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Published on: September 27, 2024
Iron Metabolism, Hepcidin, and Mortality (the Ludwigshafen Risk and Cardiovascular Health Study)
Tanja B Grammer1,2, Hubert Scharnagl3, Alexander Dressel4
1Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Tanja.Grammer@medma.uni-heidelberg.de.
Insights
Iron metabolism markers like ferritin and transferrin saturation show a J-shaped link to mortality in stable coronary artery disease (CAD) patients. Hepcidin levels inversely correlate with mortality risk.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biochemistry
Background:
- Anemia is a known risk factor for coronary artery disease (CAD) and mortality.
- The specific role of iron metabolism in cardiovascular outcomes remains unclear.
Purpose of the Study:
- To investigate the association between iron metabolism markers and mortality in patients undergoing coronary angiography.
- To clarify the relationship between iron status and cardiovascular death in stable CAD patients.
Main Methods:
- Analysis of iron metabolism (serum iron, transferrin saturation, ferritin, soluble transferrin receptor [sTfR], hemoglobin, hepcidin) in 1480 stable CAD patients and 682 controls.
- Median follow-up of 9.9 years to assess cardiovascular death and total mortality.
- Multivariate-adjusted hazard ratios (HRs) were calculated comparing lowest and highest quartiles to reference quartiles, accounting for J-shaped associations.
Main Results:
- Serum iron, transferrin saturation, ferritin, and sTfR exhibited J-shaped associations with total mortality.
- Highest quartiles of iron, transferrin saturation, and sTfR were linked to increased total mortality (HRs 1.44, 1.37, 1.76, respectively).
- Elevated hepcidin (highest quartile) was associated with significantly lower total mortality (HR 0.62) and cardiovascular death (HR 0.70).
Conclusions:
- Iron status markers (serum iron, transferrin saturation, ferritin, sTfR) show complex, J-shaped associations with mortality in stable CAD patients.
- Hemoglobin had only a marginal association with mortality.
- Hepcidin demonstrates a continuous inverse relationship with mortality, suggesting a protective role.
Background:
Anemia has been shown to be a risk factor for coronary artery disease (CAD) and mortality, whereas the role of iron metabolism remains controversial.
Methods:
We analyzed iron metabolism and its associations with cardiovascular death and total mortality in patients undergoing coronary angiography with a median follow-up of 9.9 years. Hemoglobin and iron status were determined in 1480 patients with stable CAD and in 682 individuals in whom significant CAD had been excluded by angiography.
Results:
Multivariate-adjusted hazard ratios (HRs) for total mortality in the lowest quartiles of iron, transferrin saturation, ferritin, soluble transferrin receptor (sTfR), and hemoglobin were 1.22 (95% CI, 0.96-1.60), 1.23 (95% CI, 0.97-1.56), 1.27 (95% CI, 1.02-1.58), 1.26 (95% CI, 0.97-1.65), and 0.99 (95% CI, 0.79-1.24), respectively, compared to the second or third quartile, which served as reference (1.00) because of a J-shaped association. The corresponding HRs for total mortality in the highest quartiles were 1.44 (95% CI, 1.10-1.87), 1.37 (95% CI, 1.05-1.77), 1.17 (95% CI, 0.92-1.50), 1.76 (95% CI, 1.39-2.22), and 0.83 (95% CI, 0.63-1.09). HRs for cardiovascular death were similar. For hepcidin, the adjusted HRs for total mortality and cardiovascular deaths were 0.62 (95% CI, 0.49-0.78) and 0.70 (95% CI, 0.52-0.90) in the highest quartile compared to the lowest one.
Conclusions:
In stable patients undergoing angiography, serum iron, transferrin saturation, sTfR, and ferritin had J-shaped associations and hemoglobin only a marginal association with cardiovascular and total mortality. Hepcidin was continuously and inversely related to mortality.
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