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Background: Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods: We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results: After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44–2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85–5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37–2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39–0.60)]. Conclusions: Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a common metabolic bone disease, which always leads to osteoporotic fractures. Biomarkers of bone mineral density (BMD) are helpful for prevention and early diagnosis of osteoporosis. This study aims to identify metabolomic biomarkers of low BMD., Methods: We included 701 participants who had BMD measures by dual-energy X-ray absorptiometry scans and donated fasting plasma samples from three clinical centres as a discovery set and another 278 participants from the fourth centre as an independent replication set. We used a liquid chromatography-mass spectrometry-based metabolomics approach to profile the global metabolites of fasting plasma., Findings: Among the 265 named metabolites identified in our study, six were associated with low BMD (FDR-adjusted P<0.05) in the discovery set and were successfully validated in the independent replication set. The circulating levels of five metabolites, i.e., inosine, hypoxanthine, PC (O-18:0/22:6), SM (d18:1/21:0) and isoleucyl-proline were associated with decreased odds of low BMD, and PC (16:0/18:3) level was associated with increased odds of low BMD. Per 1-SD increase in a composite metabolite score of these six metabolites was associated with about half decreased odds of low BMD (odds ratio 0.59, 95% confidence interval: 0.52-0.68). Furthermore, introduction of a panel of metabolites selected by elastic net regression to a prediction model of classical risk factors and plasma biomarker of bone resorption substantially improved the prediction performance for low BMD (AUCs: 0.782 vs. 0.698, P=0.002)., Interpretation: Metabolomics profiling may help identify novel biomarkers of low BMD and be helpful for early diagnosis of osteoporosis beyond the current clinical index., Funding: This study was supported by the National Key R&D Program of China [2018YFC2001500 to J.S.], Shanghai Municipal Science and Technology Major Project [2017SHZDZX01], the National Natural Science Foundation of China [Key Program, 91749204 to J.S.], the National Natural Science Foundation of China [General Program, 81771491 to J.S.], the Project of Shanghai Subject Chief Scientist [2017BR011 to J.S.], Grants from the TCM Supported Project [18431902300 to J.S.] from the Science and Technology Commission of Shanghai Municipality, and the National Natural Science Foundation of China [General Program, 81972089 to Z.X.]. Y.Z. was supported by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, and the National Natural Science Foundation of China [81973032]., Competing Interests: Declaration of Competing Interests The authors have nothing to disclose. The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality. Methods: We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis. Results: In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions, P for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72), P =0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91), P =0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality. Conclusions: In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)