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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.

ABSTRACT: 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.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.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.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.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.

SUBMITTER: McKie PM

PROVIDER: S-EPMC3770189 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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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.

McKie Paul M PM Cataliotti Alessandro A Lahr Brian D BD Martin Fernando L FL Redfield Margaret M MM Bailey Kent R KR Rodeheffer Richard J RJ Burnett John C JC

Journal of the American College of Cardiology 20100501 19

<h4>Objectives</h4>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.<h4>Background</h4>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 subje ...[more]

PMID: 20447539

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Project description:BACKGROUND:B-type natriuretic peptide (BNP), a key cardiac hormone in cardiorenal homeostasis, is produced as a 108 amino acid prohormone, proBNP1-108, which is converted to a biologically active peptide BNP1-32 and an inactive N-terminal (NT)-proBNP1-76. The widely accepted model is that the normal heart releases a proteolytically processed BNP1-32 and NT-proBNP, whereas the diseased heart secretes high amounts of unprocessed/glycosylated proBNP1-108 or inappropriately processed BNPs. In contrast, circulating proBNP1-108 has recently been identified in healthy individuals, indicating that the normal heart also secretes unprocessed proBNP1-108. However, the mechanism of proBNP1-108 secretion from the normal heart remains elusive. Our goal was to determine the molecular mechanisms underlying proBNP1-108 intracellular trafficking and secretion from the normal heart. METHODS:We expressed preproBNP in cardiomyocytes, and determined the subcellular localization and dominant intracellular and extracellular forms of BNP. RESULTS:Intracellular immunoreactive BNPs were first accumulated in the Golgi apparatus, and then distributed throughout the cytoplasm as secretory vesicles. The predominant intracellular form of BNP was nonglycosylated proBNP1-108, rather than BNP1-32. Glycosylated proBNP1-108, but not nonglycosylated proBNP1-108, was detected as the major extracellular form in the culture supernatants of preproBNP-expressing cell lines and primary human cardiomyocytes. Ablation of O-glycosylation of proBNP1-108 at T71 residue, near the convertase recognition site, reduced the extracellular proBNP1-108 and increased extracellular BNP1-32. CONCLUSIONS:Intracellular proBNP trafficking occurs through a conventional Golgi-endoplasmic reticulum pathway. Glycosylation of proBNP1-108 controls the stability and processing of extracellular proBNP1-108. Our data establish a new BNP secretion model in which the normal cardiac cells secrete glycosylated proBNP1-108.

Dataset Information

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.

Publications

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.

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