Inflammatory Markers in Coronary Artery Disease: Pathophysiological Mechanisms, Prognostic and Therapeutic Implications

Ignatios      Ikonomidis; Kimon      Stamatelopoulos; John      Lekakis; Dimitrios      Th. Kremastinos

Abstract

Several inflammatory proteins intervene with endothelium and haemostatic factors leading to plaque formation and rupture. Of these, C-reactive protein (CRP), monocyte/macrophage colony-stimulating factor (MCSF) and interleukin- 6 (IL-6) promote atherogenesis by inducing monocyte-macrophage activation, foam cell formation, platelet activation, tissue factor expression, release of other procoagulant cytokines or downregulation of atheroprotective cytokines, namely interleukin 10 and transforming growth factor b-1 (TGF-b1). CRP, MSCF and IL-6 are interrelated and have been found increased in circulation in both chronic CAD and acute coronary syndromes. IL-6 is also related to the extent and duration of LV dysfunction following reversible myocardial ischaemia. TGF-b1 has been found decreased in patients with CAD and inversely related with MCSF. More importantly, increased levels of CRP or MCSF and low levels of TGFb-1 predict adverse cardiovascular events in CAD patients independently of traditional risk factors. Moreover, in patients with chronic CAD, the predictive value of MCSF is additive and beyond that of CRP suggesting the need of a multimarker approach in assessing cardiovascular risk. Although several therapeutic strategies like vaccination against antigens promoting atherogenesis, cyclooxygenase inhibitors (aspirin, coxibs), statins, and ACE inhibitors may reduce the levels of these inflammatory markers, the impact on cardiovascular risk resulting from these changes is unknown. Thus, inflammatory markers may serve as independent prognostic markers as well as therapeutic targets.

Keywords: Inflammation, prognosis, C-reactive protein, macrophage-colony stimulating factor, aspirin