1. Robert W. Harrison, MD; Richard C. Becker, MD; Thomas L. Ortel, MD, PhD; Maragatha Kuchibhatla, PhD; Stephen H. Boyle, PhD; Zainab Samad, MD; Eric J. Velazquez, MD; Jennifer Wilson, BA; Cynthia Kuhn, PhD; Redford B. Williams, MD; Christopher M. O’Connor, MD; Wei Jiang, MD Duke University, Durham, NC Conclusions Robert W. Harrison, MD Duke Clinical Research Institute Durham, NC 27705 Robert.w.harrison@duke.edu Association Between Platelet Aggregation and Mental Stress Induced Myocardial Ischemia: Results From the REMIT Trial Background Objectives Methods Results Variable Normal LV response N=49 MSIMI N=105 P-value Demographics Age, mean (SD), years61.2 (9.4)63.1 (10.9)0.54 Gender (Female)2 (4.1)19 (18.1)0.02 Race (Non-White)5 (10.2)22 (21.0)0.10 Medical History Diabetes16 (32.7)28 (26.7)0.44 Current Angina10 (20.4)22 (21.0)0.95 Prior Myocardial Infarction15 (30.6)53 (50.5)0.07 Prior PCI28 (57.1)65 (61.9)0.57 Prior CABG22 (44.9)52 (49.5)0.59 Congestive Heart Failure1 (2.0)7 (6.67)0.23 Hypertension38 (77.6)79 (75.2)0.75 Hyperlipidemia47 (95.9)97 (92.4)0.41 Current Tobacco Use4 (8.2)19 (18.1)0.27 Depression5 (10.2)19 (18.1)0.21 Baseline Ejection Fraction, mean (SD), % 55.5 (8.7)53.3 (11.0)0.21 Medications Aspirin47 (95.9)102 (98.1)0.44 Additional Antiplatelet20 (40.8)49 (47.1)0.47 ACE-I35 (71.4)69 (66.4)0.53 ARB3 (6.1)16 (15.4)0.11 Calcium Channel Blocker9 (18.8)18 (17.3)0.83 Beta blocker38 (77.6)93 (89.4)0.051 Statin46 (93.9)99 (95.2)0.73 Table 1: Baseline characteristics Agonist Normal LV response N=49 Mean (SD) MSIMI N=105 Mean (SD) P-value Area Under the Curve (% x minutes) ADP 5 µM239.1 (127.5)237.5 (110.0)0.94 Epinephrine, 10 µM147.1 (146.0)139.5 (81.8)0.73 Collagen, 10 µM273.1 (102.1)278.6 (95.6)0.75 Serotonin, 5 µM+ ADP, 1 µM211.7 (119.0)206.0 (105.0)0.77 Serotonin, 5 µM+ Epinephrine, 2 µM243.9 (97.3)242.3 (89.7)0.92 Serotonin, 5 µM + Collagen, 2 µM232.1 (107.4)235.9 (91.3)0.83 Maximal Amplitude (%) ADP 5 µM53.6 (22.4)52.5 (20.7)0.77 Epinephrine, 10 µM28.5 (18.0)29.6 (15.8)0.71 Collagen, 10 µM67.0 (23.1)66.7 (19.6)0.93 Serotonin, 5 µM+ ADP, 1 µM50.0 (20.7)47.9 (18.7)0.53 Serotonin, 5 µM+ Epinephrine, 2 µM53.6 (18.3)52.5 (18.1)0.73 Serotonin, 5 µM + Collagen, 2 µM52.0 (23.4)52.9 (19.9)0.83 Table 2: Baseline resting platelet aggregation Figure: Adjusted change in platelet aggregation following mental stress Data are presented as least squares mean and standard error of the mean after adjustment for gender, baseline EF, and baseline platelet aggregation. *= P < 0.05 MSIMI vs. NLVR * * * * * * * Patients with coronary heart disease are susceptible to mental stress-induced myocardial ischemia (MSIMI), and patients susceptible to MSIMI have a poorer prognosis 1 MSIMI was more common than exercise induced myocardial ischemia in the REMIT trial, affecting 43% of patients with coronary heart disease 2 Patients with MSIMI have a poorer prognosis than those who do not exhibit MSIMI 1 Platelet activation is an important factor in acute coronary syndromes, and patients with depression and hostility have increased platelet reactivity. However, an association between platelet reactivity and MSIMI has not been established 1 Assess platelet aggregation before and after mental stress testing in patients with known coronary heart disease Hypothesis: Patients who are susceptible to MSIMI will have increased mental stress induced platelet aggregation compared to those without MSIMI REMIT NHLBI sponsored randomized clinical trial designed to assess the efficacy of escitalopram on MSIMI in patients with established coronary artery disease Eligible patients: Adults with clinically stable coronary heart disease (prior stenosis > 70%, or history of myocardial infarction or revascularization) Study Procedure Subjects were administered a series of 3 mental tasks: 1) mental arithmetic, 2) public speaking with anger recall, and 3) mirror tracing Blood samples were collected before and after mental stress testing to assess platelet aggregation Platelet Aggregation Aggregation determined with a BIO-DATA 4- channel platelet aggregometer. Variables of interest included the area under the platelet aggregation curve (AUC) and the maximal amplitude of platelet aggregation (%) Aggregation triggered by epinephrine (1, 2, 5, an 10 µM), collagen (1, 2, 5, and 10 µM), adenosine diphosphate (ADP; 1, 2, µM), and each agonist with serotonin (5HT; 10 µM) Endpoints: MSIMI: a decrease in EF of ≥ 8% or a new focal wall motion abnormality induced by mental stress testing Normal left ventricular response (NLVR): No change or an increase in EF, and no focal wall motion abnormalities in response to mental stress testing Mental stress testing resulted in increased platelet aggregation, as measured by the AUC and maximal amplitude, in patients who are susceptible to mental stress induced ischemia Future work should investigate whether or not antiplatelet therapy could be protective against mental stress induced myocardial ischemia in susceptible patients Disclosures: Harrison, RW: None Becker, RC: Honoraria; Bristol-Myers Squibb, Sanofi-Aventis, Boehringer Ingelheim. Research Grants; Bristol-Myers Squibb, Bayer Pharmaceuticals, Johns and Johnson, Regado Biosciences, and AstraZeneca Ortel, JL: Honoraria; Boehringer Ingelheim, Instrumentation Laboratories. Research Grants; Pfizer, Eisai, and GSK Kuchibhatla, M: None Boyle, SH: None Samad, Z: None Velazquez, EJ: Honoraria; Novartis. Speaker’s Bureau; Gilead. Research Grants; Abbott-Vascular Wilson, J: None Kuhn, C: None Williams, RB: Ownership/Partnership/Principal; Williams LifeSkills, Inc. O’Connor, CM: Honoraria; Novella, Cardiology Consulting Associates, Amgen. Ownership/Partnership/ Principal; Biscardia LLC. Research Grants; Otsuka, Roche Diagnostics, BG Medicine, Critical Diagnostics, Astellas, Gilead, GE Healthcare, ResMed Jiang, W: None Sponsorship: National Heart, Lung, and Blood Institute grant number RHL085704 Contact References: 1 Jiang, W. et al Responses of mental stress induced myocardial ischemia to escitalopram treatment: Background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial. Am Heart J. 2012; 163:20-6 2 Jiang W, et al. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease. J Am Coll Cardiol. 2013; 61:714-722