Frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 gene for aspirin resistance in elderly chinese patients with cardiovascular disease

Abstract

Background: Cardiovascular disease (CVD) is an important cause of mortality in elderly patients worldwide. Aspirin resistance has been well reported in CVD. Objective: The frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 (COX-1) gene for aspirin resistance have not been reported in elderly patients with CVD. We therefore undertook this study to evaluate these associations among elderly Chinese patients with CVD. Methods: Four hundred thirty-one elderly Chinese patients with CVD receiving daily aspirin therapy (≥75 mg) over 1 month were enrolled. Platelet aggregation was measured by light transmission aggregometry (LTA) and thromboelastography platelet mapping assay (TEG) using arachidonic acid (AA) as a stimulus. The median follow-up was 1.8 years. Results: After the median follow-up, aspirin-resistant patients were at an increased risk of the composite endpoint compared to nonresistant patients by LTA AA + TEG AA (23.7 vs. 9.2%, p = 0.025). Additionally, Cox proportional hazards regression modeling demonstrated that aspirin resistance and cerebrovascular disease were associated with major adverse long-term outcomes (HR for aspirin resistance = 2.31, 95% CI 1.11-4.81, p = 0.026). The variant G-allele of COX-1 rs1330344 (-1676 A/G) significantly increased the risk of aspirin resistance defined by LTA AA + TEG AA (OR = 1.82, 95% CI 1.13- 2.92, p = 0.01). Conclusions: Aspirin resistance, evaluated by LTA AA + TEG AA, is associated with an increased risk of adverse clinical events in elderly Chinese patients with CVD. The variant G-allele of COX-1 rs1330344 is significantly associated with aspirin resistance defined by LTA AA + TEG AA.