title: Relation of serum uric acid levels and outcomes among patients hospitalized for worsening heart failure with reduced ejection fraction (from the efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan trial).
abstract: We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) ≤40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles. The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 ± 2.8 mg/dl and was higher in men than in women (9.3 ± 2.7 vs 8.7 ± 3.0 mg/dl, p <0.001) and in blacks than in whites (10.0 ± 2.7 vs 9.0 ± 2.8 mg/dl, p <0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate ≥30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: muthu@md.northwestern.edu.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Ambrosy
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mentz
authors.affiliation: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Haris P
authors.initials: HP
authors.lastname: Subacius
authors.affiliation: Institute of Emergency for Cardiovascular Diseases "Prof. C.C. Iliescu", Cardiology, Bucharest, Romania.
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Chioncel
authors.affiliation: Research Center of the Italian Association of Hospital Cardiologists (ANMCO), Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Department of Cardiology, Nancy University, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.affiliation: Dipartimento Cardiovascolare, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Senni
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D001741:Black or African American; D000367:Age Factors; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors; D013318:Stroke Volume; D013599:Systole; D000077602:Tolvaptan; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D044465:White People
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D045265:Natriuretic Peptides; D000077602:Tolvaptan; D014527:Uric Acid