C-reactive protein and venous thromboembolism: causal or casual association?

The plasma concentration of C-reactive protein (CRP), the first acute-phase protein to be identified, increases dramatically following tissue injury or inflammation. Although the physiological role of CRP is still not fully known, it has been suggested that concentrations might increase as part of the acute-phase response for facilitating non-specific immune functions, defense against bacterial pathogens, clearance of apoptotic and necrotic cells to prevent immunization against autoantigens and acceleration of the repair process. In agreement with the evidence that inflammation plays a pivotal role in the pathogenesis of atherosclerosis, CRP concentrations have been associated with cardiovascular disease, and measurement of CRP has therefore been proposed as a valuable aid to predict and stratify the risk of myocardial infarction and stroke. Recently, some clinical and biological evidence in support of the hypothesis that CRP might be also involved in the onset of venous thrombosis have emerged. Native and monomeric CRP exert several prothrombotic activities, including activation of blood coagulation, impairment of the endogenous fibrinolytic capacity, and stimulation or enhancement of platelet adhesiveness and responsiveness. Epidemiological investigations have also shown that CRP concentrations are associated with increased risk of venous thromboembolism and, even more interestingly, that statins might be effective in reducing the risk of this pathology. Although there is increasing emphasis that CRP might not only be a marker but also an active player in the development of venous thrombosis, further evidence is needed to establish which event comes first--thrombosis or inflammation.