{"doi":"10.1101/2023.05.14.23289966","title":"Associations of rest-activity rhythm disturbances with stroke risk and post-stroke adverse outcomes","abstract":"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.","journal":"medRxiv","year":2023,"id":390995,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":694274,"name":"Xi Zheng","orcid":"0009-0001-9847-7063","position":1,"is_corresponding":false},{"id":1163769,"name":"Sarah N. Baker","orcid":null,"position":2,"is_corresponding":false},{"id":396850,"name":"Peng Li","orcid":"0000-0002-4684-4909","position":3,"is_corresponding":false},{"id":249994,"name":"Frank A. J. L. Scheer","orcid":"0000-0002-2014-7582","position":4,"is_corresponding":false},{"id":1117495,"name":"Ricardo de Carvalho Nogueira","orcid":"0000-0003-3309-3760","position":5,"is_corresponding":false},{"id":396849,"name":"Kun Hu","orcid":"0000-0003-0350-3132","position":6,"is_corresponding":false},{"id":582193,"name":"Lei Gao","orcid":"0000-0003-1476-1460","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"37292791","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}