Circadian disruption is associated with advanced cardio-kidney-metabolic syndrome in overweight and obese adults: evidence from the NHANES database

Circadian disruption and obesity are increasingly recognized as key contributors to cardio-kidney-metabolic (CKM) syndrome. Yet, the extent to which circadian misalignment accelerates progression to advanced CKM stages in overweight and obese adults remains insufficiently defined. This study utilized both cross-sectional and longitudinal data from the National Health and Nutrition Examination Survey (NHANES) (2011–2014), focusing on overweight and obese adults aged 20 years and older. Circadian alignment was assessed by evaluating light-activity synchronization through phasor analysis, measuring phasor magnitude and acrophase, and the phasor magnitude was categorized into quartiles for subsequent statistical analysis. CKM stages (0–4) were used to represent progressive disease pathophysiology, with advanced stages (3 or 4) compared to nonadvanced stages (0, 1, or 2). Cross-sectional models were used to assess the association between circadian alignment and advanced CKM stages, and longitudinal survival models were applied to evaluate its associations with all-cause, cardiovascular, and premature mortality. A total of 5,335 overweight and obese participants (median follow-up: 6.83 years) were included, representing approximately 111 million U.S. adults when survey weights were applied. After adjusting for age, sex, race, education, household income, smoking, alcohol consumption, hypertension, and diabetes, individuals with the lowest phasor magnitude—reflecting poor synchronization between light exposure and activity cycles—had significantly higher risks of advanced CKM stages (OR = 1.77, 95% CI: 1.17–2.68), all-cause mortality (OR = 2.12, 95% CI: 1.52–2.95), cardiovascular mortality (OR = 7.63, 95% CI: 2.82–20.63), and premature mortality (OR = 1.89, 95% CI: 1.07–3.36). Subgroup analyses further revealed that the associations between low phasor magnitude and both all-cause and cardiovascular mortality were stronger in older adults and men. Among overweight and obese individuals, lower phasor magnitude—indicating poor synchronization between light and activity cycles—was associated with higher risks of advanced CKM stages and increased mortality. These findings suggest that quantifying circadian disruption is important, and that interventions to enhance circadian alignment may help reduce CKM-related risks.