Seminars in vascular medicine
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Progressive atherosclerosis followed by plaque rupture is the leading cause of acute cardiovascular events. Inhibition of platelet aggregation by acetylsalicylic acid (aspirin) reduces recurrent cardiovascular events in secondary prevention trials. By extracting data from available randomized trials that examined aspirin prevention in persons without previously known cardiovascular disease, we evaluated the use of aspirin as a primary prevention measure. ⋯ In healthy men above 45 years of age, men with an increased cardiovascular risk profile, and persons with diabetes mellitus or hypertension, the use of aspirin reduces the incidence of myocardial infarction and has a neutral effect on cerebrovascular events. The protective effect of aspirin is apparently most prominent in those persons with an increased risk of manifest atherosclerotic vascular disease. Notwithstanding these results, for each patient it remains essential to balance the cardiovascular risk profile against the small increased risk of bleeding complications when prescribing aspirin.
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This article focuses on the role of the tissue factor (TF)-thrombin pathway in cardiac ischemia-reperfusion (I/R) injury. We and others have used rabbit models of cardiac I/R injury to show that anti-TF therapy prevents the transient decrease in regional myocardial blood flow, reduces platelet and fibrin(ogen) accumulation, and reduces infarct size. At present, the mechanism by which TF-initiated coagulation contributes to myocardial injury is not established. ⋯ In contrast, inhibition of thrombin reduced infarct size to a similar extent as anti-TF therapy. We propose that the TF-thrombin pathway may contribute to myocardial injury by an additional mechanism that is not dependent on fibrin deposition but involves activation of protease activated receptor 1 (PAR-1) on vascular endothelial cells and cardiac myocytes. Anti-TF therapy would inhibit both thrombin-dependent fibrin deposition and thrombin-dependent PAR-1 signaling.