The association between cardiometabolic index and rheumatoid arthritis in American adults: the potential mediating role of hypertension, diabetes, and inflammatory markers

A bstract   Background: The cardiometabolic index (CMI) is a novel integrated measure of dyslipidemia (as reflected by the triglyceride to high-density lipoprotein cholesterol ratio) and central adiposity (as represented by the waist-to-height ratio). While CMI has been linked to various metabolic disorders, its association with rheumatoid arthritis (RA) remains unclear. This study aimed to examine the relationship between CMI and RA among U.S. adults and to investigate potential mediating pathways.   Methods: We analyzed data from 9,765 adults participating in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. Weighted multivariable logistic regression models were used to evaluate the association between CMI and RA. Nonlinearity was assessed using restricted cubic splines (RCS). Subgroup analyses were performed to test the robustness of the findings, and mediation analysis was conducted to quantify the contributions of hypertension, diabetes, and inflammatory markers.   Results:  In fully adjusted models, each unit increase in CMI was positively associated with RA risk (OR = 1.20, 95% CI: 1.08–1.33).. Participants in the highest CMI tertile had a 74% increased risk of RA compared to those in the lowest tertile (OR = 1.74, 95% CI: 1.33–2.28). RCS analysis identified a nonlinear relationship with a threshold effect at a CMI value of 1.63. Below this inflection point, the association was more pronounced (OR = 1.53, 95% CI: 1.27– 1.85). Exploratory mediation analyses showed that hypertension (explaining 22.2% of the total association) and diabetes (15.9%) statistically accounted for a significant proportion of the association, with neutrophil count also contributing modestly (5.4%).   Conclusion: Higher CMI is positively associated with RA prevalence among U.S. adults, with evidence of a threshold effect. This relationship may be largely statistically explained by metabolic comorbidities,, particularly hypertension and diabetes.