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

Abstract

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%.

Figure 1.

Association of TSAT ratio (%) in quartile groups with all-cause mortality in (a) men and (b) women. In (a), *P < 0.05, **P < 0.01 vs. referent quartile 23.7–31.3% (N = 7405); in (b), *P < 0.05 vs. referent quartile 23.7–31.3% (N = 8418). Adjusted for race, comorbid conditions, serum albumin, ferritin, haemoglobin level and poverty income ratio.

Figure 2.

Association of TSAT ratio (%) in decile groups with all-cause mortality. *P < 0.05, **P < 0.01 vs. referent quartile 23.7–31.3%. Multivariable model adjusted for age, sex, race, comorbid conditions, serum albumin, ferritin, haemoglobin level and poverty income ratio.