Clin Chem Lab Med 2007;45(10):1339–1346  2007 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2007.279 2007/153 Article in press - uncorrected proof Association of classical and related inflammatory markers with high-sensitivity C-reactive protein in healthy individuals: results from the Stanislas cohort Hind Berrahmoune 1 , Bernard Herbeth 1 , John V. Lamont 2 , Daniel Lambert 1 , Stefan Blankenberg 3 , Laurence Tiret 4 , Peter S. FitzGerald 2 , Ge ´ rard Siest 1,5 and Sophie Visvikis-Siest 1, * 1 INSERM, U525, e ´ quipe 4, Nancy, France 2 Randox Laboratories Ltd., Crumlin, Antrim, UK 3 Department of Medicine II, Johannes Gutenberg- University Mainz, Mainz, Germany 4 INSERM, U525, Paris, France 5 Universite ´ Henry Poincare ´ – Nancy I, Faculte ´ de Pharmacie, Nancy, France Abstract Background: Although high-sensitivity C-reactive pro- tein (hs-CRP) has emerged as a cardiovascular mark- er, questions arise regarding the relative information provided by other inflammatory molecules. There- fore, as a first step, we examined interrelationships between serum hs-CRP concentrations and inflam- matory, adhesion and growth factors in healthy adults. Methods: Circulating concentrations of hs-CRP, haptoglobin, orosomucoid, interleukin-6 (IL-6), IL-8, IL-18, tumor necrosis factor-a (TNF-a), TNF-receptor II (TNF-RII), E-, P-, and L-selectins, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant pro- tein-1, endothelial growth factor (EGF), vascular EGF (VEGF), insulin-like growth factor-1 (IGF-1) and IGF- binding protein (IGFBP-3) were measured in 154 men and 161 women of the Stanislas cohort. Leukocyte and platelet counts were also determined. Results: Correlations were significant between hs- CRP concentrations and leukocyte and platelet counts, as well as haptoglobin, orosomucoid, IL-6, and ICAM- 1 concentrations (pF0.001). Correlation coefficients for ICAM-1 were higher in men than in women (pF0.05). When stratifying subjects according to hs- CRP levels, the group with high hs-CRP levels had significantly higher haptoglobin and orosomucoid concentrations than the others, in addition to higher leukocyte counts and IL-6 concentrations in women, and platelet counts and ICAM-1 concentrations in men. Conclusions: Further studies are warranted to explain the association pattern for hs-CRP. Partition of these factors according to their association with hs-CRP *Corresponding author: Dr. Sophie Visvikis-Siest, INSERM U525, 30 rue Lionnois, 54000 Nancy, France Phone: q33-3-83682184, Fax: q33-3-83321322, E-mail: sophie.visvikis-siest@nancy.insem.fr concentration opens a new perspective for choice of the best factors in terms of cardiovascular risk in rela- tion to hs-CRP, while non-associated markers could be used to give additional information. Clin Chem Lab Med 2007;45:1339–46. Keywords: atherosclerosis; cellular adhesion; growth factors; high-sensitivity C-reactive protein; inflamma- tion. Introduction Over the past decade, we have come to appreciate the prominent role of inflammation in atherosclerosis and its complications (1). This led to a rush to identify can- didate inflammatory markers of cardiovascular dis- ease (CVD) and risk. To date, high-sensitivity C-reactive protein (hs- CRP), an inflammatory acute-phase reactant, seems to be the most consistent inflammatory biomarker for the risk of CVD in a variety of clinical settings (2). Indeed, it has been shown in prospective cohort and case-control studies to be a reliable measure of underlying systemic inflammation and a strong pre- dictor of future CVD events, stimulating interest in a possible role for hs-CRP measurement in CVD risk assessment in clinical practice (3–6). These results and others led the Centers for Disease Control and Prevention (CDCP) and the American Heart Associa- tion (AHA) to recommend in 2003 the use of hs-CRP as an inflammatory marker in clinical and public health practice (7). However, Danesh et al. (8) con- cluded from a meta-analysis that CRP is a relatively moderate predictor of coronary heart disease, and thus recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed. In addition, high hs-CRP levels indicate a low-grade chronic inflammation, implying the involvement of several intermediate phenotypes (cells and other quantities) that may also be interest- ing markers of CVD risk. Therefore, many questions arise, in particular: Is hs- CRP the best inflammatory marker in terms of CVD? And is hs-CRP the only inflammatory marker to be used in this field? To answer these questions, a large panel of mark- ers of inflammation and those related to inflammation should be tested together in prospective studies. However, before choosing the molecules to be tested, a first step should be to look for associations between hs-CRP and these markers of inflammation or related to inflammation in healthy individuals.