In humans, many studies have suggested that PAI-1 gene polymorphisms, possibly leading to higher PAI-1 levels, are an independent risk factor for major adverse cardiovascular events (MACE) including myocardial infarction (MI) (164–167) and ischemic stroke (168), as well as coronary heart disease (CHD) (169), venous thrombosis (170–172), and atherosclerosis (173). This evidence concerns the gene SERPINE1 and atherosclerosis.