High variability in assays of blood markers of collagen turnover in cardiovascular disease: Implications for research and clinical practice

Author:

Rubiś Pawel Piotr1,Dziewięcka Ewa1,González Arantxa23,Cleland John G.F.4

Affiliation:

1. Krakow Specialist Hospital named after St. John Paul II, Department of Cardiac and Vascular Diseases Jagiellonian University Medical College Krakow Poland

2. Program of Cardiovascular Disease, CIMA Universidad de Navarra, Department of Pathology, Anatomy and Physiology Universidad de Navarra and IdiSNA Pamplona Spain

3. CIBERCV, Carlos III Institute of Health Madrid Spain

4. British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Health University of Glasgow Glasgow UK

Abstract

AbstractAimsFibrosis is a common feature of many chronic diseases, including heart failure, which can have deleterious effects on cardiac structure and function that are associated with adverse outcomes. By‐products of collagen synthesis and degradation, such as carboxy‐ and amino‐terminal pro‐ or telo‐peptides of collagen type I and III (PICP, PINP, PIIINP, and CITP) have been extensively investigated as markers of fibrosis. Although the majority of studies report on the reproducibility of their assay results, there is no a comparison of biomarker assays across studies. Therefore, we conducted a systematic review adhering to PRISMA guidelines.Methods and resultsThe search terms employed in Medline were: ‘collagen AND cardiac’ or ‘collagen AND heart’. This query yielded a total of 1049 articles. Thereafter, specific search criteria were applied: (i) original English‐language papers; (ii) human studies; (iii) in‐vivo investigations; and (iv) blood/serum/plasma samples. Overall, 89 studies were identified (42 on PIIINP, 32 on PICP, 29 on CITP, and 17 on PINP). The range of reported values for PIIINP was between 0.06 to 11 800 μg/l; for PICP 0.006 to 1265 μg/l; for CITP 0.3 to 5450 μg/l; for PINP 0.15 to 80 μg/l. Extreme variations in values for fibrosis biomarkers were observed across studies, especially when different assays were used, but also with the same assays.ConclusionsOur findings show that it is challenging to ascertain normal ranges or compare studies for the measurement of fibrosis biomarkers. Given the potential implications for clinical practice and current lack of awareness of these issues, this subject warrants comprehensive acknowledgement and understanding.

Funder

Narodowe Centrum Nauki

European Regional Development Fund

Publisher

Wiley

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