Association of estimated cardiorespiratory fitness with circadian syndrome: A cross-national analysis of two large aging cohorts

Promoting healthy aging requires identifying modifiable factors that can preserve physiological regulation. Cardiorespiratory fitness (CRF), a key pillar of healthspan, and Circadian Syndrome (CircS), an emerging marker of systemic dysregulation, are both strongly linked to health outcomes, yet their direct relationship is unknown. This study aimed to investigate the cross-sectional and longitudinal associations between estimated CRF (eCRF) and CircS in two large, distinct aging populations. This population-based study utilized data from the China Health and Retirement Longitudinal Study (CHARLS; n=3,116) and the English Longitudinal Study of Ageing (ELSA; n=7,039). Associations were evaluated using logistic regression for prevalent CircS and Cox proportional hazards models for incident CircS. Covariate selection for these models was guided by a Directed Acyclic Graph (DAG). Restricted cubic splines were used to model non-linear associations, and stratified analyses were conducted to identify potential effect modifiers. A total of 10,155 participants were included. Cross-sectionally, higher eCRF was robustly associated with lower odds of prevalent CircS in both CHARLS (OR for high vs. low: 0.12, 95%CI 0.10-0.15) and ELSA (OR: 0.16, 95%CI 0.14-0.18), with a linear dose-response in CHARLS but a non-linear one in ELSA. Longitudinally, higher baseline eCRF was associated with a lower risk of incident CircS in both the CHARLS (HR: 0.38, 95%CI 0.25-0.56) and the ELSA cohorts (HR: 0.45, 95%CI 0.36-0.56). The association in ELSA was significantly modified by sex (P-interaction<0.001), being stronger in females; this interaction was observed in both cross-sectional and longitudinal analyses. Higher eCRF is associated with both a lower prevalence and reduced long-term incidence of CircS in both Chinese and English older adults. However, the characteristics of this association, including dose-response patterns and modification by sex, appear to be population-dependent. This graphical abstract illustrates the association between estimated cardiorespiratory fitness (eCRF) and systemic health. The left panel depicts the 'Healthy State' associated with high eCRF, characterized by robust cardiovascular function, efficient neuromuscular control, and optimal brain health. The right panel depicts the 'Risk State' associated with low eCRF, which conceptually represents Circadian Syndrome. This state is marked by systemic dysregulation, including vascular dysfunction, increased visceral adiposity, impaired pancreatic function, and neuroinflammation, collectively contributing to a higher risk profile for adverse health outcomes in aging. • Higher cardiorespiratory fitness is linked to lower Circadian Syndrome risk. • The link is linear in Chinese adults, but non-linear in English cross-section. • In English adults, the fitness-syndrome link is markedly stronger in females. • Findings are robust across both cross-sectional and longitudinal analyses.