Effect of iron status on myocardial infarction: A two-sample Mendelian randomization study

Background: In observational studies, connections have been identified between iron status and myocardial infarction (MI). The significance of changes in iron status as either a risk factor or a result of MI remains unclear.

Methods: We obtained our instrumental variables from a meta-analysis of three GWASs in Iceland, the UK, and Denmark, which discovered 62 independent sequence variants across 56 loci linked to blood iron levels, ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT), and the Genetics of Iron Status (GIS) database for transferrin. To evaluate the connection between iron status markers and myocardial infarction (MI), we used three GWAS datasets focused on MI outcomes. The chosen datasets included one representing the European population (ebi-a-GCST011364: n case = 14,825, n control = 380,970; finn-b-I9_MI: n case = 12,801, n control = 187,840) and another with a mixed population (ieu-a-798: n case = 43,676, n control = 128,199). The primary method used in our study was inverse variance-weighting, while we also assessed heterogeneity and horizontal pleiotropy to enhance the robustness of our findings.

Results: The main analysis with the inverse variance-weighted method showed no significant impact of iron marker levels on MI risk in the ebi-a-GCST011364 and finn-b-I9-MI cohorts. In contrast, the ieu-a-798 cohort indicated that higher ferritin levels had a protective effect against MI (OR = 0.87, 95 % CI 0.78-0.98, P = 0.03). Additionally, TSAT showed an association with decreased MI risk (OR = 0.91, 95 % CI 0.84-0.98, P = 0.01). No significant correlations were observed for other iron status traits examined in this study. Evaluations of horizontal pleiotropy and heterogeneity showed no abnormalities, further strengthening the reliability of our results.

Conclusions: Our multi-cohort MR analysis suggests a potential protective effect of higher ferritin levels and TSAT against MI risk. These findings contribute to our understanding of the relationship between iron status markers and cardiovascular health, offering insights for future research and potential therapeutic interventions.