Sleep–wake circadian organisation (relative amplitude) and incident cardiovascular disease in UK Biobank

Abstract

Disrupted sleep–wake organisation is a behavioural marker of circadian dysregulation and may contribute to cardiovascular disease (CVD). Prospective evidence using objective, wearable-derived circadian rhythmicity measures beyond total physical activity (PA) volume and sleep duration remains limited. We analysed 89,253 UK Biobank participants without prevalent CVD who provided valid 7-day wrist-worn accelerometer data (2013–2015). Sleep–wake circadian organisation was quantified using relative amplitude (RA), derived non-parametrically from the contrast between the most active 10-h (M10) and least active 5-h (L5) periods. Incident CVD was ascertained via linked hospital and mortality records. Cox models estimated hazard ratios (HRs) adjusting for sociodemographic factors, lifestyle factors, cardiometabolic risk factors, self-reported sleep duration, and accelerometer-derived total PA volume. Over a median follow-up of 9.6 years, 5,793 incident CVD events occurred. Higher RA was associated with lower CVD risk after full adjustment (per 1-SD higher RA: HR 0.91, 95% CI 0.89–0.94). Participants in the lowest versus highest RA quartile had a 29% higher CVD risk (HR 1.29, 95% CI 1.17–1.42). RA modified excess risk associated with low PA volume (inactive) (P-interaction=0.028): inactive individuals with high RA (robust rhythm) showed no elevated risk compared with the high-PA/high-RA group (HR 1.00, 95% CI 0.91–1.09). Associations were stronger in adults aged ≥60 years (P-interaction<0.001). Wearable-derived sleep–wake circadian organisation (RA) was associated with incident CVD beyond total activity volume and sleep duration. More robust 24-h behavioural organisation may help identify higher- versus lower-risk individuals within low-activity adults and may complement activity-based prevention strategies, particularly in older adults.Figure 1.Sleep–wake RA and incident CVDFigure 2.Joint RA–PA and incident CVD