Platelet Activity in Vascular Surgery and Cardiovascular Events (PACE)

The main aim is to determine whether preoperative platelet activity measurements are independently associated with short-term cardiovascular events in PAD patients undergoing open non-emergent lower extremity vascular surgery. We will characterize the platelet phenotype in 350 PAD patients before vascular surgery and use Cox proportional hazard models to determine the independent association of the platelet phenotype with risk of cardiovascular events in the first 30 days after surgery. The next aim is to determine whether platelet activity measurements are independently associated with long-term cardiovascular events in patients with established PAD. We will characterize the platelet phenotype following surgery and use Cox proportional hazards models to determine the independent association of the platelet phenotype with risk of long-term composite of myocardial infarction, stroke, or all-cause mortality with a mean follow-up of 2-years following vascular surgery. The final goal is to investigate mRNA-microRNA co-expression profiles in patients with and without elevated platelet activity measurements. We will establish the relationship between differentially expressed microRNAs and their target mRNAs related to platelet activity and identify new diagnostic markers and potential therapeutic targets of increased platelet activity.

Blood collection at three different time points (before surgery, following surgery while still in the hospital, and at the subjects' first return visit to the vascular surgeon following surgery) will allow us to assess the dynamic change in platelet activity, coagulation and inflammation during the perioperative period. We believe that markers of clotting and bleeding will change during the course of surgery, and that some of these markers may be used to help predict the likelihood of developing a clotting or bleeding event following surgery. The long-term goal is to develop a clinically useful assessment of platelet activity, thrombin generation, coagulation and inflammation for risk stratification that may ultimately serve as a target for therapeutic intervention.