Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease

Background: The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease. Methods: Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire’s angina frequency subscale at baseline and 2 years follow-up. Results: We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ( , 13.7 [95% CI, 6.3–21.7]; P =0.008) and 11.6 units during follow-up ( , 11.6 [95% CI, 4.1–19.2]; P =0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively. Conclusions: Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.