The development of atherothrombosis is strongly influenced by the complex interplay between platelet function, inflammation, and hypercoagulability. The progression of a stable plaque to a vulnerable state leading to occlusive thrombus generation in selected patients is a discontinuous and unpredictable process. Transition from an asymptomatic disease state to the sudden occurrence of myocardial infarction may be preceded by inflammation and the development of blood vulnerability characterized by measurements of heightened platelet function and hypercoagulability. The characterization of mechanisms responsible for the transition from an asymptomatic disease state to an unstable disease state and identification of “thrombogenic” phenotype is an important goal in the treatment and prevention of acute thrombotic complications. Therefore, linking vulnerable blood (“thrombogenic” phenotype) to the vulnerable patient who is at risk for thrombotic complications is important in the optimal diagnosis and treatment of patients with coronary artery disease (CAD) [1].

Systemic and local inflammation has been strongly implicated in the initiation, progression, and vulnerability of an atherosclerotic plaque. Various prospective studies have established that C-reactive protein (CRP) is an important systemic inflammation marker predictive of future myocardial infarction and stroke. Elevated CRP has been associated with CAD risk in a generally healthy population with an odds ratio of 1.45, and data from 25 prospective cohort studies in subjects with and without documented heart disease have demonstrated that high-sensitivity CRP (hs-CRP) concentrations are independently associated with the future risk of cardiovascular events [2, 3]. Experimental, clinical, and epidemiological evidences support the hypothesis that CRP is a “marker” as well as an active participant in the development of atherothrombotic complications [4, 5, 6]. In vitro studies suggest a direct influence of CRP on endothelial and platelet function. It has been reported that CRP stimulates procoagulant activity by stimulating tissue factor (TF) release or by reducing fibrinolysis [6]. In autopsy studies, CRP immune reactivity was demonstrated in atherosclerotic but not normal arteries, and also, the presence of high levels of CRP was demonstrated in fibrous tissue and atheroma of atherectomy specimens from patients with unstable angina and myocardial infarction compared to patients with stable angina [7]. CRP is an important regulator of endothelial cell activation and dysfunction. CRP can upregulate the surface expression of proinflammatory adhesion molecules such as intracellular cell adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in addition to TF on endothelial cells, vascular smooth muscle cells, and monocytes. Thus, CRP can induce the adhesion of platelets and monocytes to endothelial cells to promote atherothrombotic processes. In addition, CRP is known to induce MCP-1 and TF from monocytes. Finally, the inhibition of nitric oxide, prostaglandin I₂ (PGI₂), and plasminogen activator inhibitor type 1 (PAI-1) release may also contribute to the prothrombotic actions of CRP. These effects of CRP have been attributed to the binding of monomeric CRP that results from the conformational rearrangement of native CRP to FcγRIII (CD16) receptor and complement protein (C1q) [7]. A strong association between CRP and hypercoagulability (high thrombin-induced platelet–fibrin clot strength measured by thrombelastography) at different stages of CAD has been demonstrated supporting the significant role of CRP in plaque instability and subsequent thrombotic complications [1].

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