Accelerometer-derived rest-activity rhythms, genetic risk, and chronic inflammatory markers and the risk of abdominal...

Disrupted rest-activity rhythm (RAR), an accelerometer-derived measure of the strength and temporal organization of daily behavioral rhythms, has been linked to multiple adverse health outcomes. Given that the development of abdominal aortic aneurysm (AAA) involves chronic inflammation, extracellular matrix degradation, and vascular smooth muscle cell dysfunction, attenuated rest-activity rhythms (RAR) may be associated with AAA risk. However, prospective evidence on this association remains limited.

The primary analysis included 78,282 UK Biobank participants who completed accelerometer monitoring between 2013 and 2015. Thirteen parametric and nonparametric RAR parameters were derived. Cox proportional hazards models estimated associations between RAR parameters and AAA incidence, as well as potential interactions and joint effects with other risk factors. Causal mediation analysis examined the mediating role of inflammatory markers. An XGBoost-based survival model evaluated variable importance, and SHapley Additive exPlanations (SHAP) interpreted feature contributions.

During a mean follow-up of 10.1 years, 229 AAA cases were recorded. Lower RAR parameters, particularly relative amplitude (RA), M10, amplitude, and mesor, were significantly associated with higher AAA risk [lowest vs. highest tertile HRs: RA 1.49 (95% CI 1.03-2.15); M10 1.51 (1.05-2.18); amplitude 1.58 (1.09-2.30); mesor 1.46 (1.04-2.14)]. Although no significant interactions were observed, individuals with weaker RAR combined with current smoking or high polygenic risk had markedly increased AAA risk. Mediation analysis indicated that neutrophil and monocyte counts explained about 5-6% of the RAR-AAA association. In the XGBoost model, beyond age, male sex, and PRS as dominant predictors, mesor, RA, and M10 emerged as meaningful contributors to AAA risk prediction.

Accelerometer-derived RAR parameters are strongly associated with the risk of developing AAA. Integrating RAR measures with genetic and traditional risk factors may improve risk stratification and provide novel insights for preventive strategies against AAA.