Defining Acute Coronary Syndrome through Metabolomics

Surendran, Arun; Atefi, Negar; Zhang, Hannah; Aliani, Michel; Ravandi, Amir

doi:10.3390/metabo11100685

Cited by 19 publications

(19 citation statements)

References 171 publications

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“…The question of whether arterial and venous thrombosis are just two different clinical manifestations on the continuum of the same disease [ 49 ] remains to be answered. Plasma metabolomic studies from patients diagnosed with coronary syndrome identified upregulation of 2-OH-butyric acid, a glutathione presynthesis byproduct under hypoxia [ 50 , 51 ], in line with our findings of higher glutathione levels in RBCs from acute VTE patients. Purine metabolism has also been associated with unstable angina [ 52 , 53 ], metabolic syndrome and all-cause mortality [ 54 – 56 ], and venous thrombosis [ 57 , 58 ].…”

Section: Discussionsupporting

confidence: 87%

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

Febra,

Saraiva,

Vaz

et al. 2024

J Transl Med

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Background Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was d-glutamine and d-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3′,5′-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

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Section: Discussionsupporting

confidence: 87%

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

Febra,

Saraiva,

Vaz

et al. 2024

J Transl Med

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“…To improve management and therapy of ACS, effective tools for risk assessment in secondary prevention are needed. Since ACS frequently exhibits metabolic alterations, a metabolomics approach might play a significant role in the better management of ACS patients, by advancing our understanding of the mechanisms underlying the increased risk of recurrent cardiovascular events following ACS and helping in the identification of biomarkers related to these adverse events [4].…”

Section: Introductionmentioning

confidence: 99%

Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome

Mateu-Fabregat,

Mostafa,

Sanchez-Gimenez

et al. 2024

Nutrients

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The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12–1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

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“…Prognostic classification in patients admitted with ACS is necessary for providing efficient follow-up and guiding treatment. During the last years, many efforts have been made to identify predictive biomarkers for adverse outcomes following ACS ( 2 ) and metabolomics seems a promising approach ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function

Sánchez-Giménez

Peiró

Bonet

et al. 2023

Front. Cardiovasc. Med.

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AimsTo examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations.MethodsThis is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR).ResultsAfter adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations.ConclusionThese findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications.

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Defining Acute Coronary Syndrome through Metabolomics

Cited by 19 publications

References 171 publications

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study

Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome

TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function

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