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Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: a prospective cohort study.

ABSTRACT: Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated. This prospective, single-center cohort study enrolled 2090 hospitalized CAD patients confirmed by angiography at Beijing Hospital from 2017-2020. TMAO levels were performed using liquid chromatography-tandem mass spectrometry. The composite outcome of MACEs was identified by clinic visits or interviews annually. Multivariate Cox regression analysis, Kaplan-Meier analysis, and restricted cubic splines were mainly used to explore the relationship between TMAO levels and MACEs based on diabetes mellitus (DM) habitus. During the median follow-up period of 54 (41, 68) months, 266 (12.7%) developed MACEs. Higher TMAO levels, using the tertile cut-off value of 318.28 ng/mL, were significantly found to be positive dose-independent for developing MACEs, especially in patients with DM (HR 1.744, 95%CI 1.084-2.808, p = 0.022). Higher levels of TMAO are significantly associated with long-term MACEs among CAD patients with DM. The combination of TMAO in patients with CAD and DM is beneficial for risk stratification and prognosis.

SUBMITTER: Yu X

PROVIDER: S-EPMC11291261 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: a prospective cohort study.

Yu Xue X Wang Yijia Y Yang Ruiyue R Wang Zhe Z Wang Xinyue X Wang Siming S Zhang Wenduo W Dong Jun J Chen Wenxiang W Ji Fusui F Gao Wei W

Frontiers in endocrinology 20240718

<h4>Background</h4>Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated.<h4>Methods</h4>This prospective, single-center cohort study enrolled 20 ...[more]

PMID: 39092284

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Project description:BackgroundApolipoprotein CIII (apoCIII) is associated with triglyceride-rich lipoprotein metabolism and has emerged as independent marker for risk of cardiovascular disease. The objective was to test whether apoCIII is regulated postprandially and whether apoCIII concentrations in native and chylomicron-free serum predict future cardiovascular events in patients with stable coronary artery disease (CAD).MethodsApoCIII concentrations were measured in native and chylomicron-free serum in the fasting state and after a standardized oral fat load test in 195 patients with stable CAD. Clinical follow-up was 48 months. Chylomicron-free serum was prepared by ultracentrifugation (18,000 rpm, 3 h). The log-rank test and Cox regression analyses were used to investigate the association of apoCIII with recurrent cardiovascular events.ResultsOf the 195 patients included, 92 had a cardiovascular event, and 103 did not. 97% were treated with a statin. No significant changes in apoCIII concentration were observed after the oral fat load test. The apoCIII concentration was associated with event-free survival independent of conventional risk factors. This association reached statistical significance only for apoCIII concentration measured in chylomicron-free serum (hazard ratio [95% confidence interval] for apoCIII above the mean: postprandial: 1.67 (1.06-2.29), P = 0.028, fasting: 2.09 (1.32-3.32), P = 0.002), but not for apoCIII concentration measured in native serum (postprandial: 1.47 [0.89-2.43], P = 0.133, fasting: 1.56 [0.95-2.58], P = 0.081). The effects were independent of other risk factors.ConclusionsApoCIII concentrations in chylomicron-free serum are independently associated with event-free survival in patients with CAD both in fasting and postprandial state. This findings support considering apoCIII for risk assessment and attempting to test the hypothesis that lowering apoCIII reduces residual cardiovascular risk.Take home messageApolipoprotein CIII concentration measured in chylomicron-free serum predicts recurrent cardiovascular events in patients with stable coronary artery disease.Trial registrationThe trial which included the participants of this study was registered at https://clinicaltrials.gov (NCT00628524) on March 5, 2008.

Project description:BACKGROUND Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153–1888, 1888–3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52–3.11)], including: MI [HR = 2.83 95% CI: (1.03–7.74)], heart failure [HR = 2.71 95% CI: (1.18–6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49–4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

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Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: a prospective cohort study.

Publications

Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: a prospective cohort study.

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