- Chronic stress has long been associated with increased risk of atherosclerotic cardiovascular disease
- At Massachusetts General Hospital, multi-organ, multimodality imaging has provided critical insights into the heart–brain link by uncovering a neuroimmune pathway that upregulates inflammation and culminates in major adverse cardiovascular events
- Common stressors, such as chronic noise exposure and income disparities, have been found to drive the front end of this neuroimmune pathway
- The findings suggest several novel targets have the potential to attenuate cardiovascular pathology secondary to chronic stress
- Clinicians should stay aware of the pro-inflammatory role of chronic stress in individuals with CVD
Chronic psychosocial stress has been linked in several large studies with increased risk of cardiovascular disease (CVD), on a par with traditional risk factors. However, most clinical guidelines for managing CVD don't mention chronic stress, largely because there's limited understanding of how it's linked to CVD pathophysiologically.
Researchers at Massachusetts General Hospital have been investigating this question for years, and they recently reviewed their key findings in the Journal of Nuclear Cardiology. The authors are Michael T. Osborne, MD, an assistant in medicine in the Cardiology Division at Mass General, Ahmed Tawakol, MD, co-director of the Cardiac MR PET CT Program in the Cardiology Division, and colleagues in both the Cardiology Division and the Cardiovascular Imaging Research Center at Mass General: Shady Abohashem, MD, Hadil Zureigat, MD, and Taimur A. Abbasi, MD.
A Role for the Amygdala?
Chronic stress is known to activate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). The amygdala has inputs to the HPA axis, SNS and other brain regions, and it plays a critical role in emotional and physical response to stress.
Therefore, Mass General researchers hypothesized that the amygdala may play a critical role at the front end of the pathway linking chronic stress to CVD. They used multi-tissue positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) to investigate. Amygdalar 18F-FDG uptake (AmygA) has been shown to be heightened in humans with stress conditions (e.g., post-traumatic stress disorder).
Multiorgan Neuroimmune Pathway Links Stress to CVD
The researchers showed that:
- In a prospective cohort of individuals with diagnosed stress conditions, scores on the Perceived Stress Scale were significantly associated with AmygA, C-reactive protein (a measure of inflammation) and an 18F-FDG-PET imaging index of arterial inflammation (ArtI)
- In a retrospective cohort of individuals without CVD who were followed for up to five years, AmygA was independently associated with bone marrow activity (i.e., leukopoietic activity) as well as ArtI and CVD events
- Heightened AmygA→ increased bone marrow activity→ increased ArtI→ increased CVD events, supporting a multiorgan neuroimmune pathway that links stress to atherosclerotic CVD
Common Stressors Drive the Front End of the Pathway
More recently, Mass General researchers used multiorgan 18F-FDG-PET/CT to study several potential upstream drivers of the neuroimmune mechanism: adverse socioeconomic status and noise exposure. In the Journal of the American College of Cardiology, The researchers reported that low neighborhood income→ increased AmygA→ increased bone marrow activity→ increased ArtI→ increased CVD events.
Similarly, the researchers reported greater exposure to transportation noise→ increased AmygA→ increased ArtI→ increased CVD events.
The neuroimmune mechanism could potentially be attenuated by:
- Strategies that modify the brain—stress reduction techniques (e.g., exercise, yoga), cognitive–behavioral therapy or antidepressants
- Reduction of leukopoiesis, inflammatory gene expression, ArtI, or myocardial blood flow—for instance, beta-blockers may reduce the pro-inflammatory consequences of SNS activity, and statins or anti-inflammatory drugs may have a downstream impact on leukopoietic activity and ArtI
- Lifestyle modifications that reduce stress and inflammation (e.g., improved sleep, increased exercise)
What's clear now is that clinicians should consider treating stress conditions and high levels of stress among individuals with known CVD. For radiologists, this body of work provides exciting evidence that multi-tissue, multimodality imaging can uncover complex disease mechanisms.
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