Nontargeted Metabolomics Revealed Novel Association Between Serum Metabolites and Incident Acute Coronary Syndrome: A Mendelian Randomization Study

Autor: Gaokun Qiu, Yuhui Lin, Yang Ouyang, Mingrong You, Xinjie Zhao, Hao Wang, Rundong Niu, Wending Li, Xuedan Xu, Qi Yan, Yurong Liu, Yingmei Li, Handong Yang, Xiulou Li, Meian He, Xiaomin Zhang, Xiao‐Ou Shu, Guowang Xu, Tangchun Wu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 12, Iss 13 (2023)
Druh dokumentu: article
ISSN: 2047-9980
DOI: 10.1161/JAHA.122.028540
Popis: Background This study was performed to identify metabolites associated with incident acute coronary syndrome (ACS) and explore causality of the associations. Methods and Results We performed nontargeted metabolomics in a nested case‐control study in the Dongfeng‐Tongji cohort, including 500 incident ACS cases and 500 age‐ and sex‐matched controls. Three metabolites, including a novel one (aspartylphenylalanine), and 1,5‐anhydro‐d‐glucitol (1,5‐AG) and tetracosanoic acid, were identified as associated with ACS risk, among which aspartylphenylalanine is a degradation product of the gut‐brain peptide cholecystokinin‐8 rather than angiotensin by the angiotensin‐converting enzyme (odds ratio [OR] per SD increase [95% CI], 1.29 [1.13–1.48]; false discovery rate–adjusted P=0.025), 1,5‐AG is a marker of short‐term glycemic excursions (OR per SD increase [95% CI], 0.75 [0.64–to 0.87]; false discovery rate–adjusted P=0.025), and tetracosanoic acid is a very‐long‐chain saturated fatty acid (OR per SD increase [95% CI], 1.26 [1.10–1.45]; false discovery rate–adjusted P=0.091). Similar associations of 1,5‐AG (OR per SD increase [95% CI], 0.77 [0.61–0.97]) and tetracosanoic acid (OR per SD increase [95% CI], 1.32 [1.06–1.67]) with coronary artery disease risk were observed in a subsample from an independent cohort (152 and 96 incident cases, respectively). Associations of aspartylphenylalanine and tetracosanoic acid were independent of traditional cardiovascular risk factors (P‐trend=0.015 and 0.034, respectively). Furthermore, the association of aspartylphenylalanine was mediated by 13.92% from hypertension and 27.39% from dyslipidemia (P
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