Changes in monocyte subsets can predict the risk of AAA and are surrogate markers for AAA morphology in patients with late-stage disease

Background Monocytes play a pivotal role in pathology of abdominal aortic aneurysm (AAA) and can display an immunophenotypic heterogeneity with functionally distinct subpopulations. Alterations in monocyte subsets have been described in CVD, and some are associated with cardiovascular risk, but their profile in AAA is poorly understood. Aim We aimed to comprehensively define associations of circulating monocyte phenotypes with AAA risk and AAA morphology. Methods Monocyte subsets (CD14++CD16−; CD14++/CD16+; CD14+/CD16++) were analyzed in a prospective, observational study in patients with AAA (n=34) and varicose veins (n=34) by using flow cytometry. Results Classical monocytes were 1.6-fold lower ( P =0.001) in AAA, while intermediate and non-classical monocytes were 1.8 ( P =0.019) and 1.9-fold ( P =0.025) higher in AAA, respectively. The differences remained significant after adjusting for age, sex and peripheral artery disease. A lower proportion of classical monocytes (HR: 0.73, P =0.002) and increases in intermediate (HR: 1.41, P =0.006) and non-classical monocytes (HR: 1.54, P =0.030) were associated with a higher risk of AAA. Non-classical monocytes showed an inverse correlation with AAA diameter (Pearson correlation =-0.64, P =0.001) and AAA volume (Pearson correlation =-0.50, P= 0.003). Conclusion The present study revealed age- and sex-independent shifts in monocytes, all of which were associated with risk of AAA disease. Non-classical monocytes were inversely correlated with AAA diameter and volume and thus may be surrogate markers for AAA morphology. What’s new? Classical monocytes are lower in patients with late-stage AAA. Non-classical monocytes showed the strongest increase in AAA disease. A reduction in classical monocytes is associated with increased risk of AAA. An increase in non-classical and intermediate monocytes is associated with an increased risk of AAA. Lowering in non-classical monocytes may be a surrogate marker for AAA morphology, particlarly AAA volume. Intermediate monocytes showed a positive correlation with the thickness of the intraluminal thrombus. What are the clinical implications? The increase in non-classical monocytes could be a novel surrogate marker for AAA volume, which could be useful when AAA diameter is insufficient or to monitor a saccular AAA, as there is a weaker correlation between diameter and risk of rupture in this type of AAA. The decrease in classical monocytes could be a useful surrogate marker for AAA volume and provide additional information on AAA diameter. Monocyte shifts and their association with AAA disease may be relevant for the diagnosis of AAA and should be verified in larger cohorts. The mechanisms behind the decrease in classical monocytes and the increase in intermediate and non-classical subsets should be investigated in further in vitro studies as they offer therapeutic potential.