Stressed Out Stable CAD Patients Have Higher Risk of MI and CV Death

Mental stress’ negative impact on CV health may be a common and overlooked risk factor in patients with stable CAD, according to pooled registry data.

“We were able to demonstrate that in the current era, ischemia induced by mental stress is an important prognostic indicator, meaning that patients who have this kind of response have a substantial increase in the risk of subsequent coronary events, including death,” Viola Vaccarino, MD, PhD (Emory University, Atlanta, GA), the study’s lead author, told TCTMD.

CAD patients in the study who showed evidence of ischemia induced both by mental stress and by conventional (exercise or pharmacological) stress tests had the highest risks of all.

In an editorial accompanying the study in JAMA, Paco E. Bravo, MD, and Thomas P. Cappola, MD (both Hospital of the University of Pennsylvania, Philadelphia), say the reason for the additive effect may be related to a coexistence of coronary endothelium-dependent and endothelium-independent microvascular dysfunction. That combination may lead to disastrous consequences when an individual with a CAD history is under both psychological and physical stress.

Bravo and Cappola add that the results confirm older observations about the link between mental stress and CAD, which have been largely demonstrated only in small studies that lacked racial, ethnic, and gender diversity, making it “unclear whether the increased risk of cardiac events associated with mental stress-induced myocardial ischemia can be generalized to larger populations with CHD.” In contrast, one-third of the patients in Vaccarino’s analysis were women and 40% were Black.

The American Heart Association recently released a scientific statement noting that stress is an established trigger for acute events after an initial MI. Also, as reported by TCTMD, earlier research has drawn a connection between childhood trauma and early-onset MI.

MIPS and MIMS2

For their study, Vaccarino and colleagues pooled data from a total of 918 patients who were enrolled in either the Mental Stress Ischemia Prognosis Study (MIPS) or the Myocardial Infarction and Mental Stress Study 2 (MIMS2), which had similar research protocols and were conducted in parallel between June 2011 and March 2016.

Myocardial perfusion imaging was performed during standard exercise or physiologic stress testing, as well as during a public speaking task designed to elicit mental stress. For the task, patients were given 2 minutes to prepare a speech using a scenario in which a relative had been mistreated in a nursing home. They then had 3 minutes to deliver the speech in front of an audience wearing white coats and were told that the speech would be evaluated for content and duration.

Overall, mental stress-induced ischemia occurred in 16% of patients, conventional stress ischemia in 31%, and both types of ischemia in 10%.

At a median follow-up of 5 years, patients with versus without mental stress-induced ischemia had a higher rate of CV death or MI (adjusted HR 2.5; 95% CI 1.8-3.5), as well as a higher rate of the secondary endpoint of HF hospitalization (adjusted HR 2.0; 95% CI 1.5-2.5). The risk of CV death or MI was highest in patients with versus without both mental stress ischemia and conventional stress ischemia (HR 3.8; 95% CI 2.6-5.6), followed by those with mental stress ischemia alone (HR 2.0; 95% CI 1.1-3.7). Conventional stress ischemia alone, however, was not associated with the primary endpoint (HR 1.4; 95%CI 0.9-2.1). The results were consistent in several different models.

Is It Modifiable?

“The fact that mental stress was an independent predictor of events, and actually even stronger in terms of effect than conventional stress-induced ischemia, adds to our understanding of ischemia in general,” Vaccarino said.

The next steps in this research include figuring out how the findings can be clinically useful, she added. “Even though we don't have a clear answer about how to do this in clinical practice today, we hope that at least we can make people in the medical community, as well as patients, aware of how important stress is, and stress responses are, in terms of future events.”

Among important future questions, note Bravo and Cappola, are the extent to which mental-stress ischemia is therapeutically modifiable, and whether screening for and treating it improves outcomes. “Answers to these important questions will help determine whether mental stress should become an actionable clinical item in the management of individuals with known or suspected coronary heart disease,” they write in their editorial.

To TCTMD, Vaccarino said practice guidelines and preventive management traditionally focus on CV risk factors, with little mention of mental health and the importance of helping patients with these issues.

“Our research highlights that it is important to create a shift in clinical care, particularly in secondary prevention, and presumable also in primary prevention,” she said. “These risk factors that are considered not traditional are very prevalent in the CHD population and they affect patients’ lives tremendously.”