Biological Variation of Natriuretic Peptides and Other Cardiovascular Disease-Related Biomarkers: A Systematic Review and Meta-analysis

TY - JOUR

T1 - Biological Variation of Natriuretic Peptides and Other Cardiovascular Disease-Related Biomarkers

T2 - A Systematic Review and Meta-analysis

AU - Fernández-Calle, Pilar

AU - Díaz-Garzón, Jorge

AU - Bartlett, Bill

AU - Coskun, Abdurrahman

AU - Carobene, Anna

AU - González-Lao, Elisabeth

AU - Marqués-García, Fernando

AU - Sufrate-Vergara, Berta

AU - Moreno-Parro, Isabel

AU - Galior, Kornelia

AU - Topcu, Denis İlhan

AU - Sandberg, Sverre

AU - Aarsand, Aasne K.

N1 - Publisher Copyright: © Association for Diagnostics & Laboratory Medicine 2026. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

PY - 2026/8

Y1 - 2026/8

N2 - Background: The clinical application of cardiovascular disease (CVD) biomarkers requires robust biological variation (BV) data to enable both interpretation of serial results and definition of appropriate analytical quality. A critical review and meta-analysis of eligible BV studies of natriuretic peptides and other CVD-related biomarkers was therefore undertaken, with a focus on differences observed in different states of health and the impact of sampling intervals on BV. Methods: BV studies of N-terminal pro–B-type natriuretic peptide (NT-proBNP), brain natriuretic peptide, N-terminal pro–A-type natriuretic peptide, galectin, copeptin, soluble suppression of tumorigenicity-2, and growth differentiation factor 15 were identified by a systematic literature review and assessed using the Biological Variation Data Critical Appraisal Checklist. A meta-analysis of eligible studies was used to derive within-subject (CVI) and between-subject BV estimates, which were used to calculate analytical performance specifications, indices of individuality, and reference change values. Results: Twenty-one studies were identified, only 3 of which achieved an A grade on the Biological Variation Data Critical Appraisal Checklist, indicating full checklist compliance. For NT-proBNP, meta-analysis–derived CVI estimates depended on sampling frequencies and study duration: <15 days (9.9%; 95% CI, 8.8–18.0) and >15 days (34.3%; 95% CI, 25.0–60.0). For the other biomarkers, from one to 5 BV studies were identified, reporting on different states of health and sampling intervals. Conclusions: This systematic review provides quality-assessed BV data for natriuretic peptides and other CVD markers. Our results highlight the influence of sampling frequency on CVI for NT-proBNP, potentially impacting the intended use. Further BV studies applicable to multiple clinical scenarios are required.

AB - Background: The clinical application of cardiovascular disease (CVD) biomarkers requires robust biological variation (BV) data to enable both interpretation of serial results and definition of appropriate analytical quality. A critical review and meta-analysis of eligible BV studies of natriuretic peptides and other CVD-related biomarkers was therefore undertaken, with a focus on differences observed in different states of health and the impact of sampling intervals on BV. Methods: BV studies of N-terminal pro–B-type natriuretic peptide (NT-proBNP), brain natriuretic peptide, N-terminal pro–A-type natriuretic peptide, galectin, copeptin, soluble suppression of tumorigenicity-2, and growth differentiation factor 15 were identified by a systematic literature review and assessed using the Biological Variation Data Critical Appraisal Checklist. A meta-analysis of eligible studies was used to derive within-subject (CVI) and between-subject BV estimates, which were used to calculate analytical performance specifications, indices of individuality, and reference change values. Results: Twenty-one studies were identified, only 3 of which achieved an A grade on the Biological Variation Data Critical Appraisal Checklist, indicating full checklist compliance. For NT-proBNP, meta-analysis–derived CVI estimates depended on sampling frequencies and study duration: <15 days (9.9%; 95% CI, 8.8–18.0) and >15 days (34.3%; 95% CI, 25.0–60.0). For the other biomarkers, from one to 5 BV studies were identified, reporting on different states of health and sampling intervals. Conclusions: This systematic review provides quality-assessed BV data for natriuretic peptides and other CVD markers. Our results highlight the influence of sampling frequency on CVI for NT-proBNP, potentially impacting the intended use. Further BV studies applicable to multiple clinical scenarios are required.

UR - https://www.scopus.com/pages/publications/105046289937

U2 - 10.1093/clinchem/hvag051

DO - 10.1093/clinchem/hvag051

M3 - Article

C2 - 42275244

AN - SCOPUS:105046289937

SN - 0009-9147

VL - 72

SP - 857

EP - 867

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 8

ER -