Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction.
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.
MedStar Washington Hospital Center, Georgetown University, Washington, DC 20010, USA.
Smita I
SI
Negi
Cardiovascular Research Center and Cardiovascular Institute of Lifespan, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.
Euy-Myoung
EM
Jeong
University of Illinois at Chicago, Chicago, IL 60612, USA.
Irfan
I
Shukrullah
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Emir
E
Veleder
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Dean P
DP
Jones
University of Tennessee, Memphis, TN 38163, USA.
Tai-Hwang M
TH
Fan
University of Illinois at Chicago, Chicago, IL 60612, USA.
Sudhahar
S
Varadarajan
University of Illinois at Chicago, Chicago, IL 60612, USA.
Sergei M
SM
Danilov
University of Illinois at Chicago, Chicago, IL 60612, USA.
Tohru
T
Fukai
Cardiovascular Research Center and Cardiovascular Institute of Lifespan, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.
Samuel C
SC
Dudley
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology*
D015415:Biomarkers