Association between system immune-inflammation index and the risk of all-cause, cancer, and non-cancer mortality in the general population: Results from National Health and Nutrition Examination Survey 2005-2018

Abstract Background Cancer is a major global public health issue and the second leading cause of death globally following cardiovascular disease. Inflammation plays an essential role in the progression of cancer. The system immune-inflammation index (SII) was recognized as an accurate biomarker reflecting immunoinflammatory status. This study aimed to identify the association between SII with all-cause, cancer and non-cancer mortality among general population in the United States.Methods 25,955 participants (≥ 18 years) were included from 2005–2018 National Health and Nutrition Examination Survey (NHANES) and were divided into four groups according to the SII quartiles. Weighted multivariate Cox regression was used to assess the correlation between SII and mortality. Subgroup analyses were conducted to identify the effects of other covariates on the relationship between SII and mortality. A restricted cubic spline (RCS) model was subsequently used to explore the dose-response relationship between SII and mortality. Survival analysis was assessed using Kaplan-Meier method.Results In fully adjusted model, the adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) of individuals in Q4, which indicated the highest immunoinflammatory level, were 1.24 (1.09, 1.41) for all-cause mortality and 1.41 (1.23, 1.63) for non-cancer mortality compared with Q1. Besides, the aHR and 95% CIs in Q2 of SII were 0.70 (0.50, 0.99) and in Q3 were 0.68 (0.52, 0.87) compared with Q1 for cancer mortality. In RCS analysis, non-linear relationships of J-shaped curves were observed in the association between SII with all-cause and non-cancer mortality. Additionally, a U-shaped curve was identified between SII and cancer mortality with a threshold value of 445.22.Conclusion Our findings imply that SII can serve as a potential prognosis indicator among general population. Elevated SII is associated with higher all-cause and non-cancer mortality. Besides, both lower and higher SII can serve as predictive factors for cancer mortality.