The neutrophil percentage-to-albumin ratio predicts all-cause and cardiovascular mortality among U.S. adults with rheumatoid arthritis: results from NHANES 1999-2010.

BACKGROUND: Rheumatoid arthritis (RA) is associated with systemic inflammation and an elevated risk of all-cause and cardiovascular mortality. The neutrophil percentage-to-albumin ratio (NPAR) is a novel composite biomarker integrating inflammatory and nutritional status, but its prognostic role in RA remains unknown.

METHODS: This study included 685 U.S. adults with RA from the National Health and Nutrition Examination Survey (NHANES) 1999-2010. NPAR was calculated as neutrophil percentage divided by serum albumin and categorized into tertiles (Q1: low, Q2: medium, Q3: high). All-cause and cardiovascular mortality were obtained via linkage to the National Death Index. Multivariable Cox proportional hazards models were used to assess the association between NPAR and mortality, with sequential adjustment for demographic, lifestyle, and clinical factors. In addition to NPAR, we also examined the individual components (neutrophil percentage, serum albumin) and C-reactive protein (CRP) for comparative analysis. Kaplan-Meier survival curves and restricted cubic splines (RCS) were used to visualize survival differences and dose-response relationships.

RESULTS: Over a median follow-up of 155.66 months, compared with Q1, the highest NPAR tertile (Q3) was independently associated with increased risks of all-cause mortality (fully adjusted hazard ratio [HR] = 1.87, 95% confidence interval [CI] 1.18-2.96, P = 0.008). Continuous NPAR was independently associated with increased risks of all-cause mortality (fully adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 1.08-1.24, P < 0.001) and cardiovascular mortality (HR = 1.23, 95% CI 1.06-1.42, P = 0.005). In comparative analyses, serum albumin also showed a strong inverse association with all-cause mortality (all-cause: HR = 0.26, 95% CI 0.15-0.47, P < 0.001), while neutrophil percentage and CRP demonstrated weaker or non-significant associations after full adjustment. Kaplan-Meier curves showed progressively lower survival across NPAR tertiles (log-rank P < 0.001). RCS analysis indicated a linear dose-response relationship between continuous NPAR and both mortality outcomes (all-cause: overall P < 0.001, nonlinear P = 0.090; cardiovascular: overall P = 0.002, nonlinear P = 0.290).

CONCLUSION: Elevated NPAR is an independent predictor of all-cause and cardiovascular mortality in patients with RA. Given its accessibility and low cost, NPAR may serve as a practical biomarker for risk stratification and prognostic assessment in RA management. Key Points • This study identifies the neutrophil percentage-to-albumin ratio (NPAR) as a novel, independent predictor of both all-cause and cardiovascular mortality in patients with rheumatoid arthritis. • The association between higher NPAR and increased mortality risk persists after rigorous adjustment for traditional risk factors, health behaviors, and clinical comorbidities, as well as mutual adjustment for C-reactive protein (CRP). • NPAR, calculated from routine complete blood count and metabolic panels, is a more comprehensive prognostic tool than its individual components (neutrophil percentage or albumin alone). • The findings suggest NPAR could be a practical and cost-effective biomarker for improving risk stratification and guiding more aggressive management in high-risk RA patients.