PACE: Platelet Activity in Vascular Surgery and Cardiovascular Events
Study Details
Study Description
Brief Summary
Pathological and clinical studies have consistently demonstrated that abnormalities in thrombosis and hemostasis play a major role in the pathogenesis of atherosclerosis and atherothrombosis. Screening for abnormalities in thrombosis and hemostasis by measuring platelet activity, thrombin generation, and markers of coagulation have been proposed to identify individuals at high-risk for cardiovascular events, however, it remains a research tool not ready for implementation in standard care.
The proposed study will add to the growing understanding of platelet activity and markers of coagulation in cardiovascular disease; examine a comprehensive battery of platelet activity markers, thrombin generation, markers of coagulation, and inflammatory biomarkers in subjects undergoing vascular surgery; and will provide important data on the mechanism of increased platelet activity using micro RNA, RNA and DNA expression profiling. The study design is prospective and the main outcome measures are platelet activity, coagulation markers and incident cardiovascular and bleeding events.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| PAD and CLI patients Subjects undergoing non emergent lower extremity revascularization |
Outcome Measures
Primary Outcome Measures
- Platelet activity measurements associated with short-term cardiovascular events in PAD patients [30-days]
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 intervention. 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.
Secondary Outcome Measures
- Association between platelet activity measurements and long-term cardiovascular events in patients with established PAD [Average follow-up of 5-years]
To determine whether platelet activity measurements are independently associated with long-term cardiovascular events in patients with established PAD. We will characterize the postoperative 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.
Other Outcome Measures
- mRNA-microRNA co-expression profiles in patients with and without elevated platelet activity measurements [30-days]
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 thus identify new diagnostic markers and potential therapeutic targets of increased platelet activity.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects undergoing non emergent lower extremity revascularization
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Use of aspirin within 48 hours prior to surgery
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Age > 21 years of age
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Able and willing to provide written informed consent for the study
Exclusion Criteria:
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Use of any therapeutic anticoagulant
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Use of any nonsteroidal antiinflammatory drug (ibuprofen, naproxen, etc.) within 72 hours
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Thrombocytopenia (platelet count<100) or Thrombocytosis (platelet count>500)
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Anemia (hemoglobin<9)
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Any known hemorrhagic diathesis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | NYU Langone Medical Center and School of Medicine | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
- National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Jeffrey Berger, MD, New York University Director of Cardiovascular Thrombosis
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14-00531
- R01HL114978