Joint associations of device-measured physical activity and sleep duration with incident major adverse cardiovascular events: prospective analysis of the UK Biobank

BackgroundThe interaction between physical activity and sleep with cardiovascular disease remains poorly understood, despite both being key risk factors. This study investigated the independent and joint associations of device-measured physical activity and sleep duration with incident major adverse cardiovascular events (MACE). MethodsProspective analysis of UK Biobank participants who wore a wrist-based accelerometer for seven days. Open-source machine learning algorithms derived daily step count and overnight sleep duration. The outcome was incident MACE (cardiovascular death, non-fatal myocardial infarction or stroke, or revascularisation procedure), identified through electronic health record linkage. Cox proportional hazards models were used to examine independent and joint associations of median daily step count (low [<7,500], intermediate [7,500-11,000], high [>11,000]) and median overnight sleep duration (short [<6.5 hours], intermediate [6.5-7.5 hours], long [>7.5 hours]) with incident MACE. FindingsAmong 88,012 participants (mean age 62{middle dot}2 years [SD 7{middle dot}8]), 3,817 were diagnosed with MACE during follow-up (median 7{middle dot}9 years [IQR 7{middle dot}3-8{middle dot}4]). Fewer daily steps and short sleep duration were independently associated with a higher risk of MACE, but there was no evidence of an interaction between step count and sleep duration (Pinteraction = 0{middle dot}42). Compared with the reference group - participants with high step count and intermediate sleep duration - the highest risk of MACE was observed in participants with both low step count and short sleep duration (HR: 1{middle dot}84, 95% CI: 1{middle dot}62-2{middle dot}10). InterpretationThe results of this study show that higher levels of physical activity do not fully attenuate the higher risk of cardiovascular disease associated with short sleep duration, reinforcing the importance of sufficient levels of both physical activity and sleep for the prevention of cardiovascular disease. FundingWellcome Trust (223100/Z/21/Z). CopyrightFor the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched the Medline and Embase databases in June 2025 for articles published in English from database inception to June 18th, 2025. Key search terms included physical activity, sleep, and cardiovascular disease, along with their synonyms, using both MeSH and free-text terms (Table S1). Previous studies have reported mixed evidence for an interaction between physical activity and sleep duration with incident cardiovascular mortality (Table S2 and S3). Some found that higher levels of physical activity attenuated the higher risk associated with abnormal sleep duration, whereas others did not replicate these findings. Many previous studies relied on self-reported measures of physical activity and sleep duration, and reported physical activity metrics that are not easily interpretable. Moreover, by focusing exclusively on cardiovascular mortality, they included relatively few events. Added value of this studyTo our knowledge, this prospective cohort study is the first to investigate the joint associations of step count and sleep duration with incident major adverse cardiovascular events. This study used accelerometer data from over 88,000 UK Biobank participants, with the outcome identified through electronic health record linkage. We adjusted for a broad range of key covariates and addressed potential reverse causation by excluding participants with latent or prevalent cardiovascular disease. Although both fewer daily steps and short sleep duration were independently associated with a higher risk of major adverse cardiovascular events, we found no evidence of an interaction between step count and sleep duration. Implications of all the available evidencePhysical activity and sleep are essential components of daily life. They are closely linked within the 24-hour cycle and are both associated with cardiovascular disease. The results of this study show that higher levels of physical activity do not fully attenuate the higher risk of cardiovascular disease associated with short sleep duration, reinforcing the importance of sufficient levels of both physical activity and sleep for the prevention of cardiovascular disease.