Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.

Engelberger, Rolf P; Limacher, Andreas; Kucher, Nils; Baumann, Frédéric; Silbernagel, Günther; Benghozi, Renée; Do, Dai-Do; Willenberg, Torsten Andreas; Baumgartner, Iris (2015). Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study. Clinica chimica acta, 447, pp. 16-22. Elsevier 10.1016/j.cca.2015.05.003

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Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies.


Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC).


Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients.


Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Angiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)

UniBE Contributor:

Engelberger, Rolf Peter, Limacher, Andreas, Kucher, Nils, Baumann, Frederic, Silbernagel, Günther, Do, Dai-Do, Willenberg, Torsten Andreas, Baumgartner, Iris


600 Technology > 610 Medicine & health








Doris Kopp Heim

Date Deposited:

27 May 2015 09:46

Last Modified:

20 Feb 2024 14:17

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Atherosclerosis; Biological variation; Biomarkers; Inflammation; Peripheral vascular disease




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