ID: 73: ATHEROTHROMBOSIS, THROMBOPHILIA, AND RELENTLESS PROGRESSION OF CORONARY ARTERY DISEASE

Introduction Atherothrombosis involves a complex pathway often initiated by ulceration of an atherosclerotic plaque with platelet aggregation and thrombus formation. In the concurrent presence of familial and acquired thrombophilia, coronary artery disease (CAD) is often accelerated despite conventional lipid lowering, anti-platelet, and vascular interventions (stents, angioplasty, bypass). In a cohort of 30 patients with premature CAD and atherothrombosis, often worsening despite maximal conventional medical-surgical intervention, our specific aim was to describe major concurrent thrombophilia as a treatable component of atherothrombosis. Methods In 30 patients with premature, severe, and progressive CAD and atherothrombosis, despite maximal lipid lowering, anti-platelet therapy, and direct intervention (stents, angioplasty, coronary artery bypass grafts), we assessed for the presence of familial and acquired thrombophilia, with comparison to 110 healthy normal controls without CAD, and to 110 patients without CVD but with previous venous thromboembolism (VTE). Results The 30 patients (21 men, 9 women) had severe CAD despite anti-platelet treatment, maximal lipid lowering therapy (mean±SD LDLC was 82±46, median 72 mg/dl), and direct arterial intervention. The patients9 first cardiac event occurred at age 46±12, median 47 years, and current age was 59±12, median 59 years. Most patients had suffered from multiple myocardial infarctions (12 had multiple stents, 8 were post cardiac bypass), 8 had previous VTEs, 3 had TIAs and one had preeclampsia. Compared with 110 healthy normal controls, the 30 patients with CAD-atherothrombosis were more likely to have high homocysteine (20% vs 5%, P=0.014), Factor Leiden Heterozygosity (23% vs 2, P=0.006), lupus anticoagulant (27% vs 2%, P=0.003), high anticardiolipin antibody IgM (17% vs 3%, P=0.005), high factor VIII (30% VS 7%, P=0.007), high Factor XI (25% vs 3%, P=0.003), low antigenic protein C (26% vs 6%, P=0.18) and low antigenic protein S (21% vs 2%, P=0.007). Of the 8 patients who had CABG, 2 had multiple early venous graft failure (25%) compared to the historical one year graft failure of 10–15%. Thrombophilia did not differ across the atherothrombosis/CAD and VTE groups, except that the lupus anticoagulant was more common in the CAD-atherothrombosis patients than in the VTE patients (27% VS 4%, P=0.002). Conclusion In the presence of premature-aggressive CAD, despite maximal lipid lowering, anti-platelet therapy, and angioplasty-stent-bypass interventions, it is clinically valuable to assess for anticoagulant-treatable thrombophilia, which interacts with the atherosclerosis with resultant atherothrombosis. The patterns of thrombophilia in atherothrombotic patients do not differ from those in VTE without CAD, except for the lupus anticoagulant.