title: Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men.
abstract: Hypofibrinolysis as measured with overall clot lysis assays is associated with risk of arterial thrombosis. Individual components of the fibrinolytic system, however, have not been studied extensively in relation to arterial disease, or results of studies were inconsistent. The relation between plasminogen and alpha2-antiplasmin levels and cardiovascular risk factors and the association between plasminogen, alpha2-antiplasmin, tissue-plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) and risk of myocardial infarction was investigated in the Study of Myocardial Infarctions Leiden (555 men with a first myocardial infarction and 635 controls). alpha2-antiplasmin was associated with age and lipid levels, whereas plasminogen correlated with lipids, C-reactive protein, and smoking. Increased levels of all fibrinolytic factors were associated with myocardial infarction. Age-adjusted odds ratios (ORs; 95% confidence interval) for quartile 4 compared with 1 were 1.7 (1.2-2.3) for plasminogen, 1.9 (1.3-2.6) for alpha2-antiplasmin, 1.7 (1.2-2.3) for t-PA, and 1.7 (1.2-2.4) for PAI-1. After adjusting for cardiovascular risk factors, only alpha2-antiplasmin levels remained associated with risk (OR, 1.4; [1.0-2.0]). t-PA and PAI-1 levels predominantly reflected lipid levels, whereas plasminogen reflected the inflammatory state. Concluding, elevated alpha2-antiplasmin levels are independently associated with risk of myocardial infarction. t-PA, PAI-1, and plasminogen levels appear to reflect other cardiovascular risk factors.
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mirjam E
authors.initials: ME
authors.lastname: Meltzer
authors.forename: Carine J M
authors.initials: CJ
authors.lastname: Doggen
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
mesh_terms: D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000502:physiology*; D016022:Case-Control Studies; D005342:Fibrinolysis / Q000502:physiology; D005343:Fibrinolytic Agents / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology*; D010958:Plasminogen / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000097:blood; D012307:Risk Factors; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis
chemical_list: D001798:Blood Proteins; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator