High-Intensity Exercise Training Improves Basal Platelet Prostacyclin Sensitivity and Potentiates the Response to Dual Anti-Platelet Therapy in Postmenopausal Women

Abstract

The risk of thrombotic events dramatically increases with age and may be accelerated in women by the cessation of endogenous estrogen production at menopause. Patients at risk of thrombosis are prescribed dual anti-platelet therapy (DAPT; aspirin and a P2Y12 antagonist) and are encouraged to participate in regular physical activity, as these modalities improve nitric oxide and prostacyclin-mediated inhibition of platelet aggregation. Methods: We assessed prostacyclin sensitivity as well as basal platelet reactivity with and without in vitro DAPT before and after an 8-week high-intensity exercise training program in 13 healthy, sedentary postmenopausal women. The training intervention consisted of three 1 h sessions per week. Isolated platelets were analyzed for thromboxane A2 receptor, thromboxane A2 synthase, cyclooxygenase-1, and prostacyclin receptor protein expression. Additionally, plasma 6-keto prostaglandin F1α and thromboxane B2 levels were determined. Results: Exercise training made platelets more sensitive to the inhibitory effects of prostacyclin on thromboxane-, collagen-, and adenosine 5′-diphosphate (ADP)-induced aggregation, as well as thrombin-receptor activator peptide 6- and ADP-induced aggregation with DAPT. However, there was no change in protein expression from isolated platelets or plasma thromboxane B2 and prostacyclin levels following training. Conclusion: Together, these findings emphasize the importance of promoting physical activity as a tool for reducing thrombotic risk in postmenopausal women and suggest that training status should be considered when prescribing DAPT in this cohort.

Keywords

• dual anti-platelet therapy
• exercise
• menopause
• platelets
• coagulation
• thrombosis