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%.