Associations of inflammation-related hematological profile with the early-stages of cardiovascular-kidney-metabolic syndrome and the mediating role of body composition: evidence from the China National Health Survey

BACKGROUND: Chronic low-grade inflammation is increasingly recognized as a pivotal driver in the development of early-stage cardiovascular-kidney-metabolic (CKM) syndrome. Nonetheless, the complex interplay among inflammation-associated hematological indices, body composition, and CKM risk remains inadequately understood. METHODS: In this cross-sectional study, data from 5,692 participants of the China National Health Survey (CNHS) were analyzed. We employed advanced machine learning techniques-including Random Forest, Least Absolute Shrinkage and Selection Operator​(LASSO) regression, and eXtreme Gradient Boosting (XGBoost)-in conjunction with traditional epidemiological methods to assess the predictive value of an inflammation-related hematological profile for early-stage CKM. Restricted cubic spline regression was used to explore nonlinear dose-response relationships, and generalized structural equation modeling investigated the mediating role of body composition in the inflammation-CKM pathway. RESULTS: Six biomarkers-Neutrophil-to-HDL ratio (NHR), Monocyte-to-HDL ratio (MHR), High-sensitivity C-reactive protein/albumin ratio (CAR), High-fluorescence reticulocyte fraction (HFR), Reticulocyte production index (RPI), and Reticulocyte count (RET#)-were consistently prioritized across models. Participants in the highest quartiles of NHR, MHR, and RET# exhibited markedly elevated odds of early-stages of CKM (OR = 10.4, 7.75, and 6.99, respectively; all P for trend < 0.0001). Nonlinear analyses revealed critical thresholds-specifically, NHR > 7.05 and MHR > 0.66-beyond which early-stages of CKM risk escalated steeply. Mediation analyses indicated that imbalances in body composition, particularly increased adiposity and reduced muscle mass, accounted for 20-57% of the association between systemic inflammation and early-stage of CKM syndrome. Subgroup analyses further underscored that the predictive impact of reticulocyte parameters was amplified in smokers and individuals aged < 60 years. CONCLUSION: This study validates NHR and MHR as robust, clinically actionable biomarkers for early CKM screening. The delineated nonlinear thresholds and the mediating effects of body composition provide a strategic framework for targeted interventions-prioritizing anti-inflammatory treatments in high-risk groups (e.g., smokers with RET# >143.03 × 10³/µL) and muscle-preserving therapies to mitigate sarcopenic adiposity.