Correlation between CBC-derived inflammatory indicators and all-cause mortality with rheumatoid arthritis: a population-based study

Yu Liu; Yiping Liu; Shao Fan; Jing Yang; Mingxi Xu; Lin Zhao; Changyan Liu; Yida Xing; Xiaodan Kong

doi:10.3389/fmed.2025.1538710

Correlation between CBC-derived inflammatory indicators and all-cause mortality with rheumatoid arthritis: a population-based study

Front Med (Lausanne). 2025 Jun 10:12:1538710. doi: 10.3389/fmed.2025.1538710. eCollection 2025.

Authors

Yu Liu^#^{1

2}, Yiping Liu^#¹, Shao Fan³, Jing Yang^{1

2}, Mingxi Xu¹, Lin Zhao¹, Changyan Liu¹, Yida Xing¹, Xiaodan Kong¹

Affiliations

¹ Department of Rheumatology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
² Dalian Key Laboratory of Autoantibody Detection, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
³ College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

^# Contributed equally.

Abstract

Objectives: We investigated the relationship between inflammatory indicators derived from complete blood cell (CBC) counts and all-cause mortality in individuals with rheumatoid arthritis (RA).

Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2018, with a median follow-up duration of 78 months. The inflammatory indicators derived from CBC included several types: the systemic inflammatory response index (SIRI), the systemic immune-inflammation index (SII), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR). The multiple COX regression models were used to estimate adjusted hazard ratios (HRs) and 95% CIs concerning all-cause mortality of participants with RA, which focused on CBC-derived inflammatory indicators. Additionally, restricted cubic spline (RCS) curve was utilized to investigate non-linear associations.

Results: The research comprised a cohort of 1,314 individuals, among whom 246 with RA succumbed during a median follow-up duration of 78 months. After adjusting for key covariates, the mortality rate in patients with RA who had high SIRI, NLR, and MLR levels was considerably higher than in those with medium or low SIRI, NLR, and MLR levels. Compared with the lowest tertile, the highest tertiles of SIRI (HR 1.87, 95% CI: 1.12-3.13), NLR (HR 1.79, 95% CI: 1.10-2.92), and MLR (HR 1.88, 95% CI: 1.17-3.02) were associated with an increased risk of all-cause mortality. The Kaplan-Meier analysis indicated a significant decrease in the survival probability among individuals with elevated SIRI, NLR, and MLR levels. The RCS analysis revealed a linear association between SIRI, NLR, MLR, and RA-related all-cause mortality, whereas a non-linear relationship was identified between the SII, PLR, and mortality.

Conclusion: This investigation revealed that the SIRI, NLR, and MLR are novel, valuable, and convenient inflammatory indicators. In the United States adults with RA, higher SIRI, NLR, and MLR were independently associated with an increased long-term mortality risk. These findings not only assist in uncovering the potential utility of predicting RA outcomes but also provide rheumatologists valuable guidance for disease management.

Keywords: NHANES; monocyte-to-lymphocyte ratio; mortality; neutrophil-to-lymphocyte ratio; rheumatoid arthritis; systemic inflammatory response index.