Prognostic Value of Gut Microbe-Generated Metabolite Phenylacetylglutamine in Patients with Heart Failure
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Background: Phenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to hear failure (HF)-relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF. Methods and results: Fasting plasma PAGln levels were measured by stable-isotope-dilution LC-MS/MS in patients with stable HF from two large cohorts. All- cause mortality was assessed at 5-year follow up in the Cleveland Cohort, and HF, hospitalization, or mortality were assessed at 3-year follow up in the Berlin Cohort. Fasting PAGln levels were measured by stable-isotope-dilution LC-MS/MS.Within the Cleveland cohort, median PAGln levels were 4.2[IQR 2.4-6.9] μM. Highest quartile of PAGln was associated with 3.09-fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, eGFR, NT-proBNP, hsCRP, LV ejection fraction, ischemic etiology, and heart failure drug treatment, elevated PAGln levels remained predictive of 5-year mortality in quartile comparisons (adjusted Hazard Ratio[95%CI] for Q4vQ1: 1.64 [1.07-2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 μM [IQR 2.0-4.8] μM), and PAGln levels were associated with a 1.94-fold increase in 3-year HF hospitalization or all-cause mortality risk (adjusted HR [95%CI] for Q4vQ1: 1.94 [1. 14-3.28]). Prognostic value of PAGln appears to be independent of trimethylamine N-oxide levels. Conclusion: High levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio-renal risk markers.
Originalsprog | Engelsk |
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Tidsskrift | European Journal of Heart Failure |
Vol/bind | 26 |
Udgave nummer | 2 |
Sider (fra-til) | 233-241 |
ISSN | 1567-4215 |
DOI | |
Status | Udgivet - 2024 |
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