Brain activity during stress may predict angina in CAD – Healio

August 10, 2020

2 min read

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Inferior frontal lobe activation caused in addition to mental stress was independently linked to angina at baseline and during 2-year follow-up, researchers found.

Amit J. Shah

“These findings provide experimental biological evidence that the brain plays an important role in angina, and shifts the focus away from blood flow to the heart,” Amit J. Shah, MD, MSCR, assistant professor of epidemiology at Emory University Rollins School of Public Health, told Healio. “Although the relationship between depression and angina were already known, the missing link was the biological underpinning to this relationship. We now have greater understanding of the potential brain pathways involved in angina.”

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Patients with CAD

In this study published in Circulation: Cardiovascular Imaging, Kasra Moazzami, MD, MPH, MSCR, fellow at the Clinical Cardiovascular Research Institute at Emory University, and colleagues analyzed data from 148 patients (mean age, 62 years; 69% men) with CAD between June 2011 and August 2014. Several measures were taken to assess depressive symptoms, PTSD symptoms, anxiety, distress and functional capacity. Mental stress testing was also performed with myocardial perfusion imaging and high-resolution PET brain imaging. Angina symptoms were analyzed with the Seattle Angina Questionnaire’s angina frequency subscale at baseline and at 2 years.

“Angina is one of the most common and concerning patient complaints, impairs quality of life and associates with higher mortality risk,” Shah said in an interview. “Unfortunately, in many cases, our treatment options are limited. We had preliminary evidence that stress could be a major underlying reason for this, and as the next step, studied stress reactivity in the inferior frontal lobe of the brain and its relationship with angina. This region was, in particular, studied because of previous studies revealing a strong relationship with stress and heart disease.”

Angina frequency increased by 13.71 units at baseline (beta = 13.7; P = .008) for every doubling in inferior frontal lobe activation after adjusting for lifestyle and sociodemographic characteristics. This increase was also observed at 2 years (11.6 units; beta = 11.6; P = .01).

Ischemia induced by mental stress accounted for 40% of the total effect of inferior frontal lobe activation on the severity of angina at baseline. In addition, activation of other brain pain processing regions including the insula, thalamus and amygdala described 13.1% of this effect on angina severity, the researchers wrote.

Chest pain and psychological stress

“The implications on clinical practice are potentially profound considering this study and the body of evidence upon which it builds that have supported stress as a major risk factor for chest pain,” Shah told Healio. “The general take-home point is that providers should broaden their focus when approaching chest pain and inquire about psychological stress. Although our study does not test a particular intervention, it does shed light on a mechanistic pathway (brain-heart) that is often ignored. Normally, providers order a conventional stress test for angina as the first test. Surprisingly, this was not related to angina in our study.”


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Amit J. Shah, MD, MSCR, can be reached at

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