The relation between apolipoprotein E (APOE) genotype and peripheral artery disease in patients at high risk for cardiovascular disease

Introduction: The apolipoprotein E gene (APOE) is associated with coronary heart disease and stroke, but the relation with peripheral artery disease (PAD) is unknown. We investigated the relation of APOE genotype with PAD and other types of vascular disease. Methods: The cross-sectional association between APOE genotype and ankle-brachial index (ABI) and vascular disease prevalence; and the prospective relation with incident PAD and other types of vascular disease (coronary artery disease, stroke and vascular mortality) were evaluated in 7418 patients from the Secondary Manifestations of ARTerial disease (SMART) study. This is a prospective cohort study in patients with cardiovascular disease or a cardiovascular risk factor. Analyses were adjusted for age and sex. Results: Mean age was 56.7 ± 12.4 years and 68% of the patients was male. APOE genotype frequencies were ε2ε2 1.3%; ε2ε3 9.9%; ε2ε4 2.4%; ε3ε3 56.9%; ε3ε4 26.7% and ε4ε4 2.8%. Median follow-up time was 8.1 years (IQR 5.4-11.4) in which 452 new PAD events occurred. The ε2ε2 genotype was significantly associated with a lower ABI (regression coefficient -0.04, 95%CI -0.07 to -0.01), increased PAD prevalence (prevalence ratio 1.54, 95%CI 1.01-2.17) and a higher risk of incident PAD (HR 2.31, 95%CI 1.29-4.12) compared with ε3ε3. No relations between APOE genotypes and other vascular disease were observed. Conclusion: Of the six APOE genotypes, the ε2ε2 variant is associated with an increased risk for PAD in patients at high risk for cardiovascular disease. No association was observed between APOE genotype and coronary artery disease, stroke or vascular mortality in this population.