Ahmed Tawakol1, Michael T Osborne2, Ying Wang3, Basma Hammed4, Brian Tung4, Tomas Patrich4, Blake Oberfeld4, Amorina Ishai4, Lisa M Shin5, Matthias Nahrendorf6, Erica T Warner7, Jason Wasfy8, Zahi A Fayad9, Karestan Koenen10, Paul M Ridker11, Roger K Pitman12, Katrina A Armstrong13. 1. Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: atawakol@mgh.harvard.edu. 2. Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nuclear Medicine, the First Hospital of China Medical University, Heping District, Shenyang, China. 4. Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 5. Department of Psychology, Tufts University, Medford, Massachusetts. 6. Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 7. Clinical Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 8. Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 9. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 10. Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 11. Cardiology Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 12. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 13. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood. OBJECTIVES: Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE. METHODS: A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated 18F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated. RESULTS: Over a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: -0.157 [95% confidence interval (CI): -0.266 to -0.041]; p = 0.007) and arterial inflammation (β: -0.10 [95% CI: -0.18 to -0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: -0.01 [95% CI: -0.06 to -0.001]; p < 0.05). CONCLUSIONS: Lower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.
BACKGROUND: Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood. OBJECTIVES: Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE. METHODS: A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated 18F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated. RESULTS: Over a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: -0.157 [95% confidence interval (CI): -0.266 to -0.041]; p = 0.007) and arterial inflammation (β: -0.10 [95% CI: -0.18 to -0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: -0.01 [95% CI: -0.06 to -0.001]; p < 0.05). CONCLUSIONS: Lower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.
Authors: J Douglas Bremner; Eric Vermetten; Christian Schmahl; Viola Vaccarino; Meena Vythilingam; Nadeem Afzal; Christian Grillon; Dennis S Charney Journal: Psychol Med Date: 2005-06 Impact factor: 7.723
Authors: Lisa M Shin; Christopher I Wright; Paul A Cannistraro; Michelle M Wedig; Katherine McMullin; Brian Martis; Michael L Macklin; Natasha B Lasko; Sarah R Cavanagh; Terri S Krangel; Scott P Orr; Roger K Pitman; Paul J Whalen; Scott L Rauch Journal: Arch Gen Psychiatry Date: 2005-03
Authors: Sameed Ahmed M Khatana; Atheendar S Venkataramani; Ashwin S Nathan; Elias J Dayoub; Lauren A Eberly; Dhruv S Kazi; Robert W Yeh; Nandita Mitra; S V Subramanian; Peter W Groeneveld Journal: JAMA Date: 2021-02-02 Impact factor: 56.272
Authors: Stephen Y Wang; Andy S L Tan; Brian Claggett; Alvin Chandra; Sameed Ahmed M Khatana; Pamela L Lutsey; Anna Kucharska-Newton; Silvia Koton; Scott D Solomon; Ichiro Kawachi Journal: JAMA Cardiol Date: 2019-12-01 Impact factor: 14.676
Authors: Eric D Finegood; Edith Chen; Jennifer Kish; Katherine Vause; Adam K K Leigh; Lauren Hoffer; Gregory E Miller Journal: Psychoneuroendocrinology Date: 2020-02-19 Impact factor: 4.905
Authors: Michael T Osborne; Lisa M Shin; Nehal N Mehta; Roger K Pitman; Zahi A Fayad; Ahmed Tawakol Journal: Circ Cardiovasc Imaging Date: 2020-08-14 Impact factor: 7.792
Authors: Tawseef Dar; Michael T Osborne; Shady Abohashem; Taimur Abbasi; Karmel W Choi; Ahmed Ghoneem; Nicki Naddaf; Jordan W Smoller; Roger K Pitman; John W Denninger; Lisa M Shin; Gregory Fricchione; Ahmed Tawakol Journal: Circ Cardiovasc Imaging Date: 2020-08-13 Impact factor: 7.792
Authors: Sundus S Lateef; Mina Al Najafi; Amit K Dey; Mariyam Batool; Khaled M Abdelrahman; Domingo E Uceda; Aarthi S Reddy; Maryia D Svirydava; Navya Nanda; Jenis E Ortiz; Nina Prakash; Justin A Rodante; Andrew Keel; Wunan Zhou; Marcus Y Chen; Martin P Playford; Heather L Teague; Ahmed A Tawakol; Joel M Gelfand; Tiffany M Powell-Wiley; Nehal N Mehta Journal: Atherosclerosis Date: 2020-07-29 Impact factor: 5.162