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CLINICAL RESEARCH

Alternate Circulating Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide Forms in the General Population

Carolyn S.P. Lam, MBBS, MRCP^_*,, John C. Burnett, Jr, MD^_*, Lisa Costello-Boerrigter, MD, PhD^_*, Richard J. Rodeheffer, MD, FACC^_* and Margaret M. Redfield, MD, FACC^_*,_*

^_* Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
Yong Loo Lin School of Medicine, National University of Singapore, Singapore Singapore

Manuscript received July 10, 2006; revised manuscript received October 31, 2006, accepted November 2, 2006.

^_* Reprint requests and correspondence: Dr. Margaret M. Redfield, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905. (Email: redfield.margaret{at}mayo.edu).

Objectives: This study was designed to determine whether alternate pro-B-type natriuretic peptide (proBNP) and BNP forms circulate in the general population.

Background: Bioactive BNP_1-32 and NT-proBNP_1-76 are derived from a precursor molecule, proBNP_1-108. Recent data suggest that aminodipeptidase-processed forms of BNP_1-32 (BNP_3-32) and of proBNP_1-108 itself (proBNP_3-108) may circulate and have additional diagnostic potential.

Methods: Residents (age 45 years) of Olmsted County, Minnesota, underwent medical review, echocardiography, and phlebotomy for 2 novel assays specific for proBNP_3-108 and BNP_3-32 and 2 commercial assays (Triage BNP and Roche NT-proBNP). Groups included normal subjects (n = 613), cardiovascular disease with normal ventricular function (n = 1,043), preclinical ventricular dysfunction (ALVD, n = 130), and chronic heart failure (HF, n = 52).

Results: ProBNP_3-108 levels were above assay detection limits in 68% of normal subjects (50th; 25th to 75th percentiles: 7.85; 3.00 to 22.45 pmol/l) and correlated with age, gender, body size, and renal function and with results of commercial assays. ProBNP_3-108 levels were higher in ALVD (17.88; 6.07 to 42.76 pmol/l) or HF (42.75; 20.51 to 65.73 pmol/l), where they correlated more strongly with commercial assays. BNP_3-32 was above assay detection limits in 22% of normal subjects; levels were not correlated with age, body size, or renal function but were higher in HF. Neither novel assay was superior to commercial assays for the detection of ALVD or HF.

Conclusions: The presence of alternate circulating proBNP and BNP forms provides evidence for diverse proBNP and BNP processing in the general population. The physiologic consequences of these observations, both in terms of assay performance and endogenous BNP bioactivity, deserve further study.

Abbreviations and Acronyms   aa = amino acid   ALVD = asymptomatic left ventricular dysfunction   BNP = B-type natriuretic peptide   BSA = body surface area   CV = cardiovascular   EF = ejection fraction   GFR = glomerular filtration rate   HF = heart failure   MDC = minimal detectable concentration   NT = N-terminal   ROC = receiver operating characteristic

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