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FOCUS ISSUE: BIOMARKERS IN CARDIOVASCULAR DISEASE: CLINICAL RESEARCH: BIOMARKERS IN HEART FAILURE

The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects

Paul M. McKie, MD^_*,,_*, Alessandro Cataliotti, MD, PhD^_*, Brian D. Lahr, MS, Fernando L. Martin, MD^_*, Margaret M. Redfield, MD^_*,, Kent R. Bailey, PhD, Richard J. Rodeheffer, MD and John C. Burnett, Jr, MD^_*,

^_* Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota
Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
Department of Biostatistics, Mayo Clinic and Foundation, Rochester, Minnesota

Manuscript received July 15, 2009; revised manuscript received December 4, 2009, accepted January 11, 2010.

^_* Reprint requests and correspondence: Dr. Paul M. McKie, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (Email: mckie.paul{at}mayo.edu).

Objectives: Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal.

Background: Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects.

Methods: We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively.

Results: NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities.

Conclusions: These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP–based strategies for early detection and primary prevention of cardiovascular disease.

Key Words: natriuretic peptide • predictive • mortality • heart failure • myocardial infarction • cerebrovascular accident

Abbreviations and Acronyms   BMI = body mass index   BNP = B-type natriuretic peptide   CAD = coronary artery disease   CVA = cerebrovascular accident   HF = heart failure   IDI = integrated discrimination improvement   NT-proBNP = N-terminal pro-B-type natriuretic peptide

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