Stress-Related Brain Signals Drive Risk of Cardiovascular Disease in People with Depression and Anxiety

Patients with depression are at higher risk of cardiovascular disease, and a new study suggests that stress may help explain why. Research from Mass General Brigham suggests that this increased risk is driven by stress-related brain activity, nervous system dysregulation, and chronic inflammation. They also found that patients with both depression and anxiety were at even higher risk of cardiovascular disease than those diagnosed with just one condition. The findings, published in Circulation: Cardiovascular Imaging, suggest that stress reduction and related therapeutic targets hold potential for cardiovascular disease prevention.

“These findings give us a clearer biological picture of how emotional distress ‘gets under the skin’ and affects cardiovascular health,” said study first author Shady Abohashem, MD, MPH, an investigator and head of Cardiac PET/CT Imaging Trials at MGH Cardiovascular Imaging Research Center of Massachusetts General Hospital and the Mass General Brigham Heart and Vascular Institute. “For clinicians, it’s a reminder to view mental health as an integral part of cardiovascular risk assessment. For patients, it’s encouragement that addressing chronic stress, anxiety, or depression is not just a mental health priority, it’s also a heart health priority.”

The researchers analyzed data from 85,551 participants in the Mass General Brigham Biobank. Of these, 14,934 presented with both depression and anxiety, 15,819 had either depression or anxiety, and 54,798 had neither condition. Participants were followed for a median of 3.4 years, during which 3,078 experienced major adverse cardiovascular events such as heart attack, heart failure or stroke.

“In line with previous reports, we found that both depression and anxiety were linked to a higher risk of heart attack or stroke,” said senior author Ahmed Tawakol, MD, Director of Nuclear Cardiology at the Mass General Brigham Heart and Vascular Institute. “Notably people who were diagnosed with both depression and anxiety faced roughly a 32% higher risk compared with those diagnosed with only one condition. Importantly, these associations remained strong even after accounting for differences in lifestyle behaviors, socioeconomic factors, and traditional risk factors such as smoking, diabetes, and hypertension.”

To investigate whether depression and anxiety might be linked to heart health via systemic stress responses, the researchers also analyzed advanced brain imaging data and biomarkers of nervous system activity and inflammation for a subset of the participants. They found that people diagnosed with depression or anxiety showed increased activity in the amygdala (a brain region associated with stress), reduced heart rate variability (a sign of an overactive nervous system), and higher blood levels of CRP (a protein linked to inflammation).

“Together, these changes seem to form a biological chain linking emotional stress to cardiovascular risk,” said Abohashem. “When the brain’s stress circuits are overactive, they can chronically trigger the body’s ‘fight or flight’ system, leading to increased heart rate, blood pressure, and chronic inflammation. Over time, these changes can damage blood vessels and accelerate heart disease. This reinforces that protecting heart health isn’t just about diet or exercise, it’s also about emotional health.”

Because the study was based on observational data, more research is needed to determine whether depression and anxiety are causing cardiovascular disease or whether they are simply associated. The researchers are now studying whether interventions such as stress-reduction therapies, anti-inflammatory medications, or lifestyle changes can help normalize these brain and immune markers and, in turn, lower heart risk.

Authorship: In addition to Abohashem and Tawakol, Mass General Brigham authors include Iqra Qamar, Simran S. Grewal, Giovanni Civieri, Sabeeh Islam, Wesam Aldosoky, Sandeep Bollepalli, Rachel P. Rosovsky, Antonia V. Seligowski, Lisa M. Shine, Antonis A. Armoundas, and Michael T Osborne.

Disclosures: Osborne receives consulting fees from WCG Clinical, for unrelated work. Shine receives textbook royalties from Pearson for unrelated work. Remaining authors have no significant disclosures.

Funding: Abohashem is supported in part by the American Heart Association Second Century Faculty Early Independence Award (https://doi.org/10.58275/AHA.24SCEFIA1256969.pc.gr.193937). Tawakol is supported by NIH P01HL131478. Seligowski is supported by NIH K23MH125920. MTO is supported by NIH K23HL151909 and AHA 23SCISA1143491. Armoundas is funded by the Institute of Precision Medicine (17UNPG33840017) of the American Heart Association, the RICBAC Foundation, NIH grants R01 HL135335-01, R01 HL161008-01, R21 HL137870-01, R21EB026164-01 and 3R21EB026164-02S1.

Paper cited: Abohashem, S et al. “Depression and Anxiety Associate with Adverse Cardiovascular Events via Neural, Autonomic and Inflammatory Pathways” Circulation: Cardiovascular Imaging DOI: 10.1161/CIRCIMAGING.124.017706