The Framingham steatosis index as a predictor of advanced CKM syndrome in US adults: Evidence from NHANES 2001 to 2018

The coexistence of cardiovascular disease (CVD), chronic kidney disease, and metabolic abnormalities represents the multifaceted cardiovascular-kidney -metabolic (CKM) syndrome, posing significant challenges for clinical management and public health. Emerging evidence implicates hepatic steatosis as a pivotal factor exacerbating metabolic imbalance, yet its precise contribution to CKM syndrome onset and progression remains insufficiently elucidated. Understanding this relationship is critical for refining disease stratification and therapeutic strategies. Utilizing a nationally representative sample of 20,595 adults aged 20 years and older from 9 cycles (2001-2018) of the National Health and Nutrition Examination Survey, this study employed the Framingham Steatosis Index (FSI) as a validated proxy for hepatic fat accumulation. CKM syndrome was categorized according to established diagnostic frameworks integrating cardiovascular, renal, and metabolic risk markers. Associations between FSI and advanced stages of CKM syndrome were examined through multivariable logistic regression analyses, with further exploration of potential effect modification by age, smoking status, and other demographic variables via subgroup and nonlinear modeling approaches. Incremental elevations in FSI corresponded to a significant increase in the odds of advanced CKM syndrome (adjusted OR 1.12; 95% CI: 1.08-1.17 per unit increase). Participants within the highest FSI quartile exhibited a 55% greater risk relative to those in the lowest quartile (OR 1.55; 95% CI: 1.27-1.90). The prevalence of advanced CKM syndrome in the study population was 18.82%. Interaction analyses highlighted that these associations were particularly pronounced among individuals younger than 60 years and among current smokers, suggesting differential susceptibility across populations. Moreover, the relationship between FSI and advanced CKM syndrome displayed a nonlinear pattern in older adults (≥60 years), indicative of complex age-dependent pathophysiological mechanisms. This study establishes hepatic steatosis, as approximated by FSI, as a significant independent marker of advanced CKM syndrome risk in U.S. adults. Incorporation of FSI into clinical assessments may improve early risk stratification and enable comprehensive, targeted interventions to reduce cardiovascular, renal, and metabolic morbidity. These findings underscore hepatic steatosis as a critical component in the multisystem pathogenesis of CKM syndrome.