Abstract 2638: The Factor VII Activating Protease (FSAP) Polymorphism (G534E) Is Associated With An Increased Risk For Stroke And Mortality
FSAP is a plasma serine-protease that is localized within atherosclerotic lesions. The FSAP-Marburg I polymorphism (G534E) has been shown to be associated with late complications of carotid stenosis in humans and with a reduced capability to suppress vascular smooth muscle cell proliferation and neointima formation in an animal model. Therefore, we investigated the influence of this polymorphism on stroke, coronary events and mortality in a large population of elderly patients at risk for vascular disease (the PROSPER-study, n=5804) and on clinical restenosis (Target Vessel Revascularization) after a percutaneous coronary intervention (the GENDER-study, n=3104). The Marburg I polymorphism was associated with an increased risk of stroke (HR: 1.60, 95%CI: 1.13–2.28) and all-cause mortality (HR: 1.33, 95%CI: 1.04 –1.71). Surprisingly, carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95%CI: 0.34 –1.01). Plasma analysis showed that Marburg I homozygotes did not have any FSAP activity, whereas heterozygous patients had 50% of the normal FSAP activity. The Marburg I variant did not have any effect on the risk of coronary events. The observed increase in stroke risk in Marburg I carriers could be a consequence of hyper-proliferation of smooth muscle cells. The possible protective effect on restenosis could be the result of a reduced activation of zymogens such as factor VII and pro-urokinase which are involved in haemostasis and matrix remodeling.