Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease.
The 4G/5G polymorphism of the PAI-I gene influenced not only plasma PAI-I antigen levels but also the time course of the progression to ACS in patients with coronary atherosclerosis.
Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1 (PAI-1) activity in plasma is a common finding in patients with coronary heart disease or venous thromboembolism, although its clinical significance is debated.
Our data suggest that PAI-1 promoter polymorphism influences the development of myocardial infarction through its effect on thrombus formation in patients with preexisting coronary atheroma.
Results from these studies further suggest that individuals with this responsive 2/2 PAI-1 genotype may reflect the additional inherent potential for later HTG-VLDL- or Lp(a)-induced fibrinolytic dysfunction, resulting in the early initiation of thrombosis, atherogenesis, and coronary artery disease.
Familial high PAI levels with concurrent hypofibrinolysis co-segregated with familial combined hyperlipidemia, both being independent risk factors for premature coronary heart disease.
In a sample of both 83 healthy individuals and 105 young patients with coronary artery disease from Sweden, the frequency of the 4G allele is roughly 0.5, and those individuals homozygous for the 4G allele have higher levels of PAI-1 than those with other genotypes (29% higher).