PB0802 - Eight-year body mass index trajectories are associated with altered platelet reactivity traits in Framingham Heart Study participants

Background: Rapidly changing 8-year weight trajectories are associated with an elevated risk for cardiometabolic disease independent of current BMI. Weight loss including via gastric bypass surgery , is associated with decreased thromboxane-dependent platelet activation.

Aims: To assess the associations between longitudinal BMI trajectories and platelet reactivity traits.

Methods: We included 3,378 Framingham Heart Study participants from the Third Generation Cohort, OMNI, and New Offspring Spouse cohorts (exams two and three). Participants were categorized into BMI trajectories based on mean BMI change over approximately eight years: (I) decreasing BMI <-0.5 ; (II) stable BMI >-0.5 to < 0.5 (reference trajectory); (III) increasing BMI ≥ 0.5 to 2.0; (IV) rapidly increasing BMI ≥ 2.0. Platelet traits were measured during the third examination cycle (2016-2019) using light transmission aggregometry and Multiplate impedance aggregometry.

Results: A decreasing BMI trajectory was associated with platelet hyperaggregation to 0.95µM ADP (known to activate P2Y1 receptors) (β = 0.133, SE=0.051, P=0.009). A rapidly increasing BMI trajectory was associated with hyperaggregation to 0.95µM ADP (β = 0.105, SE=0.052, P=0.045). Platelet hyperaggregation to 1.82µM of ADP ( known to activate P2Y12 receptors) was increased in participants on a decreasing BMI trajectory (β = 0.11, SE=0.048, P=0.031) and in participants with increasing trajectory (β = 0.103, SE=0.048, P=0.037). Collagen-induced platelet aggregation was lower in a decreasing BMI trajectory (β = -0.097, SE=0.05, P=0.048). A rapidly increasing BMI trajectory was associated with increased platelet aggregation in response to thrombin receptor activator for peptide 6 (β = 0.137, SE=0.05, P=0.01) and ADP (β = 0.104, SE=0.05, P=0.043). A rapidly increasing BMI was associated with higher platelet disaggregation (β = 0.074, SE=0.03, P=0.008) following ADP (5.71 µM) induced aggregation.

Conclusion(s): An increasing BMI trajectory may be associated with increased P2Y1, P2Y12, and protease-activated receptor-1 mediated platelet aggregation. Conversely, a decreasing BMI trajectory may be associated with P2Y1-mediated platelet hyperaggregability.