TY - JOUR
T1 - Effect of Heart Failure With Preserved Ejection Fraction on Nitric Oxide Metabolites
AU - Zamani, Payman
AU - French, Benjamin
AU - Brandimarto, Jeffrey A.
AU - Doulias, Paschalis Thomas
AU - Javaheri, Ali
AU - Chirinos, Julio A.
AU - Margulies, Kenneth B.
AU - Townsend, Raymond R.
AU - Sweitzer, Nancy K.
AU - Fang, James C.
AU - Ischiropoulos, Harry
AU - Cappola, Thomas P.
N1 - Funding Information:
Dr. Zamani received funding from the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania, grant number 5UL1TR000003-09 from the National Center for Research Resources, 5-T32-HL007843-17, and 1-K23-HL-130551-01; Dr. Cappola received funding from the National Institutes of Health (NIH) (R01HL08577), BG Medicine, and Abbott Diagnostics. Dr. Chirinos served as a consultant to Bristol Myers Squibb, OPKO Healthcare, Fukuda Denshi, Microsoft, and Merck; received research grants R56HL-124073-01A1, R01 HL 121510-01A1, and 5-R21-AG-043802-02 from NIH, American College of Radiology Network, Fukuda Denshi, Bristol Myers Squibb, Microsoft, and CVRx Inc. and a device loan from Atcor Medical; and named as inventor in a University of Pennsylvania patent application for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction; Dr. Margulies: research grant, modest: Juventis Therapeutics, Celladon Corporation, Thoratec Corporation, Innolign Biomedical, LLC; research grant, significant: Merck, Inc., consultant/Advisory Board, modest: NovoNordisk (unpaid), Janssen, Merck, Pfizer, Ridgetop Research, AstraZeneca; Dr. Townsend served as a consultant for Medtronic, Fukuda Denshii, and Relypsa; received funding from the NIH. Dr. Ischiropoulos received grants from the National Institutes of Health (NIH HL54926) and innovation award from Sanofi and the Gisela and Dennis Alter Research Professor of Pediatrics; Dr. Javaheri is supported by 5T32HL007081-40. The other authors have no conflict of interest to declare.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - 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 NOm in 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 NOm levels 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 NOm levels 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 NOm in HFpEF, whereas age (+11%/10-year increase, p = 0.03), current tobacco use (+67%, p = 0.01), and eGFR (p = 0.01) associated with NOm in Recovered-HF. In conclusion, HFpEF participants have reduced NOm compared with HFrEF in this matched cohort. This might suggest either compromised endothelial function or poor dietary intake. Black race was associated with lower NOm in HFpEF.
AB - 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 NOm in 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 NOm levels 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 NOm levels 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 NOm in HFpEF, whereas age (+11%/10-year increase, p = 0.03), current tobacco use (+67%, p = 0.01), and eGFR (p = 0.01) associated with NOm in Recovered-HF. In conclusion, HFpEF participants have reduced NOm compared with HFrEF in this matched cohort. This might suggest either compromised endothelial function or poor dietary intake. Black race was associated with lower NOm in HFpEF.
UR - http://www.scopus.com/inward/record.url?scp=84998880867&partnerID=8YFLogxK
U2 - 10.1016/j.amjcard.2016.08.077
DO - 10.1016/j.amjcard.2016.08.077
M3 - Article
C2 - 27742422
AN - SCOPUS:84998880867
VL - 118
SP - 1855
EP - 1860
JO - American Journal of Cardiology
JF - American Journal of Cardiology
SN - 0002-9149
IS - 12
ER -