A Comprehensive Longitudinal Evaluation of Pre-operative and Post-operative Plasma Matrix Metalloproteinases for Identifying Patients at Increased Risk of Endoleak after Endovascular Aneurysm Repair

OBJECTIVE: To evaluate whether plasma concentrations of a comprehensive panel of matrix metalloproteinases (MMPs), measured at baseline and during follow up, are associated with the development of endoleak after endovascular aortic repair (EVAR), and to establish clinically relevant thresholds for post-operative risk stratification. METHODS: This was a prospective, single centre, observational cohort study including 100 consecutive patients undergoing elective infrarenal EVAR between July 2022 and July 2024. Plasma levels of nine MMP isoforms (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13) were quantified using an enzyme linked immunosorbent assay at baseline, seven days, six and 12 months. Endoleak was diagnosed on scheduled computed tomography angiography at one, six, and 12 months, independently adjudicated by two radiologists blinded to biochemical data. Associations between MMP concentrations and endoleak were analysed with independent t tests, effect sizes, and multivariable logistic regression. Predictive accuracy was assessed with receiver operating characteristic curves, and optimal cutoff values were derived using the Youden index. RESULTS: During follow up, 24 patients developed endoleak. Pre-operatively, MMP-1 and MMP-2 levels were statistically significantly higher in the endoleak group (p < .010). At seven days, MMP-1 and MMP-9 were the strongest discriminators (p < .001), while at 12 months, MMP-9 and MMP-10 remained independently associated with endoleak (p < .010). Combined models consistently outperformed individual biomarkers, with areas under the receiver operating characteristic curve of 0.880 (MMP-1 + MMP-2, baseline), 0.827 (MMP-1 + MMP-9, seven days), and 0.861 (MMP-9 + MMP-10, 12 months). Clinically relevant cutoff values were identified: ∼15 μg/mL for MMP-1 at baseline, ∼42 μg/mL for MMP-9 at seven days, and ∼2 μg/mL for MMP-10 at 12 months. CONCLUSION: A dynamic biomarker profile, MMP-1 and MMP-2 pre-operatively, MMP-1 and MMP-9 early post-operatively, and MMP-9 and MMP-10 at late follow up, accurately identified patients at risk of endoleak. Incorporating MMP measurements into follow up protocols may complement imaging and enable personalised surveillance after EVAR.