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

• Type of Material: Article
• Authors: Kasra Moazzami, Emory University; Matthew T Wittbrodt, Emory University; Mhmtjamil Alkhalaf, Emory University; Bruno B Lima, Emory University; Jonathon Nye, Emory University; Puja Mehta, Emory University; Arshed Quyyumi, Emory University; Viola Vaccarino, Emory University; Douglas J Bremner, Emory University; Amit Shah, Emory University
• Language: English
• Date: 2020-08-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Wolters Kluwer Health
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCIMAGING.120.010710
• Title of Journal or Parent Work: CIRCULATION-CARDIOVASCULAR IMAGING
• Volume: 13
• Issue: 8
• Start Page: E010710
• End Page: E010710
• Grant/Funding Information: This work was supported by grants P01 HL101398, R01 HL109413, R01HL109413-02S1, R01HL125246, K24HL077506, K24 MH076955, UL1TR000454, KL2TR000455, K23HL127251, and T32HL130025 from the NIH.
• Keywords: MYOCARDIAL-ISCHEMIA; INTERVENTION; PSYCHOMETRIC PROPERTIES; stress, psychological; DEPRESSION; myocardial ischemia; PERCEPTION; Science & Technology; BRAIN; angina pectoris; CHEST-PAIN; QUESTIONNAIRE; Cardiac & Cardiovascular Systems; coronary artery disease; Cardiovascular System & Cardiology; QUALITY-OF-LIFE; Life Sciences & Biomedicine; Radiology, Nuclear Medicine & Medical Imaging; METAANALYSIS

Abstract

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.