Accelerometer-measured circadian alignment predicts all-cause and cardiovascular mortality in middle-aged and older...

Circadian alignment plays a key role in cardiometabolic regulation. We examined whether accelerometer-derived alignment metrics independently predict all-cause and cardiovascular mortality in middle-aged and older adults.

We included 4,814 U.S. adults aged ≥45 years from the 2011-2014 NHANES cycles. Circadian alignment was measured once for each participant during their examination year via wrist-worn accelerometer data. Two phasor metrics-magnitude (synchronization strength) and angle (timing deviation)-were categorized into quartiles. Mortality was ascertained through linkage to the National Death Index, with follow-up through December 31, 2019. All-cause and cardiovascular disease (CVD)-specific mortality rates were analyzed via weighted Cox proportional hazards regression, Fine and Gray's competing risk models, and restricted cubic splines to account for nonlinear associations.

Over 31,280 person-years, 736 deaths occurred (235 CVD-related deaths). Compared with those in the highest quartile (Q4), participants in the lowest quartile of phasor magnitude (Q1) had a significantly greater risk of all-cause mortality (HR, 1.70; 95% CI, 1.08-2.68). A U-shaped association was observed for the phasor angle: both advanced (Q1) and most delayed (Q4) timing were linked to elevated all-cause mortality risk, with Q2 representing optimal alignment. For CVD-specific mortality, advanced timing (Q1 vs. Q2) was associated with a 68% increased risk (HR, 1.68; 95% CI, 1.09-2.60). Restricted cubic splines confirmed nonlinear relationships.

A lower phasor magnitude and both advanced and delayed phasor angles were associated with higher all-cause and CVD-specific mortality. Circadian metrics may serve as biomarkers to inform wearable-based monitoring and behavioral interventions.