Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: Insights from the REMIT study

Abstract

Background Although emotional stress is associated with ischemic heart disease (IHD) and related clinicalevents, sex-specific differences in the psychobiological response to mental stress have not been clearly identified. Objectives We aimed to study the differential psychological and cardiovascular responses to mental stressbetween male and female patients with stable IHD. Methods Patients with stable IHD enrolled in the REMIT (Responses of Mental StressInduced Myocardial Ischemiato Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregationstudies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was definedas the development or worsening of regional wall motion abnormality, reduction of left ventricular ejection fraction(LVEF) ≥8% by transthoracic echocardiography, and/or ischemic ST-segment change on electrocardiogram during1 or more of the 3 mental stress tasks. Results In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similarbetween women and men (including heart rate, blood pressure, and LVEF), although women were more likely to benonwhite, living alone (p < 0.001), and unmarried (p < 0.001); they also had higher baseline depression and anxiety(p < 0.05). At rest, women had heightened platelet aggregation responses to serotonin (p = 0.007) and epinephrine(p = 0.004) compared with men. Following mental stress, women had more MSIMI (57% vs. 41%; p < 0.04), expressedmore negative (p = 0.02) and less positive emotion (p < 0.001), and demonstrated higher collagen-stimulated plateletaggregation responses (p = 0.04) than men. Men were more likely than women to show changes in traditional physiologicalmeasures, such as blood pressure (p < 0.05) and double product. Conclusions In this exploratory analysis, we identified clear, measurable, and differential responses to mentalstress in women and men. Further studies should test the association of sex differences in cardiovascular andplatelet reactivity in response to mental stress and long-term outcomes. (Responses of Myocardial Ischemia toEscitalopram Treatment [REMIT]; NCT00574847) (J Am Coll Cardiol 2014;64:166978).