AIMS: This study prospectively evaluated the associations between metabolic syndrome (MetS), circadian syndrome (CircS) and mortality from major diseases.
METHODS: We conducted prospective analyses using data from two large cohorts: NHANES (n = 14,727 for MetS; 13,799 for CircS, aged ≥ 20 years) and the UK Biobank (n = 404,028 for MetS; 376,236 for CircS, aged ≥ 40 years). We assessed associations between MetS, CircS, and all-cause, cardiovascular, and cancer mortality, using Cox proportional hazards models. Model performance was compared using C-index, Brier Score, AIC, and BIC.
RESULTS: In NHANES, the prevalences of MetS and CircS were 41.1 % and 31.7 %, respectively, while in UKB, they were 29.9 % and 17.6 %, respectively. In fully adjusted models, MetS was significantly associated with a 21 % increase in all-cause mortality, and CircS was significantly associated with a 34 % increase in all-cause mortality and a 65 % increase in heart diseases mortality in the NHANES cohort; both MetS and CircS were significantly associated with increased risks of mortality from heart diseases (MetS: HR = 1.68; 95 % CI, 1.58-1.79; CircS: HR = 1.78; 95 % CI, 1.66-1.90), cancers (MetS: HR = 1.19; 95 % CI, 1.15-1.24; CircS: HR = 1.24; 95 % CI, 1.19-1.29), CVD (MetS: HR = 1.56; 95 % CI, 1.48-1.64; CircS: HR = 1.66; 95 % CI, 1.56-1.75), ischemic heart disease (MetS: HR = 1.81; 95 % CI, 1.68-1.96; CircS: HR = 1.93; 95 % CI, 1.79-2.09), stroke (MetS: HR = 1.36; 95 % CI, 1.21-1.53; CircS: HR = 1.42; 95 % CI, 1.24-1.61), and all-cause mortality (MetS: HR = 1.30; 95 % CI, 1.26-1.33; CircS: HR = 1.42; 95 % CI, 1.38-1.46) in the UKB cohort. CircS showed stronger associations with all mortality outcomes across both cohorts. Subgroup analyses revealed stronger associations in middle-aged adults, but weaker associations in those ≥ 70 years. CircS-based models consistently outperformed MetS-based models in terms of AIC and BIC.
CONCLUSIONS: CircS may provide a more comprehensive and interpretable framework for mortality risk prediction than MetS. Its potential incorporation into clinical and public health practice warrants further investigation.
