Thus, patients with the same LDL-levels may be at different cardiovascular risk. Indeed, small dense LDL represent an emerging cardiovascular risk factor, independent of traditional risk factors including total LDL levels. Several studies implicated a direct role of sdLDL in atherogenesis and thus provided evidence that the role of sdLDL goes XAV939 Wnt/beta-catenin inhibitor beyond a MG132 simple marker of metabolic disturbances. These particles exhibit reduced binding capacities to LDL-receptors and show a stronger affinity to the extracellular matrix within the vascular wall making them more prone to oxidative modification. The mechanism leading to elevated levels of inflammatory monocyte subpopulations in patients with atherosclerotic vascular disease is poorly understood. Therefore, the aim of this study was to examine whether monocyte subsets are associated with sdLDL in patients with stable, coronary artery disease. In addition, we tested whether sdLDL serum levels correlate with pro- and anti-inflammatory cytokines. In the present study, we provide evidence for the first time that in patients with stable coronary artery disease and high levels of pro-atherogenic small dense LDL particles, monocyte subset distribution is skewed to a more “pro-inflammatory” profile with elevated levels of non-classical monocytes and reduced levels of classical monocytes. This association was independent of BMI, statin dose and hsCRP-levels. The small proportion of intermediate monocytes did not differ according to sdLDL tertiles. Monocytes and monocyte-derived macrophages have been implicated in all stages of atherogenesis, from initiation and progression, to destabilization and rupture of atherosclerotic lesions with possible detrimental outcome. Monocyte heterogeneity was established by Passlick et al by staining cells with the LPS co-receptor CD14 and the Fc��III receptor CD16. The vast majority of cells did not stain for CD16 and were termed ��classical monocytes��, while the CD16+ subclass was named ��non-classical monocytes��. The latter population was soon considered as pro-inflammatory, as these cells responded with a stronger production of inflammatory cytokines such as TNF-�� upon activation and were shown to be proportionally elevated in diseases with underlying inflammation such as sepsis, tuberculosis and HIV infection. In a study including both patients with stable CAD and acute coronary syndrome, monocyte subset distribution was skewed to an increased proportion of CD16-positive cells when compared with healthy controls. Hypercholesterolemia is considered a major risk factor for the development of atherosclerosis. As a response to the accumulation and modification of LDL within the vessel wall, monocytes migrate into the intima taking up modified LDL-particles thereby initiating plaque growth. Subset-specific interaction with lipoprotein metabolism has been suggested by several in vitro and in vivo studies, indicating specific expression of scavenger receptors and binding of oxidized and enzymatically modified lipoproteins. In a small cross-sectional study of hypercholesterolemic patients, HDL levels were inversely correlated with non-classical monocytes, while other subpopulations were not related to lipoprotein plasma levels. In another study of the same group evaluating a bigger group of hypercholesterolemic patients, the proportion of non-classical monocytes was associated with total cholesterol, triglycerides and LDL-cholesterol, the latter one showing only a non-significant weak correlation. Interestingly, in contrast to their first study, HDL-cholesterol did not correlate with NCM. In our study, including only patients with angiographically proven stable CAD, we could show a statistically significant inverse correlation between percentage levels of CM and both total cholesterol and LDL, while NCM did not correlate with either LDL, HDL or total cholesterol, which is in contrast to the above described findings in the literature.