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BioMed Research International
Volume 2015 (2015), Article ID 825027, 7 pages
Research Article

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

1MedStar Washington Hospital Center, Georgetown University, Washington, DC 20010, USA
2Cardiovascular Research Center and Cardiovascular Institute of Lifespan, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
3University of Illinois at Chicago, Chicago, IL 60612, USA
4Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
5Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
6University of Tennessee, Memphis, TN 38163, USA

Received 20 March 2015; Revised 3 June 2015; Accepted 10 June 2015

Academic Editor: Giacomo Frati

Copyright © 2015 Smita I. Negi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 ( GSH) and cysteine ( CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex , higher body mass index (BMI) , less oxidized CyS , lower DROMs , and lower IsoP . Higher BMI (OR: 1.3; 95% CI: 1.1–1.6) and less oxidized 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.