Fig. 3: Prospective association of inflammatory markers with physical frailty and depression incidence.

A All nine inflammatory markers showed significant associations with physical frailty while controlling for several covariates. Analysis employed linear mixed-effects models, which tested the statistical significance of coefficients against a t-distribution. Size of the bar and the internal center represent mean Cohen’s d. The error bar represents the corresponding 95% CI. B Serum CRP showed the strongest association with physical frailty (n = 352,277). Boxplot elements were defined as follows: the center line is the median value; box limits are the upper and lower quartiles; whiskers are 1.5× the interquartile range. C Cox proportional hazards models provided evidence of linear associations between eight of the nine inflammatory markers (except monocyte percentage) and incident depression (Z-tests). Dots: mean HRs; Horizontal lines: 95% CI. D The exposure-response curve between inflammatory markers and risk of depression incidence. Significant non-linear associations were only observed for leukocytes, platelets, and neutrophils. Similar patterns of associations were observed by investigating the tertiles of each inflammatory maker (barplot in each panel). All P values were two-sided, and unadjusted. Size of the bar and the internal center represent mean HRs. The error bar and shadow indicate the corresponding 95% CI. E Eight out of the nine inflammatory markers significantly mediated the prospective association between physical frailty and depression incidence while adjusting for covariates and multiple comparisons. Path thickness indicates the strength of associations, and numerical values for the largest and smallest effect sizes are provided for reference. The number of participants with complete data for these inflammation markers were n = 342,268 (leukocyte), n = 342,771 (lymphocyte, neutrophil%, monocyte), n = 342,775 (lymphocyte%, monocyte%, neutrophil%), n = 343,371 (platelet), and n = 352,277 (CRP). Two-sided unadjusted P values and HRs were derived from Cox proportional hazard model (Z-tests). CRP, C-reactive protein. HR hazard ratio. Icons were made from https://www.svgrepo.com/. Source data are provided as a Source Data file.