Abstract

Background: Patients known to have abdominal aortic aneurysms (AAAs) undergo surveillance imaging to predict both the risk for acute aortic syndromes including aortic dissection and aortic rupture, and the need for surgical intervention. Aortic rupture is a feared consequence of rapidly expanding AAAs. Aims: A blood biomarker that predicts risk for AAA and distinguishes slow from fast AAA growth does not exist but could be a valuable tool for risk stratification. We recently reported systemic levels of the gut microbe-generated metabolite trimethylamine N-oxide (TMAO) are associated with the presence of AAA in humans, and directly contribute to AAA progression in animal models. Methods: We leveraged access 805 patients in two cohorts from Europe (n=237) and the United States (n=658) undergoing serial aortic imaging surveillance. Blood TMAO concentration was measured by stable isotope dilution mass spectrometry. Results: TMAO was positively associated with larger baseline and follow-up abdominal aortic diameter beyond traditional factors (Adjusted OR 3.87, 95% CI, 2.70-5.58, P<0.001). In addition, TMAO predicted rapid AAA growth (HR 1.81, 95%CI, 1.23-2.67, P=0.0029). When TMAO was added to a predictive model of traditional risk factors for AAA, we saw a significant improvement in the net reclassification index (NRI, 0.43, P < 0.001; C statistic, 0.77 (0.72–0.81) with TMAO vs. NRI 0.73 (0.69–0.78) without TMAO, P =0.005). Finally, including TMAO in a predictive model for assessing need for surgical intervention among AAA patients significantly improved the prognostic performance of the model (NRI, 0.44, P < 0.001; C statistic, 0.78 (0.73–0.82) with TMAO vs. 0.75 (0.70–0.79) without TMAO, P =0.004) (Fig. 1). Conclusions: Elevated TMAO levels predict increased risk of AAA, and identify patients with fast-growing AAA and those who may benefit from early surgical intervention to prevent acute aortic syndromes.