Abstract
The systemic immune-inflammation index (SII) is widely used in monitoring disease progression, evaluating treatment efficacy, and predicting outcomes across diverse diseases. Yet, its roles in iron deficiency (ID) remains unclear. This investigation aims to explore the association between SII and ID in 20-80 years old individuals which can accurately represent the people's health status in the United States. This cross-sectional study analyzed data from 4,075 National Health and Nutrition Examination Survey(NHANES) participants. The relationship between SII (SII = platelet counts × neutrophil counts/ lymphocyte counts) and C-reactive protein (CRP) with iron metabolism indicators including total body iron (TBI), serum ferritin (SF), soluble transferrin receptor (sTfR), total iron binding capacity (TIBC), transferrin saturation (TS), mean corpuscular volume (MCV), and hemoglobin (Hb) and ID, anemia and iron deficiency anemia (IDA) were assessed using multiple linear regression or logistic regression, respectively. Interaction tests were performed to explore whether these relationships between SII and iron metabolism indicators varied by sex, age, and race. Among 9,254 screened participants, 4,075 U.S. adults aged 20-80 years met inclusion criteria. Compared to individuals with low SII, high SII people have lower family income-to poverty ratio (PIR), higher proportion of females, lower level of SF, TBI, TS and Hb, higher level of sTfR, TIBC and the odd of ID and IDA. In the fully adjusted model, SII exhibited significant correlations with sTfR (β = 0.62, 95% CI 0.45－0.78), TIBC (β = 13.19, 95% CI 8.90－17.49), SF (β = -16.07, 95% CI -30.51－-1.64), TBI (β = -1.23, 95% CI -1.56 － -0.90), TS (β = -1.55, 95% CI -2.53－-0.57), Hb (β = -0.18, 95% CI -0.30－-0.05), ID (OR = 2.22, 95% CI 1.69－2.85) and IDA (OR = 1.96, 95% CI 1.35－2.85) and CRP exhibited significant correlations with SII (β = 010.62, 95% CI 9.55－11.70), sTfR (β = 0.02, 95% CI 0.01－0.03), SF (β = 1.62, 95% CI 1.05－2.19), TBI (β = 0.02, 95% CI 0.01－0.03). Smooth curves in all participants indicated correlations between SII and various iron indicators. Independent correlations between the SII and various iron markers, as well as the occurrence of ID and IDA, were observed in the interaction tests stratified by age, sex, and race. An association was identified between SII representing systemic inflammation and a tendency towards ID, along with heightened odds of experiencing both ID and IDA. SII exhibited a more comprehensive association with ID than CRP.