Muhammad Hammadah1, Samaah Sullivan2, Brad Pearce2, Ibhar Al Mheid1, Kobina Wilmot1, Ronnie Ramadan1, Ayman Samman Tahhan1, Wesley T O'Neal1, Malik Obideen1, Ayman Alkhoder1, Naser Abdelhadi1, Heval Mohamed Kelli1, Mohamad Mazen Ghafeer1, Pratik Pimple2, Pratik Sandesara1, Amit J Shah3, Kareem Mohammed Hosny1, Laura Ward2, Yi-An Ko2, Yan V Sun2, Lei Weng2, Michael Kutner4, J Douglas Bremner5, David S Sheps6, Fabio Esteves7, Paolo Raggi8, Viola Vaccarino9, Arshed A Quyyumi10. 1. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. 2. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States. 3. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States; Atlanta VA Medical Center, Decatur, GA, United States. 4. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United States. 5. Atlanta VA Medical Center, Decatur, GA, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. 6. University of Florida Health Science Center, Department of Medicine, Division of Cardiovascular Medicine, Gainesville, FL, United States. 7. Department of Radiology, Emory University School of Medicine, Atlanta, GA, United States. 8. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States; Department of Radiology, Emory University School of Medicine, Atlanta, GA, United States; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. 9. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States. Electronic address: lvaccar@emory.edu. 10. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: aquyyum@emory.edu.
Abstract
BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS: Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. RESULTS: Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION: Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.
BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS:Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarctionpatients. RESULTS: Of 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION: Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.
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