gms | German Medical Science

Objective: The estimation of the individual rupture risk of intracranial aneurysms (IA) remains challenging. Structural integrity of IA is predominantly determined by collagen type I, the main molecular constituent in IA. A hallmark of the pathogenesis of IA is ongoing collagen remodelling in the IA wall and synthesis of immature/structural deficient collagen. To date, in vivo biomarkers for molecular instability in IA are lacking. We endeavoured to detect breakdown products of collagen derived from human IA in serum as potential surrogates for the instability of the IA wall.

Methods: Two blood samples from intra-aneurysmal (intra-IA) and the femoral artery were obtained during catheter angiography from patients undergoing endovascular repair of their IA. Additionally, venous blood samples were obtained from IA patients as well as control subjects (no known presence of IA). Detection of collagen breakdown products cross-linked C-telopeptide of collagen type I (CTx) was performed by serum immunoassay. Recently grown or ruptured IA were defined as unstable. T-test, correlation, logistic regression and receiver operating characteristic (ROC) analyses were performed.

Results: Between 10/2018 and 11/2019 27 IA patients (15 female, 12 male) with 57.3±12.2 years were included. There were 8 unruptured, 19 ruptured and 5 stable, 22 unstable IA. 18 control subjects (7 female, 11 male) with 45.4±16.6 years were included. Intra-IA CTx levels were higher in ruptured compared to unruptured IA (0.63±0.28ng/ml vs. 0.35±0.24ng/ml, p=0.02) and higher in unstable compared to stable IA (0.62±0.28ng/ml vs. 0.27±0.10ng/ml, p=0.01). Intra-IA CTx levels predicted IA rupture in univariate analysis (likelihood ratio (LR) 6.6, p=0.01; OR 275.4, 95% CI 1.1-72395.9) and after including age, smoking, hypertension in multivariate analysis (LR 5.6, p=0.02; OR 223.0, 95% CI 0.8-63843.5). ROC analysis demonstrated a good test accuracy (AUC 0.72, 95% CI 0.45-0.98) for intra-IA CTx levels with a threshold ≥ 0.464 ng/ml for IA rupture. Venous CTx levels were higher in IA patients compared to controls (0.33±0.18ng/ml vs. 0.20±0.08ng/ml, p=0.004). There was a strong correlation between intra-IA and venous CTx levels (r=0.53, p=0.004) and between CTx levels from intra-IA and femoral artery (r=0.95, p<0.001).

Conclusion: Our pilot study indicates that arterial and potentially venous CTx levels could serve as a novel indicator for increased instability in IA patients for assessment of their IA.