BACKGROUND: The potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy. METHODS AND RESULTS: In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1. 2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors. CONCLUSIONS: The present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship.
RCT Entities:
BACKGROUND: The potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy. METHODS AND RESULTS: In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1. 2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors. CONCLUSIONS: The present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship.
Authors: Karen C Johnson; Aaron K Aragaki; Rebecca Jackson; Alex Reiner; Per Morten Sandset; Jan Rosing; Anders E A Dahm; Frits Rosendaal; JoAnn E Manson; Lisa W Martin; Simin Liu; Lewis H Kuller; Mary Cushman; Jacques E Rossouw Journal: Arterioscler Thromb Vasc Biol Date: 2015-12-17 Impact factor: 8.311
Authors: R Loeffen; T C Godschalk; R van Oerle; H M H Spronk; C M Hackeng; J M ten Berg; H ten Cate Journal: Heart Date: 2015-05-21 Impact factor: 5.994