Abstract
Purpose: Inflammation plays a central role in the occurrence and progression of cardiovascular disease (CVD). However, the intricate relationships between sleep patterns, inflammatory markers, and CVD risk remain insufficiently understood. This study aims to explore these associations, with a specific focus on the mediating role of inflammatory markers and their nonlinear effects. Methods: This study used a multiethnic adult population (N = 8752) from the National Health and Nutrition Examination Survey (NHANES) database (four data cycles from 2005-2006, 2007-2008, 2015-2016, and March 2017-2020). Multivariate logistic regression assessed the effects of sleep patterns and inflammatory markers on CVD risk. Furthermore, the mediating effects of the neutrophil-platelet ratio (NPR) and the systemic immune-inflammation index (SII) were assessed. Binary logistic regression was utilized to analyze the correlations between quartile groupings of inflammatory markers (SII and NPR) and CVD, as well as its specific types. The nonlinear relationship between inflammatory markers and CVD risk was explored using a generalized additive model (GAM). Results: Trouble sleep pattern significantly increased the risk of CVD (odds ratio [OR] = 2.7558, 95% confidence interval [CI]: 1.9019, 3.9931, p < 0.0001). Mediation analyses showed NPR mediated 17.38% and SII mediated 3.27% of the association. GAM showed that NPR (p-trend < 0.0001) and SII (p-trend = 0.001) had a significant inverted "U" shaped relationship with CVD risk, with higher inflammation increasing CVD risk up to a point, after which the risk decreased. Conclusion: Trouble sleep pattern significantly increased CVD risk, NPR and SII partially mediated the relationship between sleep patterns and CVD risk, and the nonlinear relationship with CVD risk suggests a bi-directional mechanism for the regulation of inflammatory markers. These findings offer new insights for inflammatory interventions and sleep health management in CVD prevention.