Research questions
1.Do accelerometer-derived circadian dysregulation features (e.g., lower stability, lower amplitude, higher fragmentation, phase shifts) predict incident angina and angina-specific mortality?
2.Does a sleep-disorder-burden index derived from the sleep questionnaire add to risk stratification, alone and jointly with objective circadian dysregulation (a combined “rhythm-symptom” phenotype)?
3.Is autonomic vulnerability (lower HRV) an effect modifier of the circadian dysregulation-angina association, and do proteomic and imaging markers support biological pathways (e.g., inflammation/endothelial/metabolic/neuro-modulatory axes)?
Research objectives
Build an interpretable and reproducible circadian dysregulation phenotype; estimate associations with incident angina using Cox models (time zero at accelerometer completion) and evaluate angina-specific mortality using competing-risk and/or cause-specific models; quantify absolute risk differences; and conduct mechanism-oriented analyses in overlapping subsets with HRV, proteomics, and imaging. Robustness analyses will address reverse causation and representativeness (e.g., excluding early events; season/weekend sensitivity).
Scientific rationale for the research
Circadian disruption may increase cardiovascular vulnerability through autonomic dysregulation and inflammatory/endothelial/metabolic pathways, potentially precipitating angina and adverse outcomes. Objective accelerometer-derived rhythms reduce reporting bias and, combined with symptom burden and multi-omics/imaging, can support a “risk-mechanism-actionable targets” framework.