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

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

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.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers* / blood
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / mortality
  • Cause of Death
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / mortality
  • Female
  • Ferritins / blood
  • Hepcidins* / blood
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Up-Regulation*

Substances

  • Hepcidins
  • Biomarkers
  • Ferritins
  • HAMP protein, human