AUTHOR=Dehghanbanadaki Hojat , Dodangeh Salimeh , Parhizkar Roudsari Peyvand , Hosseinkhani Shaghayegh , Khashayar Pouria , Noorchenarboo Mohammad , Rezaei Negar , Dilmaghani-Marand Arezou , Yoosefi Moein , Arjmand Babak , Khalagi Kazem , Najjar Niloufar , Kakaei Ardeshir , Bandarian Fatemeh , Aghaei Meybodi Hamid , Larijani Bagher , Razi Farideh 

TITLE=Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1161761

DOI=10.3389/fcvm.2023.1161761

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>The intermediate metabolites associated with the development of atherosclerotic cardiovascular disease (ASCVD) remain largely unknown. Thus, we conducted a large panel of metabolomics profiling to identify the new candidate metabolites that were associated with 10-year ASCVD risk.</p></sec><sec><title>Methods</title><p>Thirty acylcarnitines and twenty amino acids were measured in the fasting plasma of 1,102 randomly selected individuals using a targeted FIA-MS/MS approach. The 10-year ASCVD risk score was calculated based on 2013 ACC/AHA guidelines. Accordingly, the subjects were stratified into four groups: low-risk (<italic>n</italic> = 620), borderline-risk (<italic>n</italic> = 110), intermediate-risk (<italic>n</italic> = 225), and high-risk (<italic>n</italic> = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis.</p></sec><sec><title>Results</title><p>C<sub>4</sub>DC, C<sub>8:1</sub>, C<sub>16</sub>OH, citrulline, histidine, alanine, threonine, glycine, glutamine, tryptophan, phenylalanine, glutamic acid, arginine, and aspartic acid were significantly associated with the 10-year ASCVD risk score (<italic>p</italic>-values ≤ 0.044). The high-risk group had higher odds of factor 1 (12 long-chain acylcarnitines, OR = 1.103), factor 2 (5 medium-chain acylcarnitines, OR = 1.063), factor 3 (methionine, leucine, valine, tryptophan, tyrosine, phenylalanine, OR = 1.074), factor 5 (6 short-chain acylcarnitines, OR = 1.205), factor 6 (5 short-chain acylcarnitines, OR = 1.229), factor 7 (alanine, proline, OR = 1.343), factor 8 (C<sub>18:2</sub>OH, glutamic acid, aspartic acid, OR = 1.188), and factor 10 (ornithine, citrulline, OR = 1.570) compared to the low-risk ones; the odds of factor 9 (glycine, serine, threonine, OR = 0.741), however, were lower in the high-risk group. “D-glutamine and D-glutamate metabolism”, “phenylalanine, tyrosine, and tryptophan biosynthesis”, and “valine, leucine, and isoleucine biosynthesis” were metabolic pathways having the highest association with borderline/intermediate/high ASCVD events, respectively.</p></sec><sec><title>Conclusions</title><p>Abundant metabolites were found to be associated with ASCVD events in this study. Utilization of this metabolic panel could be a promising strategy for early detection and prevention of ASCVD events.</p></sec>