title: Effect of Heart Failure With Preserved Ejection Fraction on Nitric Oxide Metabolites.
abstract: Endothelial function may be deranged in heart failure with preserved ejection fraction (HFpEF). Serum NO-derived metabolites (NOm) might provide a biochemical surrogate of endothelial function in patients with heart failure (HF). We measured serum NOmin 415 participants in the Penn HF Study. Participants with HFpEF (n = 82) and those whose EF had recovered (Recovered-HF, n = 125) were matched 1:1 to heart failure with reduced ejection fraction (HFrEF) participants based on age, gender, race, tobacco use, and eGFR. Serum NOmlevels were quantified after chemical reduction coupled with gas-phase chemiluminescence detection. After adjustment for matching covariates and BMI, HFpEF (34.5 μM; interquartile range [IQR] 25.0, 51.5) participants had lower NOmlevels than HFrEF (41.0 μM; IQR 28.3, 58.0; ratio of HFpEF:HFrEF 0.82, 95% confidence interval [CI] 0.67 to 0.99; p = 0.04), which further decreased when adjusted for covariates that affect endothelial function (ratio 0.79, 95% CI 0.65 to 0.98; p = 0.03). There were no differences between HFrEF (34.0; IQR 25.3, 49.0) and matched Recovered-HF (36.0 μM; IQR 25.0, 55.0) or HFpEF and Recovered-HF. Age (+21%/10-year increase, p <0.001) and black race (-28%, p = 0.03) associated with NOmin HFpEF, whereas age (+11%/10-year increase, p = 0.03), current tobacco use (+67%, p = 0.01), and eGFR (p = 0.01) associated with NOmin Recovered-HF. In conclusion, HFpEF participants have reduced NOmcompared with HFrEF in this matched cohort. This might suggest either compromised endothelial function or poor dietary intake. Black race was associated with lower NOmin HFpEF.
authors.affiliation: Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: pzamani@upenn.edu.
authors.forename: Payman
authors.initials: P
authors.lastname: Zamani
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.affiliation: Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Brandimarto
authors.affiliation: Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
authors.forename: Paschalis-Thomas
authors.initials: PT
authors.lastname: Doulias
authors.affiliation: Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ali
authors.initials: A
authors.lastname: Javaheri
authors.affiliation: Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Chirinos
authors.affiliation: Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
authors.affiliation: Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: Division of Cardiovascular Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
authors.affiliation: Division of Cardiovascular Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: James C
authors.initials: JC
authors.lastname: Fang
authors.affiliation: Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
authors.affiliation: Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
mesh_terms: D000367:Age Factors; D000368:Aged; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology; D012907:Smoking / Q000097:blood / Q000453:epidemiology; D016277:Ventricular Function, Left
chemical_list: D009569:Nitric Oxide