Abstract 13330: Cardiorespiratory Fitness is Associated With Decreased Platelet Reactivity

Abstract

Introduction: Platelets are key mediators in atherosclerotic cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a major risk factor for atherosclerosis. However, little is known about the effects of CRF on platelet function. Methods: Platelet assays and cardiopulmonary exercise testing were conducted in the Framingham Heart Study (n= 3001). A linear mixed effects model was used to analyze associations between CRF (assessed by peak oxygen uptake [VO 2 ] in participants achieving a respiratory exchange ratio >= 1), and platelet reactivity traits from multiple platelet function assays: whole blood Multiplate impedance aggregometry (MP), Total-Thrombus Formation Analysis System (T-TAS), and light transmission aggregometry (LTA). Statistical models adjusted for relatedness, age, sex, and anti-platelet medications. Bonferroni correction for multiple statistical testing resulted in a significance threshold of p<7.35E-04. Results: Of 68 platelet traits analyzed, 31 traits passed the significance threshold, all with a direction of effect indicating higher CRF associated with decreased platelet reactivity. Significant traits spanned multiple platelet agonists. Our strongest associations were seen with MP after TRAP-6 (velocity, p=1.57E-26; AUC, p=2.33E-21; aggregation, p=5.30E-16) and ADP stimulation (velocity, p=1.63E-19; AUC, p=7.64E-17; aggregation, p=1.00E-11), and LTA after ristocetin stimulation (max aggregation, p=5.33E-11; AUC, p=1.11E-10). Conclusion: Our research adds to past work that shows CRF to be associated with reduced CVD by suggesting that decreased platelet reactivity may be involved mechanistically. We found significant associations with multiple platelet agonists, indicating higher CRF globally inhibits platelets; however, given the multiple strong associations after TRAP-6 and ADP stimulation, PAR-1 and purinergic signaling, respectively, may be most heavily involved. This is notable since each of these receptor pathways is directly or indirectly tied to anti-coagulant or anti-platelet therapies. Ultimately, our results suggest that CRF may be important for additional consideration in tailoring anti-platelet strategies.