scholarly journals Trimethyllysine, a trimethylamine N-oxide precursor, provides near- and long-term prognostic value in patients presenting with acute coronary syndromes

2019 ◽  
Vol 40 (32) ◽  
pp. 2700-2709 ◽  
Author(s):  
Xinmin S Li ◽  
Slayman Obeid ◽  
Zeneng Wang ◽  
Benjamin J Hazen ◽  
Lin Li ◽  
...  
Keyword(s):  
Chest Pain ◽  
Acute Coronary Syndromes ◽  
Troponin T ◽  
High Sensitivity ◽  
Cardiac Events ◽  
Adverse Cardiac Events ◽  
All Cause Mortality ◽  
Coronary Syndromes ◽  
High Sensitivity Troponin T

AbstractAims Trimethyllysine (TML) serves as a nutrient precursor of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and is associated with incident cardiovascular (CV) events in stable subjects. We examined the relationship between plasma TML levels and incident CV events in patients presenting with acute coronary syndromes (ACS).Methods and results Plasma levels of TML were quantified in two independent cohorts using mass spectrometry, and its relationship with CV events was investigated. In a Cleveland Cohort (N = 530), comprised of patients presenting to the emergency department with chest pain and suspected ACS, TML was associated with major adverse cardiac events (MACE, myocardial infarction, stroke, need for revascularization, or all-cause mortality) over both 30 days [3rd tertile (T3), adjusted odds ratio (OR) 1.77, 95% confidence interval (CI) 1.04–3.01; P < 0.05] and 6 months (T3, adjusted OR 1.95, 95% CI 1.15–3.32; P < 0.05) of follow-up independent of traditional CV risk factors and indices of renal function. Elevated TML levels were also associated with incident long-term (7-year) all-cause mortality [T3, adjusted hazard ratio (HR) 2.52, 95% CI 1.50–4.24; P < 0.001], and MACE even amongst patients persistently negative for cardiac Troponin T at presentation (e.g. 30-day MACE, T3, adjusted OR 4.49, 95% CI 2.06–9.79; P < 0.001). Trimethyllysine in combination with TMAO showed additive significance for near- and long-term CV events, including patients with ‘negative’ high-sensitivity Troponin T levels. In a multicentre Swiss Cohort (N = 1683) comprised of ACS patients, similar associations between TML and incident 1-year adverse cardiac risks were observed (e.g. mortality, adjusted T3 HR 2.74, 95% CI 1.28–5.85; P < 0.05; and MACE, adjusted T3 HR 1.55, 95% CI 1.04–2.31; P < 0.05).Conclusion Plasma TML levels, alone and together with TMAO, are associated with both near- and long-term CV events in patients with chest pain and ACS.

scholarly journals Early overexpression of miR-499 in non-ST elevation acute coronary syndromes predicts long-term risk of major adverse cardiac events

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Miskowiec ◽  
K Kupczynska ◽  
M Simiera ◽  
B Michalski ◽  
D Filipiak-Strzecka ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Troponin T ◽  
High Sensitivity ◽  
Funding Source ◽  
Cardiac Events ◽  
Adverse Cardiac Events ◽  
Median Level ◽  
High Sensitivity Troponin T

Abstract Background Some studies reported utility of microRNAs in myocardial infarction diagnostic process, whereas their prognostic remains unclear. Aim To evaluate the prognostic value of five circulating miRs (miR-1, miR-21, miR-133a, miR-208, miR-499) levels for predicting major adverse cardiac events (MACE), including death, nonfatal myocardial infarction (MI) or cardiovascular rehospitalization (reh.) in patients with NSTE-ACS. Material and methods In our prospective, single-center observational study we recruited patients (pts) with NSTE-ACS with symptoms onset &lt;24 hours before the hospital admission and age, gender-matched patients with stable coronary artery disease (SCAD) as controls. Blood was sampled twice (at admission and 4h after in NSTE-ACS and once in SCAD). Relative expression of miRs were calculated using the ΔΔCt method after normalization to the cel-miR-39 spiked-in control. The mean value of miRs relative expression from two time samples in NSTE-ACS pts were used for further analysis. Subjects were categorized according to mean miRs expression at hospital admission into two group (≤ or &gt; median level of miRs). Results 103 NSTE-ACS pts (median age 67 years, 68% male) were included in this study. During median 1569 (IQR 935–1842) days of follow-up the primary endpoint (MACE) occurred in 66 (64.1%) pts: 18 pts (18.7%) died, 30 pts (20%) presented with MI and 85 pts (56.7%) were readmitted. In a Cox proportional-hazards regression model miR-499 expression &gt; median level (HR=1.82, 95% CI 1.07–3.09) and high-sensitivity troponin T level (HR=1.24, 95% CI 1.05–1.46) were independent predictors of MACE in long term observation, even after adjustment for other covariates (including other miRNAs). Incidence of MI [34% vs 10%, HR=4.1 (2.0–8.5)], rehospitalization for cardiovascular reasons [67% vs 49%, HR=2.1 (1.3–3.3)] and MACE [76% vs 55%, HR=2.2 (1.5–3.5)] was significantly higher in pts with elevated (&gt; median) miR-499 levels at hospital admission. None of analyzed miRNAs was related to long-term mortality, whereas the left ventricular ejection fraction (EF) has been identified as the only one survival predictor (HR=0.95, 95% CI 0.92–0.98). Conclusions Elevated miR-499 levels independently of high sensitivity troponin T levels in early phase of NSTE-ACS are related to increased rate of MACE in 4-year follow-up. Figure 1. miR499 and MACE Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Polish Ministry of Science and Higher Education “Diamond Grant” program.

