THE VITA PROJECT - PHENOTYPIC RESISTANCE TO ACTIVATED PROTEIN-C AND FV LEIDEN MUTATION IN THE GENERAL-POPULATION

Resistance to activated protein C (APC) has been recently identified a s a common abnormality of the clotting system that significantly incre ases the risk of venous thromboembolism. The distribution of plasma re sponse to APC in the general population and the variables potentially influencing it an however unknown. In this study, we analyzed the data from the first 4,000 subjects enrolled in the Vicenza Thrombophilia a nd Atherosclerosis (VITA) Project to identify the demographic and labo ratory variables affecting the plasma response to APC. Plasma response to APC, expressed as APC-ratio, was significantly influenced not only by the presence of the FV Leiden mutation but also by the aPTT ratio, triglycerides, fibrinogen and cholesterol level and by pill use, ABO blood group, gender, smoke, body-mass index and age. The effect of the se variables was independent of the presence of the FV Leiden mutation , and adjustment for their effect improved the discriminating efficien cy of the APC-ratio for the presence of the FV Leiden mutation. Notwit hstanding adjustment, the APC ratio was unsuitable for screening purpo ses in the general population (positive predictive value 82.7%).