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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Volume 56, Issue 1


Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose

Peter D. Mark / Ingrid Hunter / Dijana Terzic / Jens P. Goetze
Published Online: 2017-07-08 | DOI: https://doi.org/10.1515/cclm-2017-0309



Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively.


We report an optimized processing-independent assay (PIA) for proANP in the lower concentration range. The assay was optimized by raising the amount of radioactive tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood samples from a Scandinavian plasma cohort of 693 healthy subjects were then analyzed and age and gender-specific reference intervals were determined.


Simple linear regression analyses of proANP and both BMI and plasma glucose in fasting subjects displayed insignificant associations. Multiple regression analyses supported these findings. However, a higher median plasma concentration of proANP was noted among women <50 years compared to men, whereas no gender-specific differences were seen in other age groups.


Our results show that in a healthy non-obese population, BMI and plasma glucose in fasting subjects do not affect plasma proANP concentrations. Our method should be considered for future studies on low proANP concentration studies, e.g. in obesity and diabetes.

Keywords: atrial natriuretic peptide; body mass index; natriuretic peptides; pro-atrial natriuretic peptide; processing-independent assay; reference intervals


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About the article

Corresponding author: Jens P. Goetze, MD, DMSc, Professor, Chief Physician, Department of Clinical Biochemistry (KB3014), Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark, Phone: +45-3545-2202, Fax: +45-3545-2880

Received: 2017-04-08

Accepted: 2017-05-12

Published Online: 2017-07-08

Published in Print: 2017-11-27

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: An unrestricted research grant from the Novo Nordisk Foundation.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages 132–137, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0309.

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