Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study
Background While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify prote...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.029980 |
| _version_ | 1827592647871561728 |
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| author | Ravi V. Shah Shih‐Jen Hwang Venkatesh L. Murthy Shilin Zhao Kahraman Tanriverdi Priya Gajjar Kevin Duarte Mark Schoenike Robyn Farrell Liana C. Brooks Deepa M. Gopal Jennifer E. Ho Nicholas Girerd Ramachandran S. Vasan Daniel Levy Jane E. Freedman Gregory D. Lewis Matthew Nayor |
| author_facet | Ravi V. Shah Shih‐Jen Hwang Venkatesh L. Murthy Shilin Zhao Kahraman Tanriverdi Priya Gajjar Kevin Duarte Mark Schoenike Robyn Farrell Liana C. Brooks Deepa M. Gopal Jennifer E. Ho Nicholas Girerd Ramachandran S. Vasan Daniel Levy Jane E. Freedman Gregory D. Lewis Matthew Nayor |
| author_sort | Ravi V. Shah |
| collection | DOAJ |
| description | Background While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. Methods and Results We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins), and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O2 extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50–0.90] and 1.43 [95% CI, 1.11–1.85], respectively) with adjustment for clinical factors and B‐type natriuretic peptides. Conclusions The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis. |
| first_indexed | 2024-03-09T01:58:26Z |
| format | Article |
| id | doaj.art-2306c9218f714b4c81c636939db51d48 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-09T01:58:26Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2306c9218f714b4c81c636939db51d482023-12-08T11:09:10ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-11-01122110.1161/JAHA.122.029980Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot StudyRavi V. Shah0Shih‐Jen Hwang1Venkatesh L. Murthy2Shilin Zhao3Kahraman Tanriverdi4Priya Gajjar5Kevin Duarte6Mark Schoenike7Robyn Farrell8Liana C. Brooks9Deepa M. Gopal10Jennifer E. Ho11Nicholas Girerd12Ramachandran S. Vasan13Daniel Levy14Jane E. Freedman15Gregory D. Lewis16Matthew Nayor17Vanderbilt Translational and Clinical Research Center, Cardiology Division Vanderbilt University Medical Center Nashville TNPopulation Sciences Branch, Division of Intramural Research National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda MDDepartments of Medicine and Radiology University of Michigan Medical School Ann Arbor MIVanderbilt Center for Quantitative Sciences Vanderbilt University Medical Center Nashville TNVanderbilt Translational and Clinical Research Center, Cardiology Division Vanderbilt University Medical Center Nashville TNCardiology Section, Department of Medicine Boston University School of Medicine Boston MAUniversité de Lorraine, Centre d’Investigations Cliniques Plurithématique 1433, INSERM 1116 Nancy FranceCardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School Boston MACardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School Boston MACardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School Boston MACardiology Section, Department of Medicine Boston University School of Medicine Boston MACardioVascular Institute and Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center Boston MAUniversité de Lorraine, Centre d’Investigations Cliniques Plurithématique 1433, INSERM 1116 Nancy FranceUniversity of Texas School of Public Health San Antonio, and Departments of Medicine and Population Health Sciences, University of Texas Health Science Center San Antonio TXPopulation Sciences Branch, Division of Intramural Research National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda MDVanderbilt Translational and Clinical Research Center, Cardiology Division Vanderbilt University Medical Center Nashville TNCardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School Boston MACardiology Section, Department of Medicine Boston University School of Medicine Boston MABackground While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. Methods and Results We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins), and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O2 extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50–0.90] and 1.43 [95% CI, 1.11–1.85], respectively) with adjustment for clinical factors and B‐type natriuretic peptides. Conclusions The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.https://www.ahajournals.org/doi/10.1161/JAHA.122.029980biomarkersexercisehemodynamicsHFpEFproteomics |
| spellingShingle | Ravi V. Shah Shih‐Jen Hwang Venkatesh L. Murthy Shilin Zhao Kahraman Tanriverdi Priya Gajjar Kevin Duarte Mark Schoenike Robyn Farrell Liana C. Brooks Deepa M. Gopal Jennifer E. Ho Nicholas Girerd Ramachandran S. Vasan Daniel Levy Jane E. Freedman Gregory D. Lewis Matthew Nayor Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease biomarkers exercise hemodynamics HFpEF proteomics |
| title | Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study |
| title_full | Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study |
| title_fullStr | Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study |
| title_full_unstemmed | Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study |
| title_short | Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study |
| title_sort | proteomics and precise exercise phenotypes in heart failure with preserved ejection fraction a pilot study |
| topic | biomarkers exercise hemodynamics HFpEF proteomics |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.029980 |
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