MedicalResearch.com Interview with:
Dr Ahmed Tawakol MD
Co-Director, Cardiac MR PET CT Program
Massachusetts General Hospital and
Harvard Medical School
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: While the link between stress and heart disease has long been established, the mechanism mediating that risk hasn’t been clearly understood. Animal studies showed that stress activates bone marrow to produce white blood cells, leading to arterial inflammation. This study suggests an analogous path exists in humans. Moreover, this study identifies, for the first time in animal models or humans, the region of the brain (the amygdala) that links stress to the risk of heart attack and stroke.
The paper reports on two complementary studies.
The first analyzed imaging and medical records data from almost 300 individuals who had PET/CT brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that both measures the activity of areas within the brain and reflects inflammation within arteries. All participants in that study had no active cancer or cardiovascular disease at the time of imaging and each had information in their medical records on at least three additional clinical visits after imaging.
The second study enrolled 13 individuals with a history of post-traumatic stress disorder, who were evaluated for their current levels of perceived stress and received FDG-PET scanning to measure both amygdala activity and arterial inflammation.
MedicalResearch.com: What are the main findings?
Response: Among participants in the larger, longitudinal study, 22 experienced a cardiovascular disease event — such as a heart attack, stroke or angina episodes — in the follow-up period; and the prior level of activity in the amygdala strongly predicted the risk of a subsequent cardiovascular event. That association remained significant after controlling for traditional cardiovascular risk factors, and after controlling for presence of sub-clinical atherosclerosis at the time of imaging. The association became even stronger when a more stringent definition of cardiovascular events- major adverse cardiovascular events- was used. Amygdalar activity was also associated with the timing of events, as those with the highest levels of activity had events sooner than those with less extreme elevation.
Greater amygdalar activity was also linked to elevated activity of the blood-cell-forming tissue in the bone marrow and spleen and to increased arterial inflammation. In the smaller study, participants’ current stress levels were strongly associated with both amygdalar activity and arterial inflammation.
MedicalResearch.com: What should readers take away from your report?
Response: This study provides more evidence of a heart-brain connection, by elucidating a link between resting metabolic activity in the amygdala, a marker of stress, and subsequent cardiovascular events independently of established cardiovascular risk factors. We also show that amygdalar activity is related to increased associated perceived stress and to an increased vascular inflammation and hematopoietic activity. These findings suggest several potential opportunities to reduce cardiovascular risk attributable to stress, though data demonstrating a benefit of such interventions still need to be developed. In the meantime, it’s reasonable to advise individuals with increased risk of cardiovascular disease to consider employing stress-reduction approaches if they feel subjected to a high degree of psychosocial stress.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Large trials are needed to assess whether stress reduction improves cardiovascular disease risk. Further, pharmacological manipulation of the amygdalar-bone marrow-arterial axis may provide new opportunities to reduce cardiovascular disease. In addition, increased stress associates with other diseases, such as cancer and inflammatory conditions (including rheumatoid arthritis and psoriasis). So, it will be important to evaluate whether calming this stress mechanism produces benefits in those diseases as well.
Disclosures: The study was partially funded by the National Heart, Lung, and Blood Institute and was conducted by scientists from Massachusetts General Hospital and Harvard Medical School, Cornell Medical College, Icahn School of Medicine at Mount Sinai and Tufts University.
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Citation:Ahmed Tawakol, Amorina Ishai, Richard AP Takx, Amparo L Figueroa, Abdelrahman Ali, Yannick Kaiser, Quynh A Truong, Chloe JE Solomon, Claudia Calcagno, Venkatesh Mani, Cheuk Y Tang, Willem JM Mulder, James W Murrough, Udo Hoffmann, Matthias Nahrendorf, Lisa M Shin, Zahi A Fayad, Roger K Pitman. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. The Lancet, 2017; DOI: 10.1016/S0140-6736(16)31714-7
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