Title
Tissue plasminogen activator and risk of myocardial infarction: The Rotterdam study
Author
van der Bom, J.G.
de Knijff, P.
Haverkate, F.
Bots, M.L.
Meijer, P.
de Jong, P.T.V.M.
Hofman, A.
Kluft, C.
Grobbee, D.E.
Gaubius Instituut TNO
Publication year
1997
Abstract
Background: Impaired fibrinolytic capacity, as assessed by euglobulin clot lysis time or plasma concentration of fibrinolytic parameters, has been associated with an increased risk of myocardial infarction (MI). We studied the association of a polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and activity) with the prevalence of MI. Methods and Results: A case-control study was performed. Subjects with a history of MI (n= 121) and controls (n=250) were drawn from the Rotterdam Study, a population based cohort study of 7983 subjects ≤ 55 years old. We determined TPA antigen and activity in plasma and genotyped all subjects for the Alu repeat insertion/deletion polymorphism in intron h in the TPA gene. Homozygosity for the insertion was associated with twice as many cases of MI as was homozygosity for the deletion (odds ratio. 2.24; 95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI; compared with that in the lowest quartile, the relative risks (odds ratio) in the second, third, and upper quartiles were 1.7 (CI.0.9-3.3), 2.3 (1.2-4.4), and 2.0 (1.03.8), respectively. When adjusted for body mass index, HDL and total cholesterol, systolic and diastolic blood pressures, and current smoking, the risk associated with TPA antigen concentration was attenuated. Increased concentrations of TPA activity tended to be associated with an increased risk of MI. Conclusions: This study provides evidence for an independent association of the insertion allele of the insertion/deletion polymorphism in the TPA gene with nonfatal MI. Increased TPA antigen is associated with an increased risk of MI; however, this association was not independent of cardiovascular disease risk factors.
Subject
Biology
Cardiovascular diseases
Fibrinolysis
Thrombolysis
Adult
Allele
Coronary risk
Diastolic blood pressure
Gene insertion
Genotype
Heart infarction
Major clinical study
Survival rate
Aged
Case-Control Studies
Cohort Studies
Cross-Sectional Studies
DNA Transposable Elements
Female
Gene Deletion
Humans
Immunologic Techniques
Male
Middle Aged
Myocardial Infarction
Polymorphism, Genetic
Prospective Studies
Risk Factors
Tissue Plasminogen Activator
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TNO identifier
233956
ISSN
0009-7322
Source
Circulation, 95 (12), 2623-2627
Document type
article