G20210A protrombin gene variant and clinical outcome in patients with a first acute coronary syndrome

Background and objectives: The prognostic value of the G20210A prothrombin gene polymorphism in patients with a first acute coronary syndrome has not been previously assessed. We conducted a prospective study to investigate this issue. Design and methods: Genotyping at the 20210 prothrombin gene locus was performed in 162 patients with a first episode of myocardial infarction (MI) or unstable angina (UA) occurring before 65 years of age. Patients were stratified according to cardiovascular risk factors and to treatment strategy. The subsequent two-year relative risk (RR) of adverse events (death, MI and UA) was adjusted for possible confounders and analyzed according to genotype, risk factor category, and treatment allocation. Results: In the entire study population, the prothrombin variant did not significantly increase the two-year risk of events: the adjusted RR for GA vs GG carriers was 1.82 (95% CI 0.68-4.89). However, in the absence of traditional cardiovascular risk factors the risk of events was consistently higher: among the 46 patients without hypertension, diabetes and hypercholesterolemia, GA vs GG carriership was associated with an adjusted RR at two years of 5.64 (95% CI 1.07-29.84). The gene variant also enhanced the risk of events among the 98 patients who did not undergo myocardial revascularization procedures (RR for GA vs GG: 2.89, 95% CI 1.04-8.00), but not among those who did. Interpretation and conclusions: The present prospective study suggests that heterozygosity for the G20210A prothrombin polymorphism adversely affects prognosis after a first acute coronary syndrome in the subgroup of patients without metabolic risk factors and in those not treated by revascularization procedures.