Abstract
BackgroundThe clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.MethodsWe studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.ResultsThe frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).ConclusionsOur study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.
Highlights
The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging
In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) we found that the presence of PlA2 allele associated with a significantly worse prognosis with a higher incidence of cardiac death, acute myocardial infarction (AMI), and new myocardial revascularization
Since platelets play a major role in the development of atherosclerotic thrombosis and acute ischemic events, we investigated the role of the PlA2 gene polymorphism in higher risk populations such as patients with severe CAD requiring mechanical revascularization and hypertensive patients with previous cerebrovascular events
Summary
The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. Weiss et al [8] observed a strong association between the PlA2 polymorphism of the GP IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years, suggesting this polymorphism as an inherited risk factor for coronary thrombosis These findings were further expanded on peripheral artery disease by Mikkelson [9] who reported an association between PlA2 variant and the progression of atherosclerosis in the abdominal aorta. It is pivotal to accurately select the clinical phenotype that can be affected by the genetic variability To address this issue, and gain more inside on the role of PlA2 polymorphism on atherothrombotic disease, we performed a prospective study in a cohort of patients selected for angiography documented severe coronary artery disease (CAD), which needed percutaneous coronary intervention (PCI). A group of 100 healthy subjects was included as control population of our study
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