adjusted for hypertension, smoking, and baseline AAA diameter (P = 0.038 and P = 0.003). After a median follow-up of 102 (i.q.r. 58-119) months, 62.7% of patients met the composite endpoint of rupture or repair, with high [18F]NaF uptake associated with a more than two-fold higher risk (72% versus 36%; log rank P = 0.002). There was no association between USPIO enhancement and future rupture or repair.

Conclusion: 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 at the greatest risk of AAA progression and may help inform further research to determine optimal surveillance intervals.