Abstract 27: Chronotype, Life’s Essential 8, and Risk of Cardiovascular Disease: A Prospective Cohort Study in UK Biobank

Introduction: Individuals with evening chronotype often experience circadian misalignment, which may disrupt health behaviors and circadian regulation of cardiometabolic functions such as blood pressure and heart rate. However, the association of chronotype with cardiovascular disease (CVD) and the interplay with other CVD risk factors are not fully understood. Hypothesis: We assessed the hypothesis that individuals with an evening chronotype, compared to those with a morning chronotype, have a poorer cardiovascular health as measured by the Life’s Essential 8 (LE8), and consequently an increased CVD risk. We further explored if the associations differed by sex. Methods: We conducted a prospective study in the UK Biobank among 477,878 adults aged 39-74 years and free of CVD at baseline in 2006-2010. Chronotype was self-reported using a single representative question from the Morningness-Eveningness Questionnaire. The LE8 score was calculated based on 8 modifiable CVD risk factors, and ranged from 0 to 100 with higher scores indicating better cardiovascular health. Incident CVD was defined as first myocardial infarction (MI) or stroke leading to hospitalization or death, identified via validated algorithms that mapped national medical records and death certificates to ICD-10 codes until May 2022. We used Cox proportional hazards models to estimate the association between chronotype and CVD risk. Models were adjusted for demographics, shift work, and family history of CVD. We applied causal mediation framework to decompose the total chronotype-CVD effect into estimated natural direct effect (i.e., independent of LE8) and natural indirect effect (i.e., mediated by LE8; NIE). Results: Participants with a “definite evening” chronotype were 75% more likely to have a low LE8 score (<50) compared to “intermediate” type (prevalence ratio 95% CI: 1.67, 1.84). This association was notably stronger among women ( P -interaction: 0.0001). Over 12.7 years of follow-up, there were 27,346 documented incident CVD events (17,180 MI; 11,329 stroke). The hazard ratio (HR) for total CVD was 1.03 (95% CI: 1.00, 1.06) for the “definite morning” and 1.15 (95% CI: 1.10, 1.20) for “definite evening” compared with “intermediate” chronotype ( P -trend: 0.06). This association was stronger in women ( P -interaction: 0.05), and similar for MI and stroke. The NIE of the chronotype-CVD association comparing “definite evening” to “intermediate” was 1.11 (95% CI: 1.09, 1.13), equivalent to 95% of the association being mediated by LE8. Conclusions: Evening chronotype was associated with a modest increase in CVD risk, compared to intermediate chronotype, which appeared to be mainly explained by overall poor cardiovascular health. Our results suggest potential benefits of targeted interventions in evening chronotype for CVD prevention. Ongoing work is exploring potential effect modification by night shift work.