BACKGROUND AND AIMS Cardiovascular-kidney-metabolic (CKM) syndrome is a novel consensus defined by its multi-systemic and progressive nature. Circadian rhythm is a critical modulator of metabolic health. However, no previous studies assessed the associations between circadian alignment and CKM risk and outcomes.

METHOD This analysis utilized 2011-2014 NHANES data to examine adults (≥20 years) with cardiovascular-kidney-metabolic risk profiles. The circadian alignment evaluates the circadian light-activity synchronization through phasor analysis, which includes the assessment of phasor magnitude and acrophase. These parameters are subsequently categorized into quintiles for further study. Cross-sectional and longitudinal models were implemented to evaluate associations with CKM risk and adverse outcomes.

RESULTS 7,493 participants, representing 152,571,804 US adults (median 6.83-year follow-up). Participants with the shortest magnitude, characterized by the least overlap between light and activity cycles, not only have the highest risk of CKM (odds ratio [OR] 1.61, 95% CI 1.19–2.16) but also showed high all-cause mortality ([aHR] 1.84, 95% CI 1.37–2.47) and cardiovascular mortality (SHR 2.10, 95%CI 1.31–3.36). We observed a potential linear negative correlation between continuous phasor magnitude and the risk of CKM, as well as adverse outcomes (P-overall <0.001). Similar correlations were found in CVD, CKD, and DM separately. Males and older adults had elevated CKM incidence and all-cause/cardiovascular mortality versus female/younger counterparts. However, there was no statistical significance between phasor acorphase and CKM risk and adverse outcomes.

CONCLUSION Individuals with lower phasor magnitude, characterized by the least overlap between light and activity cycles, tend to have higher risks for CKM syndrome and adverse outcomes. These findings underscore quantifying circadian as a modifiable target for CKM primary prevention.

The authors have declared no competing interest.

This study was supported by the National Natural Science Foundation of China (No.82200500) and (No.82400407).

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Data in the present investigation was retrieved from the National Health and Nutrition Examination Survey (NHANES), which is a national, serial, one-time probability sampling design program to track health and nutrition patterns across age groups.The webste is:https://wwwn.cdc.gov/nchs/nhanes/default.aspx

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↵† Denotes joint first author

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