Abstract 3477: Platelet Hyper-responsiveness in Aspirin-Treated Patients with Clinical Cardiovascular Disease Compared to Matched High Risk Controls
Background: Platelet hyper-responsiveness to activating stimuli during aspirin (ASA) therapy may discriminate between high risk subjects who have developed acute thrombotic cardiovascular disease (CVD) events (coronary disease and stroke) and those who are at increased risk but are disease free. We hypothesized that subjects with documented CVD would have greater platelet reactivity on ASA therapy compared to matched high risk non-CVD subjects.
Methods: Subjects (N=228; 61 +/− 8 yrs, 69% male, 60% white) were selected from families with known CVD; 114 had prevalent CVD and were matched on age, sex, and race to 114 apparently healthy controls with risk factors but without clinical CVD. CVD risk factors were measured and therapy adherence was determined by questionnaires. Platelet reactivity on 81 mg ASA/day was determined by whole blood (WB) aggregometry, platelet function analyzer (PFA) closure time, thromboxane B2 (TxB2) release ex vivo, and urinary excretion of 11-dehyrothromboxane B2 (Tx-M) in vivo. Results. CVD cases had greater platelet reactivity by all measures, both unadjusted, and adjusted for age, sex, race and adherence (Table⇓). Multivariable adjustment for cardiac risk factors and statin therapy eliminated case-control differences for Tx-M, but not for the ex vivo measures of platelet activation. ASA therapy duration in CVD subjects (8.8 +/− 6.2 yrs) was not related to platelet function.
Conclusions: Greater residual platelet reactivity exists during ASA therapy in CVD subjects compared to matched high risk controls, even controlling for CVD risk factors and adherence to therapy. The data suggest that platelet hyper-responsiveness during ASA chemoprophylaxis may differentiate patients with CVD from those who are at risk for CVD, but have not developed it. Platelet hyper-responsiveness may be an intrinsic property of CVD, related to as yet unidentified environmental or genetic factors.