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. 2024 Aug 17;23(1):305.
doi: 10.1186/s12933-024-02377-x.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

Alessandro Mantovani  1 , Fabiana Busti  2 , Nicolò Borella  1 , Enrico Scoccia  1 , Barbara Pecoraro  1 , Elena Sani  1 , Riccardo Morandin  1 , Alessandro Csermely  1 , Daniele Piasentin  1 , Elisabetta Grespan  1 , Annalisa Castagna  2 , Josh Bilson  3   4 , Christopher D Byrne  3   4 , Luca Valenti  5   6 , Domenico Girelli  2 , Giovanni Targher  7   8
Affiliations

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

Alessandro Mantovani et al. Cardiovasc Diabetol. .

Abstract

Background: The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.

Methods: We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).

Results: 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50-1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37-10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27-4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27-5.03; p = 0.008).

Conclusions: In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Keywords: Cardiovascular events; Ferritin; Hepcidin; Mortality; Type 2 diabetes.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Distribution of baseline plasma hepcidin concentrations, including the tertile cut points (marked with red and green dotted lines), among the study participants
Fig. 2
Fig. 2
Kaplan-Meier survival estimates (with 95% confidence intervals, as shaded areas) of the risk of developing the primary composite outcome over the follow-up period in patients with T2DM stratified by baseline plasma hepcidin tertiles (3rd tertile vs. 1st and 2nd tertiles combined)
See this image and copyright information in PMC

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