Admission ferritin in STEMI predicts long-term major adverse cardiovascular outcomes

Inflammation is known to be involved in atherosclerosis pathophysiology, plaque destabilization and acute coronary syndromes (ACS). Even though there have been several studies evaluating the prognostic value of inflammatory markers, there are only a handful of studies evaluating the role of ferritin. Serum ferritin, though commonly used as an indicator of iron status, is also known to be elevated in response to inflammation.

The purpose of this study is to investigate the value of ferritin in predicting long-term incidence of major adverse cardiovascular events (MACE) in patients with STEMI.

This is a substudy from the PHASE-MX registry. Briefly, PHASE-MX is a prospective cohort of patients with diagnosis of STEMI at our institution from 2018 to 2021. Patients were included if they were >18 years old, had a diagnosis of STEMI and had a ferritin determination on admission. The primary outcome of this study was to evaluate the correlation between initial serum ferritin level of ≥300 ng/mL and the incidence of MACE (composite of all-cause death, cardiogenic shock, recurrent myocardial infarction and new congestive heart failure [CHF]).

We included a total of 477 patients. Follow-up was maintained up to 4.5 years with a median of 1.1 years. Median time for ferritin evaluation from admission was 1 day (IQR 0-2 days). Ferritin value ≥300 ng/mL was found in 29.9% of patients. Mean age was 77 years, patients showed a prevalence of 45.4% for hypertension, 34.9% for diabetes and 19.7% for dyslipidemia. No differences in baseline characteristics were found among groups. The risk of the primary composite endpoint was statistically higher in those with a ferritin ≥300 ng/mL (HR 1.43, 95% CI 1.06 to 1.94, p=0.01). (Figure 1) Among individual endpoints, ferritin elevation was associated with all-cause death (HR 2.0, 95% CI 1.09 to 3.69) and new CHF (HR 1.46, 95% CI 1.05 to 2.04). This effect was maintained after adjustment for other inflammatory variables and GRACE score (HR 1.48, 95% CI 1.04 to 2.1, p=0.02). Across the full spectrum of ferritin (Figure 2), a very low value of <110 ng/mL marked the inflection point between protection and hazard for MACE (HR 1.02, 95% CI 0.99 to 1.04), however, iron deficiency did not have a protective effect (HR 0.93, 95% CI 0.69 to 1.26, p=0.67). A value of 299 ng/mL provided the initial point for hazard (HR 1.17, 95% CI 1.00 to 1.35, p=0.03).