The association of ferritin with subclinical coronary artery calcification is an expression of underlying cardiometabolic risk

Introduction Observations of an association of hyperferritinemia (HF) and coronary artery calcification (CAC) have revealed conflicting results in the past. We therefore aimed to analyze the impact of HF on the risk of subclinical CAC in a population-based, Central-European cohort emphasizing cardiometabolic risk factors and genetic predisposition through a polygenic risk score (PRS). Material and Methods A subset of 1516 individuals of the Paracelsus 10.000 cohort was analyzed. HF was defined with SF>200 ng/ml for women and>300 ng/ml for men. The association with subclinical CAC was assessed univariate and using multiple regression models adjusted for sex, age, metabolic syndrome (MetS), SCORE2 and PRS and compared to a model for MetS with similar adjustments. Results Among the cohort, 12% (n=182) had HF. Univariate analysis showed a significant association between CAC and HF adjusted for sex and age (IRR: 1.0003, 95% CI: 1.0000–1.0006, p=0.028), sex and age combined with PRS (IRR: 1.0003, 95% CI: 1.000-1.004, p=0.044), SCORE2 (IRR: 1.0006, 95% CI: 1.0002–1.0009, p=0.001) and SCORE2 combined with PRS (IRR: 1.0006, 95% CI: 1.0003–1.0009, p=0.000). The association was abolished after adjustment for MetS (IRR: 1.0001, 95% CI: 0.9999–1.0005, p=0.366) and MetS combined with PRS (IRR: 1.0001, 95% CI: 0.9998–1.0005, p=0.262). A comparison of the models of HF or MetS with CAC revealed a better fit for the MetS model. Conclusion The risk of CAC associated with HF is likely attributable to underlying metabolic disease rather than HF independently. Publication History Article published online: 13 May 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany