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.
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.
Authors: Gonzalo Sirgo; José Luis Pérez-Vela; Pablo Morales; Manuel Del Rey; Joan Vendrell; Cristina Gutierrez; Jordi Rello Journal: Intensive Care Med Date: 2006-03-01 Impact factor: 17.440
Authors: Adriano de Paula Sabino; Daniel Dias Ribeiro; Caroline Pereira Domingueti; Mariana Silva Dos Santos; Telma Gadelha; Luci Maria Santana Dusse; Maria das Graças Carvalho; Ana Paula Fernandes Journal: Mol Biol Rep Date: 2011-03-04 Impact factor: 2.316
Authors: C Nafría; I Fernández-Cadenas; M Mendioroz; S Domingues-Montanari; M Hernández-Guillamón; J Fernández-Morales; A Del Río-Espínola; D Giralt; L Deu; P Delgado; A Rosell; J Montaner Journal: Stroke Res Treat Date: 2011-06-09