Association of neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-monocyte-to-lymphocyte ratio (NMLR) with mortality in adults with osteoarthritis: Evidence from NHANES 2001 to 2018

The prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-monocyte-to-lymphocyte ratio (NMLR) in osteoarthritis (OA) remains unclear. This study aimed to explore the association between biomarkers and clinical outcomes in OA patients. Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2001 to 2018 were used in this study. Kaplan-Meier survival analysis, multivariable Cox hazard regression analysis, and restricted cubic spline (RCS) were used to assess mortality associations and nonlinear relationships. Subgroup and sensitivity analyses were performed to ensure the robustness and reliability. A total of 578 all-cause deaths and 190 cardiovascular deaths were recorded. The Kaplan-Meier analyses indicated reduced survival among individuals with the highest NLR and NMLR levels. Multivariable Cox regression analysis showed that elevated NLR was associated with higher all-cause mortality (HR = 1.17, 95% CI: 1.08-1.25; P < .001) and approached statistical significance for increased cardiovascular mortality (HR = 1.14, 95% CI: 0.99-1.29; P = .053). Elevated NMLR was significantly associated with higher all-cause mortality (HR = 1.16, 95% CI: 1.08-1.24; P < .001) and cardiovascular mortality (HR = 1.13, 95% CI: 1.01-1.28; P = .041). The RCS model indicated that NLR was nonlinearly associated with all-cause and cardiovascular mortality, with an inflection point at 2.04 for both outcomes. The NMLR was nonlinearly associated with all-cause and cardiovascular mortality, with an inflection point at 2.32 for both outcomes. Subgroup analyses showed the association between NLR/NMLR and all-cause mortality was more significant in individuals aged ≥ 60 years (P for interaction < .05). NLR and NMLR are associated with an elevated risk of all-cause and cardiovascular mortality in OA individuals. Both biomarkers may serve as useful indicators for assessing inflammatory burden and offer promising clinical prospects for risk stratification and disease management.