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

Abstract 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.