Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population

Background: The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear. Purpose: To better understand this relationship, we explored the association of TSAT ratio (serum iron/total iron binding capacity) with mortality in the general population. Methods: The relationships of TSAT ratio with total and cardiovascular mortality were explored in 15 823 subjects age 20 and older from the Third National Health and Nutrition Examination Survey (1988–94). All subjects had vital status assessed through to 2006. Results: During follow-up, 9.7% died of which 4.4% were from cardiovascular disease. In unadjusted analysis, increasing TSAT ratio was inversely associated with mortality. With adjustment for baseline demographic and clinical characteristics, the TSAT–mortality relationship followed a j-shaped pattern. Compared with the referent group [ratio 23.7–31.3%: hazard ratio (HR) =1.00], subjects in the lowest two quartiles, <17.5 % and 17.5–23.7 %, experienced significantly higher mortality risks of 1.45 (1.19–1.77) and 1.27 (1.06–1.53), respectively, whereas subjects in the highest quartile, >31.3 %, experienced significantly higher mortality risks of 1.23 (1.01–1.49). The pattern of association was more pronounced for cardiovascular mortality with significantly higher mortality risks for the lowest two quartiles [HR = 2.09 (1.43–3.05) and 1.90 (1.33–2.72), respectively] and highest quartile HR = 1.59 (1.05–2.40). Conclusions: Both low and high TSAT ratios are significantly and independently associated with increased total and cardiovascular mortality. The optimal TSAT ratio associated with the greatest survival is between 24% and 40%.