Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial
The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomar...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2796 |
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| author | Moritz Schnelle Andreas Leha Abass Eidizadeh Katharina Fuhlrott Tobias D. Trippel Djawid Hashemi Karl Toischer Rolf Wachter Christoph Herrmann-Lingen Gerd Hasenfuß Burkert Pieske Lutz Binder Frank Edelmann |
| author_facet | Moritz Schnelle Andreas Leha Abass Eidizadeh Katharina Fuhlrott Tobias D. Trippel Djawid Hashemi Karl Toischer Rolf Wachter Christoph Herrmann-Lingen Gerd Hasenfuß Burkert Pieske Lutz Binder Frank Edelmann |
| author_sort | Moritz Schnelle |
| collection | DOAJ |
| description | The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO<sub>2</sub>. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement. |
| first_indexed | 2024-03-10T06:39:17Z |
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| language | English |
| last_indexed | 2024-03-10T06:39:17Z |
| publishDate | 2021-10-01 |
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| series | Cells |
| spelling | doaj.art-2e7a3ff46bfd4d69b40101c1a2e614bd2023-11-22T17:49:20ZengMDPI AGCells2073-44092021-10-011010279610.3390/cells10102796Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF TrialMoritz Schnelle0Andreas Leha1Abass Eidizadeh2Katharina Fuhlrott3Tobias D. Trippel4Djawid Hashemi5Karl Toischer6Rolf Wachter7Christoph Herrmann-Lingen8Gerd Hasenfuß9Burkert Pieske10Lutz Binder11Frank Edelmann12Institute for Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, 37075 Goettingen, GermanyInstitute for Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, GermanyClinic of Cardiology and Pneumology, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, 37075 Goettingen, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, 37075 Goettingen, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, 37075 Goettingen, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, 37075 Goettingen, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyInstitute for Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyThe pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO<sub>2</sub>. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement.https://www.mdpi.com/2073-4409/10/10/2796plasma biomarkersheart failure with preserved ejection fractionspironolactone |
| spellingShingle | Moritz Schnelle Andreas Leha Abass Eidizadeh Katharina Fuhlrott Tobias D. Trippel Djawid Hashemi Karl Toischer Rolf Wachter Christoph Herrmann-Lingen Gerd Hasenfuß Burkert Pieske Lutz Binder Frank Edelmann Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial Cells plasma biomarkers heart failure with preserved ejection fraction spironolactone |
| title | Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial |
| title_full | Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial |
| title_fullStr | Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial |
| title_full_unstemmed | Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial |
| title_short | Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial |
| title_sort | plasma biomarker profiling in heart failure patients with preserved ejection fraction before and after spironolactone treatment results from the aldo dhf trial |
| topic | plasma biomarkers heart failure with preserved ejection fraction spironolactone |
| url | https://www.mdpi.com/2073-4409/10/10/2796 |
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