Neutrophil-to-high-density lipoprotein cholesterol ratio and prevalent cardiometabolic multimorbidity in older adults: an exploratory cross-sectional analysis

The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), a composite surrogate marker derived from neutrophil count and HDL-C, has been reported to be associated with various metabolic and cardiovascular diseases. This study aimed to investigate the association between NHR and cardiometabolic multimorbidity (CMM) in older adults and to explore whether insulin resistance and uric acid metabolism may statistically account for part of this association. This study was based on data from the National Health and Nutrition Examination Survey (NHANES) and included a total of 5,987 older adults. CMM was defined as the coexistence of at least two cardiometabolic diseases within the same individual, including diabetes mellitus, coronary heart disease, and stroke. Weighted logistic regression, restricted cubic splines (RCS), subgroup analyses, and exploratory mediation analyses were performed to assess the association between NHR and CMM. Receiver operating characteristic (ROC) curves were used to evaluate the discriminatory ability of NHR for CMM. Multivariable weighted logistic regression analysis demonstrated that, compared with older adults in the lowest quartile (Q1) of NHR, those in the highest quartile (Q4) had 2.33-fold higher odds of CMM (95% CI: 1.56-3.48, P for trend < 0.001). Exploratory mediation analysis suggested that TyG, as a surrogate marker of insulin resistance, and uric acid statistically accounted for 23.78% (95% CI 16.08%-54.60%) and 13.69% (95% CI 9.31%-56.83%) of the NHR–CMM association, respectively. However, given the cross-sectional nature of the present study, these findings should not be interpreted as evidence of temporal or causal mediation. Moreover, RCS analysis revealed a nonlinear relationship between NHR and CMM risk (P for non-linearity < 0.0001). ROC analysis showed that NHR had modest but statistically higher discriminatory ability for CMM than the comparison indices. Our findings indicate that NHR is closely and positively associated with the CMM prevalence in the elderly population. The mediation patterns were consistent with the potential involvement of insulin resistance and uric acid–related metabolic-inflammatory pathways. However, because direct inflammatory mediators were not measured and the study was cross-sectional, these findings should be interpreted as association-based and hypothesis-generating rather than evidence of causal inflammatory mediation. Not applicable.