Association Between Rest-Activity Rhythm and Cardiovascular Disease, Cardiovascular Mortality, and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Background

Disruption in rest-activity rhythm (RAR) is an emerging risk factor for cardiovascular disease (CVD) and mortality, but the strength of evidence is unclear. Therefore, we conducted a systematic review and meta-analysis to assess associations between RAR characteristics and cardiovascular disease incidence or prevalence, cardiovascular mortality, and all-cause mortality.

Methods

A systematic search was conducted in PubMed, Web of Science, Cochrane Library, and Embase for cohort or cross-sectional studies published up to August 2025. The exposure variables were nonparametric RAR parameters, including interdaily stability (describing day-to-day stability of the RAR), intradaily variability (a measure of RAR fragmentation), and relative amplitude (indicating robustness or strength of the RAR). The primary outcomes were cardiovascular mortality and all-cause mortality. The secondary outcomes included cardiovascular disease prevalence and incidence.

Results

Seven studies involving 109 365 participants were included. Pooled results showed that higher intradaily variability was associated with a significantly increased risk of all-cause mortality (hazard ratio [HR], 1.05 [95% CI, 1.02-1.09]) and cardiovascular disease prevalence (odds ratio, 1.73 [95% CI, 1.21-2.47]). Lower relative amplitude was significantly associated with higher cardiovascular mortality (HR, 1.50 [95% CI, 1.13-1.98]) and all-cause mortality (HR, 1.46 [95% CI, 1.27-1.68]). Interdaily stability showed no significant associations with any outcome.

Conclusions

Measures of disrupted rest-activity rhythms were associated with increased cardiovascular mortality, and all-cause mortality. These findings support using RAR metrics as early, noninvasive risk indicators. Future work should investigate whether appropriately timed physical activity and sleep, as well as other interventions targeting RAR can mitigate cardiovascular risk.