Abstract 14934: Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites
Stable plasma nitric oxide (NO) metabolites (NOM), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NOM levels integrate the influence of NO-synthase-derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NOM. Furthermore, nitrate and nitrate, the most abundant NOM, can be reduced to NO via the nitrate-nitrite-NO pathway. We compared serum NOM between subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43) and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NOM levels were measured after reduction to NO via the reaction with vanadium(III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower levels of NOM (8.0; μM; 95%CI=6.2-10.4 μM; ANOVA P=0.013) than subjects without HF (12.0; μM; 95%CI=10.4-13.9 μM; P=0.025) or those with HFrEF (13.5; μM; 95%CI=9.7-18.9 μM; P=0.03). There were no significant differences in NOM between subjects with HFrEF and subjects without HF (P=1.00). In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure and glomerular filtration rate, HFpEF remained an independent predictor of lower NOM (β=-0.43; P=0.013). NOM did not correlate with LV mass, or LV diffuse fibrosis. In conclusion. HFpEF, but not HFrEF, is associated with reduced plasma NOM, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.
Author Disclosures: J.A. Chirinos: Research Grant; Significant; NIH, American College of Radiology Network, Fukuda Denshi, Bristol Myers Squibb, Microsoft and CVRx Inc. Other Research Support; Modest; Fukuda Denshi, Withings, Atcor Medical. Consultant/Advisory Board; Modest; Fukuda Denshi, Microsoft Research, Merck and Vital Labs. Consultant/Advisory Board; Significant; Bristol Myers Squibb, OPKO Healthcare. S.R. Akers: None. L. Trieu: None. H. Ischiropoulos: None. P. Doulias: None. A. Tariq: None. I. Vassim: None. M.R. Koppula: None. A. Syed: None. H. Soto-Calderon: None. R.R. Townsend: Consultant/Advisory Board; Modest; Medtronic, Fukuda Denshi, Relypsa. Consultant/Advisory Board; Significant; Medtronic, Fukuda Denshi, Relypsa. T.P. Cappola: Other Research Support; Modest; BG medicine, Abbott Diagnostics. K.B. Margulies: Research Grant; Modest; uventis 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. P. Zamani: None.
- © 2016 by American Heart Association, Inc.