| Fibrinolysis, inflammation and cardiovascular disease : epidemiological studies on plasminogen activator inhibitor-type 1 and C-reactive protein | Paperbackby Tiny Hoekstra (Author)
| 1 Used starting at: | $59.50 |
| |
| | Binding: | Paperback | | Publication Date: | 2003 |
|
EDITORIAL REVIEWS |
Product Description
Plasminogen activator inhibitor-type 1 (PAI-1) is the main inhibitor of fibrinolysis and a potential risk factor for cardiovascular disease. In addition to its regulating role in fibrinolysis, PAI-1 may have detrimental effects in the cardiovascular system also through other processes, e.g. inflammation. Although PAI-1 is generally elevated in the presence of cardiovascular disease, it is not yet clear whether it is a causal risk factor. A polymorphism in the promoter region of the PAI-1 gene, the 4G/5G-polymorphism, affects the transcription of the PAI-1 gene, yielding higher blood levels of PAI-1 for the 4G-allele. In case of a causal role of PAI-1 in cardiovascular disease, an increased cardiovascular risk would be expected for the 4G-allele.
The general objective of the studies in this thesis was to examine whether PAI-1 and the 4G/5G-polymorphism are associated with cardiovascular risk. Both associations with markers of atherosclerosis and clinical end points were studied. Because of the acute-phase properties of PAI-1, we additionally examined the role of C-reactive protein (CRP), a sensitive marker of inflammation.
In the Arnhem Elderly Study, comprising 641 subjects aged 65-84 years, we observed a strong daytime fluctuation in PAI-1 activity with peak levels in the early morning. The diurnal pattern was clearly present for the 4G/4G and 4G/5G-genotypes, but not for the 5G/5G-genotype. These findings raised the hypothesis that 5G-homozygotic persons may be relatively protected from the early morning peak incidence in cardiovascular events.
In a population of 208 smoking men the 4G/5G-polymorphism was not associated with two non-invasive markers of atherosclerosis, i.e. common carotid intima-media thickness and the ankle-brachial index. Neither did we observe consistent associations between the 4G/5G-polymorphism and coronary stenosis after pooling three similar case-control studies (n = 776) with angiographically determined coronary atherosclerosis. |
|
