Association between complete blood count-derived inflammatory markers and the risk of frailty and mortality in middle-aged and older adults

Objective This study aimed to evaluate the association between six complete blood count (CBC)-derived inflammatory markers [neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV)] and the risk of frailty and mortality.Methods Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality was identified using the National Death Index until December 31, 2019. Multiple logistic regression analysis was conducted to evaluate the association between six CBC-derived inflammatory markers and frailty. The Cox regression model assessed the association between six CBC-derived inflammatory markers and mortality in frail populations. Restricted cubic spline (RCS) was used to visualize the association of the six CBC-derived inflammatory markers with mortality risk. The predictive value of CBC-derived inflammatory markers for mortality was further assessed using a random survival forest (RSF) approach.Results This study analyzed data from a total of 16,705 middle-aged and older participants. Among them, 6,503 participants were frail, with a mortality rate of 41.47%. Multiple logistic regression analysis showed that NLR, MLR, PLR, SII, SIRI, and PIV were positively associated with frailty risk. The Cox regression model revealed that participants in the highest quartile had a significantly increased risk of death compared to those in the lowest quartile: NLR (HR = 1.73, 95% CI:1.54, 1.94), MLR (HR = 1.71, 95% CI:1.51, 1.93), PLR (HR = 1.28, 95%CI: 1.15, 1.43), SII (HR = 1.50, 95%CI:1.34, 1.68), SIRI (HR = 1.88, CI 95%:1.67, 2.12), PIV (HR = 1.55, 95%CI:1.38, 1.73). Random survival forest (RSF) analyses demonstrated that MLR had the highest predictive value for mortality risk middle-aged and older adult frail participants.Conclusion The results suggest that CBC-derived inflammatory markers are associated with a higher risk of frailty as well as mortality in the middle and old-aged population of the United States.