Correspondence

N-Terminal Pro–B-Type Natriuretic Peptide and Mortality in Coronary Heart Disease

N Engl J Med 2005; 352:2025-2026May 12, 2005

Article

To the Editor:

Kragelund and colleagues (Feb. 17 issue)1 tested the N-terminal fragment of pro–brain natriuretic peptide (NT-pro-BNP) as a marker of long-term mortality in patients with stable coronary disease and concluded that it provides improved prognostic information as compared with conventional cardiovascular risk factors. Creatinine clearance was not found to be a significant risk factor. However, the effect of renal function should be clarified in more detail, since moderate renal impairment is well established as a strong predictor of cardiovascular disease and mortality from all causes,2 and since NT-pro-BNP is primarily eliminated by the kidneys.3,4 Increased NT-pro-BNP levels may reflect diminished renal function, left ventricular wall stress, or both.5 Thus, it might be of considerable interest to perform a Kaplan–Meier survival analysis according to quartiles of creatinine clearance and to test the hazard ratios for death with creatinine clearance (fourth vs. first quartile) as the variable for the multivariate analysis. Since the relation between the two predictors — renal function and NT-pro-BNP — is intricate and hampers interpretation of the results, this additional information would facilitate a better understanding of the data.

Uwe Pöge, M.D.
Thomas M. Gerhardt, M.D.
Rainer P. Woitas, M.D.
Universitätsklinikum Bonn, 53127 Bonn, Germany
woitas@uni-bonn.de

5 References

1. 1

   Kragelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R. NT-pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 2005;352:666-675
   Full Text | Web of Science | Medline

2. 2

   Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307-1315
   CrossRef | Web of Science | Medline

3. 3

   Cameron SJ, Green GB. Cardiac biomarkers in renal disease: the fog is slowly lifting. Clin Chem 2004;50:2233-2235
   CrossRef | Web of Science | Medline

4. 4

   Apple FS, Murakami MM, Pearce LA, Herzog CA. Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all-cause death. Clin Chem 2004;50:2279-2285
   CrossRef | Web of Science | Medline

5. 5

   McCullough PA, Sandberg KR. B-type natriuretic peptide and renal disease. Heart Fail Rev 2003;8:355-358
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Pöge and colleagues argue that the effect of renal function on mortality should be clarified in more detail. We agree that moderate renal impairment is a well-established risk factor for mortality.1 However, our study included few patients with renal impairment. The clearance mechanisms for NT-pro-BNP are not yet known, and whether increased NT-pro-BNP in patients with impaired renal function is due to volume overload, intrinsic heart disease, decreased renal clearance, or a combination of the three is unknown.2 Although natriuretic peptides and N-terminal prohormone fragments can be identified and measured in urine, levels are very low, suggesting that renal filtration is not a major pathway for natriuretic peptide degradation.3 We found a negative correlation between creatinine clearance and NT-pro-BNP (Spearman's rho = –0.34, P<0.001). Entering creatinine clearance in the multivariable models as either a continuous variable or a categorical variable in quartiles did not change the results. Similarly, there was no relation between the effects of NT-pro-BNP and creatinine clearance on mortality.

Charlotte Kragelund, M.D.
Frederiksberg University Hospital, DK-2000 Frederiksberg, Denmark
kragelund@dadlnet.dk

Lars Køber, D.M.Sc.
Rigshospitalet, DK-2100 Copenhagen, Denmark

Per Hildebrandt, D.M.Sc.
Frederiksberg University Hospital, DK-2000 Frederiksberg, Denmark

3 References

1. 1

   Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004;351:1285-1295
   Full Text | Web of Science | Medline

2. 2

   Apple FS, Panteghini M, Ravkilde J, et al. Quality specifications for B-type natriuretic peptide assays. Clin Chem 2005;51:486-493
   CrossRef | Web of Science | Medline

3. 3

   McCullough PA, Sandberg KR. B-type natriuretic peptide and renal disease. Heart Fail Rev 2003;8:355-358
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   W.H. Wilson Tang, Gary S. Francis, David A. Morrow, L. Kristin Newby, Christopher P. Cannon, Robert L. Jesse, Alan B. Storrow, Robert H. Christenson, Robert H. Christenson, Fred S. Apple, Christopher P. Cannon, Gary S. Francis, Robert L. Jesse, David A. Morrow, L. Kristin Newby, Alan B. Storrow, W. H. Wilson Tang, Alan H.B. Wu. (2008) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure. Clinical Biochemistry 41:4-5, 210-221
   CrossRef

2. 2

   W.H. Wilson Tang, Steven R. Steinhubl, Frederick Van Lente, Danielle Brennan, Ellen McErlean, Anjli Maroo, Gary S. Francis, Eric J. Topol. (2007) Risk stratification for patients undergoing nonurgent percutaneous coronary intervention using N-terminal pro–B-type natriuretic peptide: A Clopidogrel for the Reduction of Events During Observation (CREDO) substudy. American Heart Journal 153:1, 36-41
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