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Objective-Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results-Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (PϽ0.05). Fibrin of young CAD patients was stiffer (Pϭ0.002), made of numerous (Pϭ0.002) and shorter fibers (Pϭ0.04), and lysed at a slower rate than that of controls (Pϭ0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions-This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. Key Words: acute coronary syndromes Ⅲ coagulation Ⅲ fibrinolysis Ⅲ pathophysiology Ⅲ fibrinogen Ⅲ thrombophilia T he mechanical properties of clots and their major constituent fibrin are normally finely tuned to optimize bleeding control while also minimizing their effect on atherothrombosis. 1,2 A decreased rate of fibrinolysis and increased thrombosis are generally associated with stiff clots, although such relationships are complex. 3,4 Many factors that affect clot structure have a great impact on the mechanical properties fibrin and fibrinolysis through modifications of various steps in the fibrin polymerization process and clot stabilization. 1,4,5 See page 2419Premature coronary artery disease (CAD) is associated with increased plasma levels of prothrombotic and proinflammatory biomarkers, including fibrinogen and plasminogen activator inhibitor (PAI) type 1, which are known to favor hypofibrinolysis 6 and to be independent predictors of CAD. 7,8 Epidemiological studies have also revealed a relationship between myocardial infarction (MI) and reduced permeability and increased stiffness of fibrin, especially in young post-MI patients. 9 These aspects of altered fibrin clot network architecture were not found to be attributable to classic risk factors including fibrinogen concentrations or common polymorphisms. 2 However, the relationships among premature CAD, abnormal fibrin physical properties, and hypofibrinolysis remain little explored. The lack of appropriately designed studies of the physical properties of fibrin, including simultaneous determination of viscoelastic and morphological properties o...

HE OPTIMAL INTERVENTION IN the treatment strategy of patients presenting with acute coronary syndromes without ST-segment elevation (NSTE-ACS) has been debated for years. Numerous studies, randomized trials, and metaanalyses have investigated the potential benefits of invasive over conservative strategies, and most have suggested a prolonged advantage of an invasive approach for the prevention of death or myocardial infarction (MI), particularly among high-risk patients. 1-14 If an invasive strategy is generally accepted to be the best option and is currently recommended in high-risk patients, little information is available regarding the optimal timing of coronary angiography and intervention. 15,16 Only 2 randomized studies evaluated the timing of intervention (early vs late) with patients in the 2 study groups receiv-Author Affiliations are listed at the end of this article.

Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

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