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Author Notes:

Correspondence should be addressed to Samuel C. Dudley Jr.; samuel dudley@brown.edu

Disclosure: Samuel C. Dudley Jr. is the inventor of patent applications: (1) 11/895,883 Methods and Compositions for Treating Diastolic Dysfunction, (2) 13/503,812 Methods of Diagnosing Diastolic Dysfunction, (3) 13/397,622 Methods for Treating Diastolic Dysfunction and Related Conditions, (4) 13/658,943 Method of Improving Diastolic Dysfunction, (5) 13/841,843 Myosin Binding Protein-C for Use in Methods Relating to Diastolic Heart Failure, and (6) 61/728,302 Mitochondrial Antioxidants and Diabetes.

The authors declare that there is no conflict of interests regarding the publication of this paper.


Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction.


Journal Title:

BioMed Research International


Volume 2015


, Pages 825027-825027

Type of Work:

Article | Final Publisher PDF


Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione (E h GSH) and cysteine (E h CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p = 0.04), higher body mass index (BMI) (p = 0.003), less oxidized E h CyS (p = 0.001), lower DROMs (p = 0.02), and lower IsoP (p = 0.03). Higher BMI (OR: 1.3; 95% CI: 1.1-1.6) and less oxidized E h CyS (OR: 1.2; 95% CI: 1.1-1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01-1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF.

Copyright information:

© 2015 Smita I. Negi et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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