Mental Stress Score May Pinpoint Stable CAD Patients at Risk for CV Events
A maladaptive stress response might be amenable to behavioral or other interventions to lower future CV risk, say researchers.
A new risk score based on psychological response to stressful situations can identify individuals with stable CAD who are at increased risk for adverse events, and even goes a step beyond traditional risk factor assessment.
Being able to capture this physiologic response to stress adds to researchers’ understanding of how maladaptive responses to stressful events can set off negative hemodynamic and vascular mechanisms in some individuals, lead author Kasra Moazzami, MD, MPH (Emory University School of Medicine, Atlanta, GA), told TCTMD.
“What we’ve developed is this standardized mental stress protocol, which is similar to an exercise stress test. It’s not as straightforward, but it’s a work in progress. The ultimate goal is to use it in a clinic similar to an exercise stress test,” he added. “By understanding those dynamic changes, we understand which patients are more at risk versus those that may not be.”
In prior work, the same researchers demonstrated that ischemia induced by mental stress is an important prognostic indicator that increases the risk of subsequent coronary events, including death. They also have identified three CV reactivity indices that appear to be independently associated with incident CV outcomes: blunted hemodynamic reactivity, endothelial dysfunction, and greater degree of peripheral vasoconstriction.
The new study, published January 23, 2025, in the Journal of the American Heart Association, moves the needle further by combining the three indices into a risk score and testing its prognostic ability.
Tying Stress to Outcome Events
For their study, Moazzami and colleagues pooled data from 629 stable CAD 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. The mean age was 63 years in the MIPS cohort and 51 years in the MIMS2 cohort, with 20% and 50% women, respectively. Notably, the MIMS2 cohort included 65% Black patients.
Myocardial perfusion imaging was performed during standard exercise or physiologic stress testing, as well as during a public speaking task to elicit mental stress. Patients were given 2 minutes to prepare a speech and 3 minutes to deliver it in front of an audience wearing white coats. They were told that the speech would be evaluated for content and duration.
Blood pressure and heart rate were measured during the mental stress challenge. The researchers also calculated hemodynamic response as measured by changes in rate-pressure product (RPP). Changes in endothelial function and vasoconstriction were evaluated during the mental stress testing via brachial artery flow-mediated vasodilation and peripheral arterial tonometry.
The researchers then calculated a cardiovascular reactivity risk (CRR) score for each patient that ranged from 0 to 9. Depression was separately evaluated with the Beck Depression Inventory II, general stress with the 10-item Cohen Perceived Stress Scale, and anxiety with the Spielberger State-Trait Anxiety Inventory.
The MIPS participants were followed for a median of 6 years, during which time the composite endpoint of incident CV death, nonfatal MI, or heart failure hospitalization occurred in 20.9%. Similarly, the MIMS2 participants were followed for a median of 4.5 years, with a composite endpoint rate of 24.3%.
When all three cardiovascular reactivity indices were included in the fully adjusted model, they were each independently associated with outcomes in both cohorts. The magnitude of the association was greatest for blunted hemodynamic response, followed by worsening endothelial function, and greater peripheral vasoconstriction.
The mean CRR score was 4.5 in the MIPS participants and 4.4 in the MIMS2 cohort. On multivariable analysis, a higher score was significantly associated with a higher body mass index and history of heart failure.
Analyses that adjusted for demographic, clinical, and psychological characteristics and medications found that for every unit increase in the CRR score, there was an 18% increase in the hazard of future events in MIPS participants and a 15% increase for MIMS2 participants. In sensitivity analyses, the association between RPP reactivity with mental stress and the risk of future events was similar regardless of age, sex, race, and clinical characteristics.
To TCTMD, Moazzami noted that adding the CRR score to a statistical model with baseline demographics and traditional and psychosocial risk factors increased the prediction C-statistic by 10%.
What Happens Next?
The data thus far on CV reactivity to mental stress “opens the door” for future research into mechanisms for normalizing stress responses and potentially reducing adverse outcomes, say researchers.
“One idea is cognitive behavioral therapy [because] we know it helps with stress, we know people feel better, but does that method manipulate or adjust these stress responses? That’s what we’re working on now,” Moazzami said.
Another hurdle will be to standardize the mental stress test for routine clinical use as a complement to exercise stress testing. Moazzami said artificial intelligence may help by having patients wear virtual reality goggles that could simulate being in a public speaking challenge or other stressful interpersonal situation that mimics in a more simplified way what the MIPS and MIMS2 participants experienced.
“The goal is not to frighten people or shock them,” he added. “We want to replicate that uncomfortable feeling that people experience in their daily lives that causes them stress [and that is] relatable and something we can use on a large scale.”
Taken together, this research is aiming for a type of personalized risk assessment, Moazzami noted.
“Rather than encouraging stress reduction in everyone, this would help us choose modalities for specific people who have a higher risk based on their maladaptive stress responses and see if that makes a difference,” he said.
L.A. McKeown is a Senior Medical Journalist for TCTMD, the Section Editor of CV Team Forum, and Senior Medical…
Read Full BioSources
Moazzami K, Sullivan S, Wang M, et al. Cardiovascular reactivity to mental stress and adverse cardiovascular outcomes in patients with coronary artery disease. J Am Heart Assoc. 2025;13:e034683.
Disclosures
- Moazzami reports no relevant conflicts of interest.
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