The association of biomarkers of iron status with mortality in US adults

Background and Aims: Elevated iron biomarkers are associated with diabetes and other cardiometabolic abnormalities in the general population. It is unclear whether they are associated with an increased risk of all-cause or cause-specific mortality. The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. Methods and Results: A prospective cohort study was conducted with 12,258 adults participating in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population. Study participants were recruited in 1988-1994 and followed through December 31, 2006 for all-cause, cardiovascular disease, and cancer mortality. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause mortality comparing the fourth versus the second quartiles of ferritin and transferrin saturation were 1.09 (0.82-1.44; p-trend across quartiles = 0.92) and 1.08 (0.82-1.43; p-trend across quartiles = 0.62), respectively, for men, 1.43 (0.63-3.23; p-trend across quartiles = 0.31) and 1.48 (0.70-3.11; p-trend across quartiles = 0.60), respectively, for premenopausal women, and 1.03 (0.79-1.34; p-trend across quartiles = 0.95) and 1.17 (0.92-1.49; p-trend across quartiles = 0.63), respectively, for postmenopausal women. Quartile of ferritin and transferrin saturation also showed no association between biomarkers of iron status and mortality. Conclusions: In a large nationally representative sample of US adults, within the spectrum of normal iron metabolism, ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer.