Mental Stress-Induced Ischemia Increases Risk of Poor Outcomes Post-MI

Myocardial ischemia caused by ramped-up psychological stress is associated with poor clinical outcomes in patients who have previously had a myocardial infarction, new study results show.

The research, originally selected for presentation at the American College of Cardiology 2020 Scientific Session that has since converted to a virtual meeting due to the continuing threat of COVID-19, suggests psychological or emotional stress should be an important consideration in selective post-MI patients vulnerable to mental stress-induced ischemia.

“Our study is really powerful in demonstrating, experimentally, that [psychological] stress has really bad consequences for post-MI patients,” said senior investigator Viola Vaccarino, MD, PhD (Emory University Rollins School of Public Health, Atlanta, GA), during a press briefing announcing the results. While only 16% of patients developed ischemia during a public speaking task orchestrated to increase stress levels, these patients had much worse outcomes than those who did not, she said.

To TCTMD, Vaccarino pointed out that they are still a long way from testing how patients may respond to psychological stress in the clinic. “Most likely, the protocol that we were using in our research was too long and too complicated to be done in a feasible fashion in a clinical setting,” she said. “But we are working on it, on creating and developing methods that are simpler and can be used clinically to show a patient’s reactivity to stress.”

Psychological Stress as a Trigger for Acute Events

In research settings, mental stress-induced ischemia provoked by an “acute psychological stress” as opposed to a physical stressor has been observed in anywhere from 15% to 50% of cardiac patients. “It tends to be clinically silent and is generally not related to the severity of atherosclerotic plaques,” said Vaccarino. “It can also occur in the absence of conventional stress ischemia.”

During the media briefing, Vaccarino said previous research has implicated psychological stress not only as a trigger of acute coronary events, but also as a prognostic indicator in cardiac patients. The association between psychological stress and adverse clinical outcomes is independent of other prognostic indicators, as well as traditional cardiovascular risk factors, but the mechanism is currently unclear. Little is known about mental stress-induced ischemia following myocardial infarction and its role in prognosis, she said.

To address the question, the researchers studied 306 patients, 65% of whom were African-American and half of whom were women, with a previous myocardial infarction in the past 8 months in the Myocardial Infarction and Mental Stress Ischemia Study 2 (MIMS-2). Mean age was 50 years. All patients underwent myocardial perfusion imaging with single-photon emission computerized tomography as part of a conventional stress test and during a standardized public speaking task.  

After resting for 30 minutes in a quiet room, mental stress was induced in patients by asking them to imagine a real-life stressful situation, such as a relative being mistreated in a nursing home, and then asked to make up a story around the situation. The patients then delivered the speech in front of an audience wearing white coats and were told that this audience would evaluate their speech for content, quality, and duration. The patient was injected with sestamibi radiolabeled with technetium-99m during the public speech for perfusion imaging.

Over a median follow-up of 3 years, the primary endpoint, a composite of cardiovascular death or recurrent nonfatal MI, occurred in 20% of patients with ischemia during the public speaking task compared with 8% of patients without myocardial ischemia during the speech. In the unadjusted analysis, those with mental stress-induced ischemia had a significantly elevated risk of cardiovascular death or recurrent nonfatal MI compared with those without such ischemia (HR 2.6; 95% CI 1.2-5.6). Even after adjusting for demographics, clinical risk factors, and various psychosocial factors, the association remained unchanged and statistically significant. There was no difference in the rates of coronary revascularization between those with and without mental stress-induced ischemia.

Comparatively, myocardial ischemia on conventional stress testing, which was evident in 26% of patients, was not associated with an increased risk of the primary endpoint (HR 1.4; 95% CI 0.6-3.0) and did not explain the association of mental stress-induced ischemia with outcomes, say researchers.

Vaccarino said that patients with myocardial ischemia on conventional stress testing were more likely to have obstructive CAD on coronary catheterization compared with those without ischemia during the conventional stress testing. In contrast, “there was no association with mental stress-induced ischemia with obstructive coronary artery disease,” she said. This is more evidence that the “mechanisms underlying mental stress-induced ischemia are different from traditional ischemia and that potentially microvascular function could be a factor,” said Vaccarino.  

She added that women were nearly twice as likely to developed mental stress-induced ischemia as men, but there was no difference in outcomes when analyzed by sex.