Association Between Sleep and Cardiovascular-Kidney-Metabolic Syndrome: Mediation Analysis of Inflammatory Biomarkers

Sleep disturbances are linked to individual cardiometabolic diseases, but their association with the emerging cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of interrelated conditions, remains less clear. To evaluate the association of sleep factors (sleep duration, diagnosed sleep disorder, self-reported trouble sleeping) with the risk of CKM syndrome.

We included 11,949 adults from the National Health and Nutrition Examination Survey (NHANES). A composite sleep score (0-3, from healthy to poor) was derived from sleep duration, diagnosed sleep disorder, and self-reported trouble sleeping. CKM syndrome was defined and staged (Stage 0-4) based on the coexistence and severity of cardiometabolic and kidney diseases. Systemic inflammation was assessed using the systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI). A poor sleep pattern was significantly associated with higher odds of CKM syndrome (fully adjusted odds ratio [OR] = 1.64, 95% confidence interval (CI): 1.37-1.95) and with more advanced CKM stages in an ordinal model, indicating a dose-response relationship. In exploratory mediation analysis, SII and SIRI appeared to partially mediate the association between self-reported trouble sleeping and CKM syndrome in initial models. However, this mediating effect was substantially attenuated and became nonsignificant for SII after comprehensive adjustment for adiposity (body mass index (BMI) and waist circumference) and lifestyle factors.

Poor sleep patterns are robustly associated with an increased risk and severity of CKM syndrome. While systemic inflammation was correlated with both sleep disturbances and CKM, its role as an independent mediator was largely explained by shared variance with obesity and metabolic factors. These findings underscore sleep health as a potential target for multimodal risk reduction within the CKM framework, though causality needs confirmation in longitudinal studies.