Abstract:
BACKGROUND AND PURPOSE:Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/5G polymorphism affects PAI-1 gene transcription with lower levels of plasma PAI-1 in the presence of the 5G allele. We investigated whether plasma PAI-1 and 4G/5G genotype would predict the occurrence of cardiovascular events at old age. METHODS:Relative risks for cardiovascular events and all-cause mortality were obtained in strata of PAI-1 activity and 4G/5G genotype in a population-based study of 637 Dutch elderly with 7.8 years of follow-up. RESULTS:The 4G/4G genotype was associated with a decreased risk of stroke (relative risk [RR]=0.4; 95% CI, 0.2 to 0.9), transient ischemic attack (RR=0.3; 95% CI, 0.1 to 0.8), and cardiovascular mortality (RR=0.5; 95% CI, 0.3 to 1.0) after adjustment for age, sex, and time of blood sampling. 4G carriers had an increased risk of myocardial infarction, but this was not statistically significant. Subjects with high plasma PAI-1 activity were at increased risk of stroke (RR=3.3 in highest versus lowest tertile; 95% CI, 1.5 to 7.1), cardiovascular mortality (RR=2.3; 95% CI, 1.2 to 4.4), and all-cause mortality (RR=1.5; 95% CI, 1.1 to 2.1). CONCLUSIONS:Our results provide support for a protective effect of the 4G allele against stroke, which is notable given the direct relationship between stroke and PAI-1 activity. We hypothesize that a local increase in tissue PAI-1 associated with the 4G allele may stabilize plaques, thereby reducing the risk of cerebrovascular disease.
journal_name
Strokejournal_title
Strokeauthors
Hoekstra T,Geleijnse JM,Kluft C,Giltay EJ,Kok FJ,Schouten EGdoi
10.1161/01.STR.0000098004.26252.EBsubject
Has Abstractpub_date
2003-12-01 00:00:00pages
2822-8issue
12eissn
0039-2499issn
1524-4628pii
01.STR.0000098004.26252.EBjournal_volume
34pub_type
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