{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:55:01Z","timestamp":1790470501560,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,10,3]]},"abstract":"\n Background<\/jats:title>\n \n Stable plasma nitric oxide (\n NO<\/jats:styled-content>\n ) metabolites (\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n ), composed predominantly of nitrate and nitrite, are attractive biomarkers of\n NO<\/jats:styled-content>\n bioavailability.\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n levels integrate the influence of\n NO<\/jats:styled-content>\n \u2010synthase\u2010derived\n NO<\/jats:styled-content>\n production\/metabolism, dietary intake of inorganic nitrate\/nitrite, and clearance of\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n . Furthermore, nitrate and nitrite, the most abundant\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n , can be reduced to\n NO<\/jats:styled-content>\n via the nitrate\u2010nitrite\u2010\n NO<\/jats:styled-content>\n pathway.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We compared serum\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n ; n=43), and subjects with heart failure and reduced ejection fraction (\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n ; n=32).\n LV<\/jats:styled-content>\n mass and extracellular volume fraction were measured with cardiac\n MRI<\/jats:styled-content>\n . Plasma\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n levels were measured after reduction to\n NO<\/jats:styled-content>\n via reaction with vanadium (\n III<\/jats:styled-content>\n )\/hydrochloric acid. Subjects with\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n demonstrated significantly lower unadjusted levels of\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n (8.0\u00a0\u03bcmol\/L; 95%\n CI<\/jats:styled-content>\n 6.2\u201310.4\u00a0\u03bcmol\/L;\n ANOVA<\/jats:styled-content>\n P<\/jats:italic>\n =0.013) than subjects without\n HF<\/jats:styled-content>\n (12.0\u00a0\u03bcmol\/L; 95%\n CI<\/jats:styled-content>\n 10.4\u201313.9\u00a0\u03bcmol\/L) or those with\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n (13.5\u00a0\u03bcmol\/L; 95%\n CI<\/jats:styled-content>\n 9.7\u201318.9\u00a0\u03bcmol\/L). There were no significant differences in\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n between subjects with\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n and subjects without\n HF<\/jats:styled-content>\n . In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate,\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n remained a predictor of lower\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n (\u03b2=\u22120.43;\n P<\/jats:italic>\n =0.013).\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n did not correlate with\n LV<\/jats:styled-content>\n mass, or\n LV<\/jats:styled-content>\n diffuse fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n , but not\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n , is associated with reduced plasma\n \n NO\n M<\/jats:sub>\n <\/jats:styled-content>\n , 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\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.004133","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T21:59:41Z","timestamp":1476482381000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites"],"prefix":"10.1161","volume":"5","author":[{"given":"Julio A.","family":"Chirinos","sequence":"first","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"},{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Akers","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"Trieu","sequence":"additional","affiliation":[{"name":"Rowan University School of Osteopathic Medicine, Stratford, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Ischiropoulos","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"},{"name":"Children's Hospital of Philadelphia Research Institute, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paschalis\u2010Thomas","family":"Doulias","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"},{"name":"Children's Hospital of Philadelphia Research Institute, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tariq","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izzah","family":"Vasim","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maheswara R.","family":"Koppula","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer Ahmed","family":"Syed","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haideliza","family":"Soto\u2010Calderon","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond R.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Cappola","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Margulies","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VAMC, Philadelphia, PA"},{"name":"University of Pennsylvania School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payman","family":"Zamani","sequence":"additional","affiliation":[{"name":"Corporal Michael J. 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