Mental Stress and Myocardial Ischemia After MI: Sex Differences, Mechanisms and Prognosis

In the U.S. and globally, coronary heart disease (CHD) is the number one killer of women. Despite scientific advances, it is unclear whether the pathophysiology of CHD differs between women and men. The study of CHD in women has historically been centered on older women; however, women with early-onset CHD are informative for the study of early risk factors and pathophysiology. Furthermore, young women with a myocardial infarction (MI) have emerged as a group in need of special study, as this group has higher mortality compared with men of similar age despite less severe disease. These disparities remain unexplained and suggest sex differences in the pathophysiology, risk factors, and prognostic factors of acute MI.

The psychosocial sphere is a largely neglected area for CHD prevention in women. Social and emotional exposures, mostly beginning early in life (depression, early life adversities, poverty, and posttraumatic stress symptoms), are more common in younger women with MI compared with men and community controls. In addition to being more prevalent, emotional stress may be a stronger risk factor in young women than in other groups. A significant challenge, however, is to measure stress validly.

Building on previous work, the current project will clarify sex differences in pathways of risk linking emotional stress to mental stress-induced myocardial ischemia (MSI) and cardiovascular outcomes in young post-MI patients. Within 8 months of MI, 310 patients ≤60 years of age (at the time of the MI), 50% women, will be tested in the lab with a stress challenge to assess MSI using an established protocol with myocardial perfusion imaging. Participants will be monitored at home for 1 week and then followed for clinical events for 3 years.

Inclusion criteria

• History of documented MI within the past 8 months
• Age ≤60 at the time of MI

Exclusion criteria

• History of unstable angina, MI, or decompensated heart failure in the past month
• Patients deemed to be unsafe to hold anti-ischemic medications before testing (it is standard protocol to hold these meds before imaging studies)
• Systolic blood pressure (SBP) >180 mm Hg or diastolic blood pressure (DBP) >110 mm Hg on the day of the test
• Alcohol or substance abuse (past year), or severe psychiatric disorder other than major depression
• Other serious medical disorders that may interfere with the study results
• Postmenopausal hormone therapy (past 3 months)
• Current psychotropic medications (past month) except anti-depressants
• Pregnancy or breastfeeding (all women will receive a pregnancy test)
• Severe aortic stenosis
• Weight ≥ 360 pounds and/or body mass index (BMI) of 40 or greater (weight limit of the SPECT imaging table)