Lam Carolyn S P, Burnett John C, Costello-Boerrigter Lisa, Rodeheffer Richard J, Redfield Margaret M
Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
J Am Coll Cardiol. 2007 Mar 20;49(11):1193-202. doi: 10.1016/j.jacc.2006.12.024. Epub 2007 Mar 6.
This study was designed to determine whether alternate pro-B-type natriuretic peptide (proBNP) and BNP forms circulate in the general population.
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.
Residents (age > or =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).
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.
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.
本研究旨在确定在普通人群中是否存在交替的B型利钠肽原（proBNP）和B型利钠肽（BNP）形式。
生物活性BNP（1-32）和N末端B型利钠肽原（NT-proBNP，1-76）来源于前体分子proBNP（1-108）。最近的数据表明，经氨基二肽酶处理的BNP（1-32）形式（BNP（3-32））和proBNP（1-108）本身的形式（proBNP（3-108））可能在血液循环中存在，并具有额外的诊断潜力。
明尼苏达州奥尔姆斯特德县的居民（年龄≥45岁）接受了医学检查、超声心动图检查和静脉穿刺，以进行两种针对proBNP（3-108）和BNP（3-32）的新型检测以及两种商业检测（Triage BNP和罗氏NT-proBNP）。研究组包括正常受试者（n = 613）、心室功能正常的心血管疾病患者（n = 1043）、临床前期心室功能障碍患者（无症状左心室功能障碍，ALVD，n = 130）和慢性心力衰竭患者（HF，n = 52）。
在68%的正常受试者中，proBNP（3-108）水平高于检测限（第50百分位数；第25至75百分位数：7.85；3.00至22.45 pmol/L），并且与年龄、性别、体型、肾功能以及商业检测结果相关。在无症状左心室功能障碍（17.88；6.07至42.76 pmol/L）或心力衰竭（42.75；20.51至65.73 pmol/L）患者中，proBNP（3-108）水平更高，并且与商业检测结果的相关性更强。在22%的正常受试者中，BNP（3-32）高于检测限；其水平与年龄、体型或肾功能无关，但在心力衰竭患者中更高。对于无症状左心室功能障碍或心力衰竭的检测，这两种新型检测均不优于商业检测。
交替循环的proBNP和BNP形式的存在为普通人群中proBNP和BNP的多样化加工提供了证据。这些观察结果在检测性能和内源性BNP生物活性方面的生理后果值得进一步研究。
