Synergistic impact of rest-activity circadian rhythms and physical activity on all-cause and cardiovascular mortality

BACKGROUND: This study investigated the independent and joint associations of rest-activity circadian rhythms (RACRs) and physical activity (PA) with all-cause and cardiovascular mortality, and explored the potential role of accelerated biological aging. METHODS: We included 6621 adults from NHANES 2011-2014. RACR parameters were derived from wrist-worn ActiGraph GT3X+ data. Accelerated biological aging was assessed using Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel). Cox proportional hazards models were applied to investigate the associations of RACRs and PA with all-cause and cardiovascular mortality. Exploratory mediation analyses were used to explore the associations between accelerated biological aging, RACRs, and mortality risks. RESULTS: Over a median follow-up of 6.75 years, 518 all-cause deaths and 165 cardiovascular deaths were recorded. Compared with weak RACRs and inadequate PA, participants with strong RACRs and adequate PA had significantly lower risks of all-cause mortality (HR: 0.35, 95% CI: 0.24 to 0.51; p < .001) and cardiovascular mortality (HR: 0.25, 95% CI: 0.14 to 0.45; p < .001). In exploratory analyses, PhenoAgeAccel accounted for an estimated 13.55% (p < .001) and 21.67% (p = .002) of the associations between RACRs and all-cause and cardiovascular mortality, respectively, while BioAgeAccel accounted for an estimated 5.06% (p < .001) and 8.06% (p = .004). CONCLUSIONS: Disrupted RACRs are associated with higher mortality risks that could be attenuated by adequate physical activity. Exploratory analyses suggest that the associations between RACRs and mortality may be mediated in part by accelerated biological aging, but additional studies are needed to test this hypothesis.