Elevated serum transferrin saturation and mortality.

BACKGROUND: A large proportion of US adults have elevated transferrin saturation, an indicator of a predisposition for iron overload. The purpose of this study was to evaluate the relationship between elevated serum transferrin saturation and mortality.
METHODS: This cohort study was conducted using data from the First Health and Nutrition Examination Survey 1 (1971-1974) (NHANES I) merged with the NHANES I Epidemiologic Followup Study (1992) (N = 10,714). We used SUDAAN and appropriate weights to make population estimates for the adult US population (aged 25 to 74 years at baseline). All-cause mortality was evaluated in relation to serum transferrin saturation of greater than 45%, greater than 50%, greater than 55%, and greater than 60% using Cox proportional hazards regression.
RESULTS: In a Cox proportional hazards model controlling for potential confounders, including comorbid diseases, smoking, and cholesterol, all-cause mortality is significantly greater for persons with a serum transferrin saturation of more than 55%, compared with those with saturations below this cutoff (hazards ratio [HR] = 1.60, 95% confidence interval [CI], 1.17-2.21). No one who died had hemochromatosis as any of the 20 listed causes of death. Many of the underlying causes of death for persons with serum transferrin saturation levels of more than 55% are common causes of death in the general population, although these persons were more likely to have died of cirrhosis and diabetes, a finding consistent with iron overload.
CONCLUSIONS: In this nationally representative cohort of adults, those with elevated serum transferrin saturation, more than 2% of the adult US population, were at increased risk for all-cause mortality.