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

Background: 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. Methods: Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65 +/- 7 years) and 18 healthy control subjects (44% men, 57 +/- 7 years). 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). Results: Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, 5ICAM-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 5CD4OL in PAD patients. Conclusions: 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, PAL-I, sP-selectin and 5ICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies. (C) 2015 Elsevier B.V. All rights reserved.