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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Serum Blood Urea Nitrogen as an Independent Marker of Subsequent Mortality Among Patients With Acute Coronary Syndromes and Normal to Mildly Reduced Glomerular Filtration Rates

Ajay J. Kirtane, MD^_*, David M. Leder, MD^_*, Sushrut S. Waikar, MD, Glenn M. Chertow, MD, MPH, Kausik K. Ray, MRCP, MD, Duane S. Pinto, MD^_*, Dimitrios Karmpaliotis, MD^_*, Andrew J. Burger, MD^_*, Sabina A. Murphy, MPH, Christopher P. Cannon, MD, Eugene Braunwald, MD, C. Michael Gibson, MS, MD^_*,_* for the TIMI Study Group

^_* Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Department of Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Department of Medicine, University of California, San Francisco, San Francisco, California

Manuscript received December 20, 2004; revised manuscript received February 8, 2005, accepted February 14, 2005.

^_* Reprint requests and correspondence: Dr. C. Michael Gibson, 350 Longwood Avenue, First Floor, Boston, Massachusetts 02115. (Email: mgibson{at}perfuse.org).

OBJECTIVES: We hypothesized that elevated blood urea nitrogen (BUN) would be associated with adverse outcomes independent of serum creatinine (sCr)-based estimates of kidney function in patients with acute coronary syndromes (ACS).

BACKGROUND: Although lower glomerular filtration rates (GFR) have prognostic significance among patients with ACS, estimates of GFR based on sCr may perform less accurately among patients with milder kidney dysfunction. In this population in particular, BUN, which can reflect increased proximal tubular reabsorption in addition to decreased GFR, may have independent prognostic value.

METHODS: Data were drawn from 9,420 patients with unstable coronary syndromes from Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI)-16, a trial that excluded patients with sCr >1.6 mg/dl or estimated creatinine clearance <40 ml/min.

RESULTS: Patients with elevated BUN were older, had a higher prevalence of comorbidities, and had higher heart rates, lower systolic blood pressures, and an abnormal Killip class more often on admission. In univariate analyses, as well as in stratified and multivariable analyses including sCr-based estimates of GFR as a covariate, a stepwise increase in mortality occurred with increasing BUN (multivariable hazard ratio with BUN 20 to 25 mg/dl 1.9, 95% confidence interval 1.3 to 2.6; with BUN 25 mg/dl 3.2 [95% confidence interval 2.2 to 4.7]) compared with BUN 20 mg/dl. A higher BUN was also associated with increased mortality among strata of troponin-I, B-type natriuretic peptide, and C-reactive protein concentrations.

CONCLUSIONS: Among patients with unstable coronary syndromes and predominantly normal or mildly reduced GFR, an elevated BUN is associated with increased mortality, independent of sCr-based estimates of GFR and other biomarkers.

Abbreviations and Acronyms   ACS = acute coronary syndromes   BNP = B-type natriuretic peptide   BUN = blood urea nitrogen   CKD = chronic kidney disease   CRP = C-reactive protein   eCrCl = estimated creatinine clearance   eGFR = estimated glomerular filtration rate   GFR = glomerular filtration rate   OPUS-TIMI-16 = Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction-16 trial   sCr = serum creatinine

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