Total mortality by transferrin saturation levels: two general population studies and a metaanalysis

Area of Science:

• Cardiovascular Science
• Hematology
• Epidemiology

Background:

• Hereditary hemochromatosis is associated with increased mortality.
• The link between elevated transferrin saturation (TS) and mortality in the general population remains unclear.

Purpose of the Study:

• To investigate the association between baseline transferrin saturation (TS) and all-cause mortality in the general population.
• To determine if elevated TS, as a proxy for iron overload, predicts increased mortality risk.

Main Methods:

• Analysis of mortality data from two Danish population-based studies (Copenhagen General Population Study and Copenhagen City Heart Study).
• Inclusion of 45,159 individuals with up to 18 years of follow-up.
• Meta-analysis combining these studies with an additional general population study.

Main Results:

• Reduced cumulative survival observed in individuals with TS ≥ 50% compared to those with TS < 50% (P < 0.0001).
• Multifactorially adjusted hazard ratios for total mortality were 1.4 overall (P < 0.001), 1.3 in men (P = 0.003), and 1.5 in women (P = 0.005) for TS ≥ 50% vs < 50%.
• A stepwise increase in mortality risk was associated with increasing TS levels, with TS ≥ 80% showing the highest risk (HR 2.2, P < 0.001).

Conclusions:

• Individuals in the general population with TS ≥ 50% face an elevated risk of premature death.
• Elevated transferrin saturation is a significant predictor of mortality, independent of clinically overt hereditary hemochromatosis.