Serum ferritin/C-reactive protein ratio is a simple and effective biomarker for diagnosing iron deficiency in the context of systemic inflammation

Summary Background Diagnosing iron deficiency is challenging in the presence of systemic inflammation. Aim To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome. Design Test prospective cohort and validation retrospective cohort. Methods A prospective cohort of inpatients (n = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n = 795) further assessed the predictive power of this ratio. Results In a training cohort (median age 76 years [57–84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57–84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85–0.90], with an odds ratio of 37.9 [95% CI: 20.3–68.9] for the threshold of ≤6. Conclusion In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies.