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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
ConclusionsRobert W. Harrison, MDDuke Clinical Research InstituteDurham, NC [email protected]
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
MSIMIN=105
P-value
Demographics
Age, mean (SD), years 61.2 (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
Diabetes 16 (32.7) 28 (26.7) 0.44
Current Angina 10 (20.4) 22 (21.0) 0.95
Prior Myocardial Infarction
15 (30.6) 53 (50.5) 0.07
Prior PCI 28 (57.1) 65 (61.9) 0.57
Prior CABG 22 (44.9) 52 (49.5) 0.59
Congestive Heart Failure 1 (2.0) 7 (6.67) 0.23
Hypertension 38 (77.6) 79 (75.2) 0.75
Hyperlipidemia 47 (95.9) 97 (92.4) 0.41
Current Tobacco Use 4 (8.2) 19 (18.1) 0.27
Depression 5 (10.2) 19 (18.1) 0.21
Baseline Ejection Fraction, mean (SD), %
55.5 (8.7) 53.3 (11.0) 0.21
Medications
Aspirin 47 (95.9) 102 (98.1) 0.44
Additional Antiplatelet 20 (40.8) 49 (47.1) 0.47
ACE-I 35 (71.4) 69 (66.4) 0.53
ARB 3 (6.1) 16 (15.4) 0.11
Calcium Channel Blocker 9 (18.8) 18 (17.3) 0.83
Beta blocker 38 (77.6) 93 (89.4) 0.051
Statin 46 (93.9) 99 (95.2) 0.73
Table 1: Baseline characteristicsAgonist Normal LV
responseN=49
Mean (SD)
MSIMIN=105
Mean (SD)
P-value
Area Under the Curve (% x minutes)
ADP 5 µM 239.1 (127.5) 237.5 (110.0) 0.94
Epinephrine, 10 µM 147.1 (146.0) 139.5 (81.8) 0.73
Collagen, 10 µM 273.1 (102.1) 278.6 (95.6) 0.75
Serotonin, 5 µM+ ADP, 1 µM 211.7 (119.0) 206.0 (105.0) 0.77
Serotonin, 5 µM+ Epinephrine, 2 µM 243.9 (97.3) 242.3 (89.7) 0.92
Serotonin, 5 µM + Collagen, 2 µM 232.1 (107.4) 235.9 (91.3) 0.83
Maximal Amplitude (%)
ADP 5 µM 53.6 (22.4) 52.5 (20.7) 0.77
Epinephrine, 10 µM 28.5 (18.0) 29.6 (15.8) 0.71
Collagen, 10 µM 67.0 (23.1) 66.7 (19.6) 0.93
Serotonin, 5 µM+ ADP, 1 µM 50.0 (20.7) 47.9 (18.7) 0.53
Serotonin, 5 µM+ Epinephrine, 2 µM 53.6 (18.3) 52.5 (18.1) 0.73
Serotonin, 5 µM + Collagen, 2 µM 52.0 (23.4) 52.9 (19.9) 0.83
Table 2: Baseline resting platelet aggregation
-60-50-40-30-20-10
010203040
NLVRMSIMI
∆ A
UC
ADP EPI Coll5HT + ADP 5HT + Epi 5HT+ Coll
-12-10-8-6-4-20246
∆ M
ax
ima
l A
mp
litu
de
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
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• Patients with coronary heart disease are susceptible to mental stress-induced myocardial ischemia (MSIMI),
and patients susceptible to MSIMI have a poorer prognosis1
• MSIMI was more common than exercise induced myocardial ischemia in the REMIT trial, affecting 43% of patients with coronary heart disease2
• Patients with MSIMI have a poorer prognosis than those who do not exhibit MSIMI1
• 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 established1
• 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: 1Jiang, 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
2Jiang 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
