Abstract
BACKGROUND: Almost all biological and disease processes are influenced by circadian clocks and display ∼24-hour rhythms. Disruption of these rhythms may be an important novel risk factor for stroke. We evaluated the association between 24-h rest-activity rhythm measures, stroke risk, and major post-stroke adverse outcomes. METHODS: In this cohort study, we examined ∼100,000 participants in the UK Biobank (44-79 years old; ∼57% females) who underwent an actigraphy (6-7 days) and 5-year median follow-up. We derived: (1) most active 10 hours activity counts ( M10 ) across the 24-h cycle and the timing of its midpoint ( M10 midpoint ); (2) the least active 5 hours counts ( L5 ) and its midpoint timing ( L5 midpoint ); (3) relative amplitude ( RA ) - (M10-L5)/(M10+L5); (4) interdaily stability (IS): stability and (5) intradaily variability (IV), fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (i) incident stroke (n=1,652); and (ii) post-stroke adverse outcomes (dementia, depression, disability, or death). RESULTS: Suppressed RA (lower M10 and higher L5) was associated with stroke risk after adjusting for demographics; the risk was highest in the lowest quartile [Q1] for RA (HR=1.62; 95% CI:1.36-1.93, p <0.001) compared to the top quartile [Q4]. Participants with later M10 midpoint timing (14:00-15:26, HR=1.26, CI:1.07-1.49, p =0.007) also had a higher risk for stroke than earlier (12:17-13:10) participants. A fragmented rhythm (IV) was also associated with a higher risk for stroke (Q4 vs. Q1; HR=1.27; CI:1.06-1.50, p =0.008), but differences in the stability of rhythms (IS) were not. Suppressed RA was associated with an increased risk of unfavorable post-stroke outcomes (Q1 vs. Q4; 1.78 [1.29-2.47]; p <0.001). All the associations were independent of age, sex, race, obesity, sleep disorders, cardiovascular diseases or risks, and other morbidity burdens. CONCLUSION: Suppressed 24-h rest-activity rhythm may be a risk factor for stroke and an early indicator of major post-stroke adverse outcomes.