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

Si Ying Lim; Hiranya Dayal; Song Jie Seah; Regina Pei Woon Tan; Zhi En Low; Anna Karen Carrasco Laserna; Sock Hwee Tan; Mark Y Chan; Sam Fong Yau Li

doi:10.1016/j.jtemb.2023.127148

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

J Trace Elem Med Biol. 2023 May:77:127148. doi: 10.1016/j.jtemb.2023.127148. Epub 2023 Mar 5.

Authors

Si Ying Lim¹, Hiranya Dayal², Song Jie Seah², Regina Pei Woon Tan², Zhi En Low², Anna Karen Carrasco Laserna³, Sock Hwee Tan⁴, Mark Y Chan⁴, Sam Fong Yau Li⁵

Affiliations

¹ NUS Graduate School's Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, University Hall, Tan Chin Tuan Wing, 119077, Singapore; Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
² Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
³ Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore; Central Instrument Facility, Office of the Vice Chancellor for Research and Innovation, De La Salle University, 2401 Taft Avenue, Malate, Manila 1004, Philippines.
⁴ Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
⁵ NUS Graduate School's Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, University Hall, Tan Chin Tuan Wing, 119077, Singapore; Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore. Electronic address: chmlifys@nus.edu.sg.

PMID: 36905853
DOI: 10.1016/j.jtemb.2023.127148

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, Ca×P, 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.

Keywords: Acute myocardial infarction; Biomarker; Cardiovascular disease; Copper; Coronary heart disease; ICP-MS; Ionomics; Metallomics; Selenium.

MeSH terms

Humans
Linear Models
Tandem Mass Spectrometry*
Trace Elements* / analysis

Substances

Trace Elements