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Thrombin, Inflammation, and Cardiovascular Disease: CVD risk

To support this position, studies of the plasma levels of prothrombin (a key procoagulant protein, but not an inflammation-sensitive protein) and/or the prothrombin G20210A genotype associated with plasma levels, generally have been null for CVD risk in most cases while consistently positive for venous thrombosis. Also, several studies have examined the anticoagulant proteins and their relationship to CVD. As an ancillary study to the Thrombolysis in Myocardial Infarction Phase II trial of thrombolytic therapy, we demonstrated that in those entering the health system with MIs, anticoagulant proteins, such as protein C and antithrombin, were elevated, not decreased. We have also demonstrated that in otherwise healthy adults tissue factor pathway inhibitor levels were higher, not lower, in those with increased measures of subclinical disease based on ankle-brachial BP index and carotid ultrasonography. www.cfp-for-you.com
Also, Folsom and colleagues showed in the Atherosclerosis Risk in Communities study that protein C was weakly, but positively, associated with CVD, even though protein C is not a strong acute phase reactant. This is counter to expectations based on the hypercoagulable hypothesis (ie, lower levels, not higher levels, of anticoagulants would be found in those either with, or at risk for, CVD), but rather supports the inflammatory hypothesis: inflammation, rather than the process of clotting, is more related to CVD risk.
Having suggested that the principal mechanism for association of some coagulation factors with CVD is through their nature as inflammation-related factors, it remains possible that these factors may also reflect risk because, once they are elevated, higher levels increase the likelihood of blood clot formation. Using fibrinogen as an example, possible mechanisms by which higher levels of fibrinogen might be related to increased likelihood of blood clotting include increased platelet crosslinking, increased fibrin clot formation, and increased blood viscosity, among others.