Background: Ferritin constitutes a sensitive iron-storage index and multi-functional protein. Evidence on its association with mortality in general population is scarce and conflicting. We investigated the sex-specific associations of ferritin levels with all-cause and cardiovascular mortality in a population-based cohort.
Methods: Data came from the English Longitudinal Study of Ageing and the national mortality registry. The sample comprised 5,471 participants aged ≥52 years. Blood concentration of ferritin was measured at baseline in 2004-05. Sex-specific Cox proportional hazards models were estimated with adjustment for age, major chronic diseases, marital status, educational attainment, total net household wealth, anemia, inflammatory markers, body mass index, smoking, and physical activity. Stratified analyses by chronic disease status were also performed.
Results: We categorized ferritin in sex-specific quartiles. In men, we used, the following categorization: lowest (2-69ng/ml), second lowest (70-118ng/ml), second highest (reference category) (119-193ng/ml) and highest (194-598ng/ml) ferritin quartiles. In women, ferritin was categorized as follows: lowest (2-44ng/ml), second lowest (45-73ng/ml), second highest (reference category) (74-115ng/ml) and highest (116-341ng/ml) ferritin quartiles. 841 deaths of which 262 cardiovascular disease-related were recorded over a mean follow-up time of 7.7 years. Risk for all-cause mortality was found increased in men with hyperferritinemia (194-598ng/ml) and no history of major chronic diseases compared with the reference group [fully-adjusted HR: 1.49 (95%CI 1.03-2.16)]. Among women, those in the lowest ferritin quartile (2-44ng/ml) had increased risk for all-cause mortality [fully-adjusted HR: 1.59 (95%CI 1.18-2.13)] compared with the reference group after adjustment for all covariates. Regarding cardiovascular mortality, we observed a positive association with ferritin levels in men, which was blunted after adjustment for inflammatory markers and lifestyle parameters. Men with no major chronic diseases who were in the highest ferritin quartile had a significantly increased risk of cardiovascular mortality. No association between ferritin levels and cardiovascular mortality was detected in women.
Conclusion: Circulating ferritin levels showed sex-specific prognostic patterns. High ferritin levels in men with no major chronic disease and low ferritin levels in all women were associated with increased all-cause mortality after adjusting for covariates. High ferritin levels in men with no major chronic diseases were also independently associated with an increased risk of cardiovascular mortality. Future research is needed to clarify the prognostic role of ferritin.