scholarly journals Cysteine‐Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes

2021 ◽  
Author(s):  
Roland Klingenberg ◽  
Soheila Aghlmandi ◽  
Lorenz Räber ◽  
Alexander Akhmedov ◽  
Baris Gencer ◽  
...  
Keyword(s):  
Risk Score ◽  
Acute Coronary Syndromes ◽  
Troponin T ◽  
High Sensitivity ◽  
Prognostic Accuracy ◽  
Grace Risk Score ◽  
All Cause Mortality ◽  
Coronary Syndromes ◽  
Coronary Events ◽  
High Sensitivity Troponin T

Background It remains unclear whether the novel biomarker cysteine‐rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high‐sensitivity Troponin T, hsCRP (high‐sensitivity C‐reactive protein), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) in patients with acute coronary syndromes. Methods and Results Patients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine – Acute Coronary Syndromes and Inflammation cohort. The primary/secondary end points were 30‐day/1‐year all‐cause mortality and the composite of all‐cause mortality or myocardial infarction as used in the GRACE risk score. Associations between biomarkers and outcome were assessed using log‐transformed biomarker values and the GRACE risk score (versions 1.0 and 2.0). The incremental value of CCN1 beyond a reference model was assessed using Harrell’s C‐statistics calculated from a Cox proportional‐hazard model. The P value of the C‐statistics was derived from a likelihood ratio test. Among 2168 patients recruited, 1732 could be analyzed. CCN1 was the strongest single predictor of all‐cause mortality at 30 days (hazard ratio [HR], 1.77 [1.31, 2.40]) and 1 year (HR, 1.81 [1.47, 2.22]). Adding CCN1 alone to the GRACE 2.0 risk score improved C‐statistics for prognostic accuracy of all‐cause mortality at 30 days (0.87–0.88) and 1 year (0.81–0.82) and when combined with high‐sensitivity Troponin T, hsCRP, NT‐proBNP for 30 days (0.87–0.91), and for 1‐year follow‐up (0.81–0.84). CCN1 also increased the prognostic value for the composite of all‐cause mortality or myocardial infarction. Conclusions CCN1 predicts adverse outcomes in patients with acute coronary syndromes adding incremental information to the GRACE risk score, suggesting distinct underlying molecular mechanisms. Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01000701.

scholarly journals High-Sensitivity Troponin T and Copeptin in Non-ST Acute Coronary Syndromes: Implications for Prognosis and Role of hsTnT and Copeptin in Non-STEACS

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Diana Hernández-Romero ◽  
José María García-Salas ◽  
Ángel López-Cuenca ◽  
Patricio Pérez-Berbel ◽  
Carmen Puche ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acute Coronary Syndromes ◽  
Troponin T ◽  
High Sensitivity ◽  
Healthy Controls ◽  
Invasive Approach ◽  
Coronary Syndromes ◽  
Prognostic Implications ◽  
High Sensitivity Troponin T

High-sensitivity TnT (hsTnT) has been proposed to improve the diagnosis and stratification in acute coronary syndromes. Copeptin has been proposed for a rapid and accurate rule out of acute myocardial infarction, but some doubts exist about its use out of the first hours from admission. Abnormalities of serum hsTnT and copeptin levels in non-STEACS and negative TnT, could have prognostic implications.Methods. We included 122 non-STEACS patients without raised TnT, 33 disease controls and 43 healthy controls. We measured hsTnT and copeptin levels. Clinical follow-up at 12 months was performed for adverse endpoints.Results. Non-STEACS patients had raised hsTnT compared with both control groups (P=0.036andP<0.001). Copeptin levels were higher in non-STEACS patients than healthy controls (P=0.021), without differences with disease controls. Raised levels of hs-TnT presented prognostic implications [HR 3.29 (95%CI: 1.33–7.49),P=0.010]. hs-TnT could be used for invasive approach decision, as it shows prognostic relevance in conservative approach-patients whereas remains unrelevant for catheterized-patients. Copeptin levels were not associated with adverse events.Conclusion. hsTnT levels increased in non-STEACS, were predictive of adverse events and could be important for recommending an invasive management. We cannot confirm a predictive role of copeptin out of the first hours from admission.

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