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Title
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Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure)
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Author
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Abstract
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| Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes. Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression. Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism. Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research. |
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Language
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English
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Source (journal)
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Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals
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Publication
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2020
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ISSN
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1354-750X
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DOI
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10.1080/1354750X.2020.1727015
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Volume/pages
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25
:2
(2020)
, p. 201-211
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ISI
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000514420500001
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Pubmed ID
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32063068
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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