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. 2022 Jul;19(4):287-297.
doi: 10.2217/pme-2021-0021. Epub 2022 Apr 25.

A precision medicine approach to stress testing using metabolomics and microribonucleic acids

Alexander T Limkakeng  1 , Laura-Leigh Rowlette  2 , Ace Hatch  3 , Andrew B Nixon  3 , Olga Ilkayeva  4   5 , David Corcoran  6 , Jennifer Modliszewski  6 , Shannon Michelle Griffin  1 , Geoffrey S Ginsburg  7   8 , Deepak Voora  7   8
Affiliations

A precision medicine approach to stress testing using metabolomics and microribonucleic acids

Alexander T Limkakeng et al. Per Med. 2022 Jul.

Abstract

Both transcriptomics and metabolomics hold promise for identifying acute coronary syndrome (ACS) but they have not been used in combination, nor have dynamic changes in levels been assessed as a diagnostic tool. We assessed integrated analysis of peripheral blood miRNA and metabolite analytes to distinguish patients with myocardial ischemia on cardiac stress testing. We isolated and quantified miRNA and metabolites before and after stress testing from seven patients with myocardial ischemia and 1:1 matched controls. The combined miRNA and metabolomic data were analyzed jointly in a supervised, dimension-reducing discriminant analysis. We implemented a baseline model (T0) and a stress-delta model. This novel integrative analysis of the baseline levels of metabolites and miRNA expression showed modest performance for distinguishing cases from controls. The stress-delta model showed worse performance. This pilot study shows potential for an integrated precision medicine approach to cardiac stress testing.

Keywords: acute coronary syndrome; biomarkers; metabolomics; miRNA; precision medicine; stress test; transcriptomics.

Plain language summary

The study of small sequences of ribonucleic acids (miRNAs) and byproducts of cellular metabolism (metabolites) could help us to identify important cardiac conditions such as not enough blood and oxygen supply to the heart (acute coronary syndrome). We obtained blood samples from patients getting cardiac stress tests (a noninvasive test to see if the patient has enough blood flow to their heart) before and after their test, then compared the levels of miRNAs and metabolites in them. We compared the levels in patients who had abnormal stress tests with those that had normal tests. We believe this could be a model for a new type of cardiac stress test if validated in more patients.

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