Abstract Body: Introduction: Circadian rhythm disruption is prevalent in older adults and has been linked to autonomic dysfunction, chronic inflammation, and metabolic dysregulation, which are key pathological processes implicated in the development of heart failure (HF). Despite these shared mechanistic pathways, the association between disrupted circadian rest-activity rhythms (RARs) and HF remains unknown. This longitudinal study investigated the association between circadian RARs and incident HF among older adults from the Atherosclerosis Risk in Communities (ARIC) study.
Hypothesis: Disrupted circadian RARs are associated with increased risk of incident HF.
Methods: We included participants free of HF at visit 6 (2016-17) when RARs were assessed using an accelerometer embedded in the Zio® XT ECG monitor. RARs were quantified using three nonparametric indices: relative amplitude (rhythm strength), interdaily stability (rhythm regularity), and intradaily variability (rhythm fragmentation). All three RAR measures were standardized to a mean of 0 and a standard deviation of 1 to enable direct comparison of effect sizes across metrics. Cox proportional hazards regression was used for analysis.
Results: We analyzed data from 2,216 participants (median age, 78 years) with RAR evaluation over a median (IQR) of 13.8 (13.1-14.0) days of uninterrupted monitoring. During a median (IQR) follow-up of 6.6 (5.0-7.0) years, 294 (13.3%) participants developed incident HF. Lower relative amplitude, indicating reduced circadian rhythm strength, was significantly associated with elevated HF risk. After adjusting for baseline characteristics and prevalent cardiovascular disease, each one-standard-deviation decrease in relative amplitude was associated with a 36% (HR (95% CI), 1.36 (1.19-1.55)) higher risk of HF (Table 1). Compared to those in the highest tertile, participants in the lowest tertile had a more than 2-fold higher risk of developing HF, while those in the middle tertile had a 64% higher risk. However, the risk of incident HF was not significantly different across tertiles of interdaily stability and intradaily variability.
Conclusions: In this longitudinal study of community-dwelling older adults without prevalent HF, lower circadian rhythm strength (i.e., lower relative amplitude) was significantly associated with higher risk of developing HF. Circadian rhythm disruption may be a novel risk marker for early identification of individuals at elevated risk of HF.