Plasma metallomics reveals potential biomarkers and insights into the ambivalent associations of elements with acute myocardial infarction

Abstract

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Using a validated and efficient ICP-MS/MS-based workflow, a total of 30 metallomic features were profiled in a study comprising 101 AMI patients and 66 age-matched healthy controls. The metallomic features include 12 essential elements (Ca, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, Zn), 8 non-essential/toxic elements (Al, As, Ba, Cd, Cr, Ni, Rb, Sr, U, V), and 10 clinically relevant element-pair product/ratios (Ca/Mg, CaxP, Cu/Se, Cu/Zn, Fe/Cu, P/Mg, Na/K, Zn/Se). Preliminary linear regression with feature selection confirmed smoking status as a predominant determinant for the non-essential/toxic elements, and revealed potential routes of action. Univariate assessments with adjustments for covariates revealed insights into the ambivalent relationships of Cu, Fe, and P with AMI, while also confirming cardioprotective associations of Se. Also, beyond their roles as risk factors, Cu and Se may be involved in the response mechanism in AMI onset/intervention, as demonstrated via longitudinal data analysis with 2 additional time-points (1-/6-month follow-up). Finally, based on both univariate tests and multivariate classification modelling, potentially more sensitive markers measured as element-pair ratios were identified (e.g., Cu/Se, Fe/Cu). Overall, metallomics-based biomarkers may have utility for AMI prediction.