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

J Am Coll Cardiol. 2014 Oct 21;64(16):1669-78. doi: 10.1016/j.jacc.2014.04.087.

Abstract

Background: Although emotional stress is associated with ischemic heart disease (IHD) and related clinical events, 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 stress between male and female patients with stable IHD.

Methods: Patients with stable IHD enrolled in the REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregation studies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was defined as 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 during 1 or more of the 3 mental stress tasks.

Results: In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similar between women and men (including heart rate, blood pressure, and LVEF), although women were more likely to be nonwhite, 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), expressed more negative (p = 0.02) and less positive emotion (p < 0.001), and demonstrated higher collagen-stimulated platelet aggregation responses (p = 0.04) than men. Men were more likely than women to show changes in traditional physiological measures, such as blood pressure (p < 0.05) and double product.

Conclusions: In this exploratory analysis, we identified clear, measurable, and differential responses to mental stress in women and men. Further studies should test the association of sex differences in cardiovascular and platelet reactivity in response to mental stress and long-term outcomes. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

Keywords: mental stress; myocardial ischemia; women.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antidepressive Agents, Second-Generation / pharmacology
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Citalopram / pharmacology
  • Citalopram / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood*
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / psychology
  • Platelet Activation / drug effects
  • Platelet Activation / physiology*
  • Sex Characteristics*
  • Stress, Psychological / blood*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / psychology
  • Treatment Outcome

Substances

  • Antidepressive Agents, Second-Generation
  • Citalopram

Associated data

  • ClinicalTrials.gov/NCT00574847