Article Text

Download PDFPDF
Diversity of molecular forms of plasma brain natriuretic peptide in heart failure—different proBNP-108 to BNP-32 ratios in atrial and ventricular overload
  1. T Nishikimi1,
  2. N Minamino2,
  3. M Ikeda3,
  4. Y Takeda1,
  5. K Tadokoro1,
  6. I Shibasaki4,
  7. H Fukuda4,
  8. Y Horiuchi5,
  9. S Oikawa5,
  10. T Ieiri5,
  11. M Matsubara2,
  12. T Ishimitsu1
  1. 1Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Tochigi, Japan
  2. 2Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan
  3. 3Institute of International Education and Research, Dokkyo Medical University, Tochigi, Japan
  4. 4Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan
  5. 5Department of Clinical Laboratory, Dokkyo Medical University, Tochigi, Japan
  1. Correspondence to Professor Toshio Nishikimi, Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan; nishikim{at}


Objective Recent studies have shown that plasma levels of brain natriuretic peptide (BNP)-32 and proBNP-108 are increased in heart failure (HF) and that the BNP-32 assay kit in current clinical use cross-reacts with proBNP-108. We investigated why proBNP is increased without processing in HF was investigated.

Design, setting and patients Plasma BNP-32 and proBNP-108 in normal individuals (n=10) and in patients with atrial fibrillation (AF) (n=18) and HF (n=132) was measured. BNP-32 and proBNP-108 in ventricular and atrial tissue and in pericardial fluid using a specific fluorescent enzyme immunoassay following Sep-Pak C18 (Waters, Milford, Massachusetts, USA) cartridge extraction and gel filtration was also measured.

Main outcome measures Levels of both BNP-32 and proBNP-108 were higher in HF than in control or AF (both p<0.01), and the levels of these peptides significantly correlated (r=0.94, p<0.001). The proBNP-108/total BNP (BNP-32+proBNP-108) ratio was widely distributed and lower in HF (0.33 (0.17)) than in control (0.41 (0.06), p<0.05) and AF (0.45 (0.04), p<0.002). The proBNP-108/total BNP ratio was higher in HF with ventricular than in HF with atrial overload (0.45 (0.10) vs 0.20 (0.11), p<0.001). Consistent with this finding, the major molecular form were proBNP-108 and BNP-32 in ventricular (n=6, 0.67 (0.04)) and atrial (n=7, 0.76 (0.05), p<0.0001) tissues, respectively. ProBNP-108 was also the major molecular form of BNP in pericardial fluid (n=8, 0.82 (0.05)). The proBNP-108/total BNP ratio increased and decreased with HF deterioration and improvement, respectively.

Conclusion These results suggest that BNP-32 and proBNP-108 is increased in HF and that the proBNP/total BNP ratio increases in association with pathophysiological conditions such as ventricular overload.

  • Brain natriuretic peptide
  • heart failure
  • molecular form
  • atrial overload
  • ventricular overload
  • endocrinology
  • aortic valve disease
  • mitral regurgitation
  • mitral stenosis

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding This work was supported in part by Scientific Research Grants-in-Aid (nos. 14570692, 18590787 and 20590837) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan and by a Research Grant for Cardiovascular Diseases “20C-3” from the Ministry of Health, Labour and Welfare of Japan.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Dokkyo Medical University.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.