Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score
Hojat Dehghanbanadaki, Salimeh Dodangeh, Peyvand Parhizkar Roudsari, Shaghayegh Hosseinkhani, Pouria Khashayar, Mohammad Noorchenarboo, Negar Rezaei, Arezou Dilmaghani‐Marand, Moein Yoosefi, Babak Arjmand, Kazem Khalagi, Niloufar Najjar, Ardeshir Kakaei, Fatemeh Bandarian, Hamid Aghaei Meybodi, Bagher Larijani, Farideh Razi
Abstract
Background 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. Methods 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 ( n = 620), borderline-risk ( n = 110), intermediate-risk ( n = 225), and high-risk ( n = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis. Results C 4 DC, C 8:1 , C 16 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 ( p -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 18:2 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. Conclusions 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.