Summary: Depression and anxiety may increase the risk of cardiovascular disease through chronic stress pathways in the brain and body. In a large analysis of more than 85,000 adults, those with depression or anxiety (especially both) were significantly more likely to have a heart attack, stroke, or heart failure.
A subset of participants also showed signs of increased amygdala activity, an overactive stress response system, and elevated inflammation, all of which are known to damage blood vessels over time. These findings suggest that emotional health is deeply intertwined with cardiovascular risk and that stress reduction therapies may have both physical and psychological benefits.
Key facts
Emotional stress pathway: Overactive stress circuits, lower heart rate variability, and chronic inflammation linked depression/anxiety to cardiovascular disease. Increased combined risk: People with depression and anxiety had about a 32% higher cardiovascular risk than those with either condition alone. Therapeutic potential: Approaches aimed at reducing stress and inflammation may help reduce future risk of heart disease.
Source: General de Masas
Patients with depression are at increased 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 depression and anxiety had an even higher risk of cardiovascular disease than those diagnosed with a single condition.
The findings, published in Circulation: Cardiovascular Imaging, suggest that stress reduction and related therapeutic targets have potential for the prevention of cardiovascular disease.
“These findings give us a clearer biological picture of how emotional distress ‘gets under the skin’ and impacts cardiovascular health,” said study first author Shady Abohashem, MD, MPH, investigator and head of PET/CT cardiac imaging trials at the MGH Cardiovascular Imaging Research Center at Massachusetts General Hospital and the Brigham General Heart and Vascular Institute at Massachusetts.
“For doctors, it’s a reminder that they should consider mental health as an integral part of cardiovascular risk assessment. For patients, it’s an encouragement to know that addressing chronic stress, anxiety or depression is not only a mental health priority, but also a heart health priority.”
The researchers analyzed data from 85,551 participants in the Mass General Brigham Biobank. Of them, 14,934 had depression and anxiety, 15,819 had depression or anxiety and 54,798 had neither condition. Participants were followed for an average of 3.4 years, during which 3,078 experienced major adverse cardiovascular events, such as heart attack, heart failure or stroke.
“Consistent with previous reports, we found that both depression and anxiety were related to an increased risk of heart attack or stroke,” said lead author Ahmed Tawakol, MD, director of Nuclear Cardiology at Mass General Brigham Heart and Vascular Institute.
“Notably, people diagnosed with depression and anxiety faced approximately 32% increased risk compared to those diagnosed with a single condition. Importantly, these associations remained strong even after accounting for differences in lifestyles, socioeconomic factors, and traditional risk factors such as smoking, diabetes, and hypertension.”
To investigate whether depression and anxiety could be linked to heart health through systemic responses to stress, the researchers also analyzed advanced brain imaging data and biomarkers of nervous system activity and inflammation from a subset of participants.
They found that people diagnosed with depression or anxiety showed increased activity in the amygdala (a region of the brain associated with stress), reduced heart rate variability (a sign of an overactive nervous system), and higher levels of CRP (a protein linked to inflammation) in their blood.
“Together, these changes appear to form a biological chain linking emotional stress to cardiovascular risk,” Abohashem said.
“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 is not just about diet or exercise, but 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 if they are simply associated.
Researchers are now studying whether interventions such as stress-reducing therapies, anti-inflammatory medications, or lifestyle changes can help normalize these brain and immune markers and, in turn, reduce cardiac risk.
Authorship: In addition to Abohashem and Tawakol, Masa Brigham’s General 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. The remaining authors have no significant disclosures.
Funding: Abohashem is supported in part by the American Heart Association Second Century Faculty Early Independence Award. 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 American Heart Association Institute for Precision Medicine (17UNPG33840017), the RICBAC Foundation, NIH grants R01 HL135335-01, R01 HL161008-01, R21 HL137870-01, R21EB026164-01, and 3R21EB026164-02S1.
Key questions answered:
A: The study links depression to overactive brain circuits related to stress, nervous system dysregulation and chronic inflammation, all factors known to accelerate cardiovascular disease.
A: Yes. People diagnosed with both conditions had an approximately 32% increased risk of major cardiovascular events compared to those with only one condition.
A: Increased amygdala activity, reduced heart rate variability, and higher inflammatory markers (such as CRP) formed a stress-related pathway linked to cardiovascular risk.
Editorial notes:
This article was edited by a Neuroscience News editor. Magazine article reviewed in its entirety. Additional context added by our staff.
About this research news on depression and cardiovascular diseases.
Author: Brandon Chase
Source: General de Masas
Contact: Brandon Chase – Mass General
Image: Image is credited to Neuroscience News.
Original Research: Closed access.
“Depression and anxiety are associated with adverse cardiovascular events through neural, autonomic, and inflammatory pathways” by Shady Abohashem et al. Circulation
Abstract
Depression and anxiety are associated with adverse cardiovascular events through neuronal, autonomic and inflammatory pathways
BACKGROUND:
Depression is linked to major adverse cardiac events (MACE), but the role of stress-related neural activity (previously implicated in stress and anxiety) in mediating this association remains unclear. Because anxiety and depression often co-occur and share neurobiological pathways, we hypothesize that the relationship between depression, anxiety, and their co-occurrence with MACE is partially mediated by increased stress-related neural activity and related autonomic-immune mechanisms.
METHODS:
Data were obtained from participants enrolled in the Mass General Brigham Biobank (2010-2020). A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography to assess stress-related neuronal activity, defined as the relationship between the amygdala and background prefrontal cortical activity. Heart rate variability and CRP (C-reactive protein) served as indicators of autonomic activity and systemic inflammation.
Depression and anxiety were determined at enrollment and MACE was identified during follow-up using International Classification of Diseases codes. Each exposure (depression, anxiety, or co-occurring anxiety plus depression) was modeled separately based on study outcomes using linear and Cox regressions.
RESULTS:
Of the 85,551 study subjects, 3,078 (3.6%) participants developed MACE, during a median follow-up of 3.4 years (interquartile range, 1.9–4.8). Depression was associated with an increased risk of MACE (hazard ratio, 1.24 (95% CI, 1.14–1.34); P < 0.001), with stronger associations for concurrent anxiety plus depression (hazard ratio, 1.35 (1.23–1.49); P < 0.001) and remained significant after adjustment for demographic, lifestyle, cardiovascular, and socioeconomic factors.
In subsamples with available imaging (N = 1,123) or biomarkers (heart rate variability, N = 7,862; CRP, N = 12,906), depression was associated with a higher ratio of amygdala to cortical activity (β = 0.16; P = 0.006), lower heart rate variability (β = −0.20; P < 0.001), and a higher CRP high (β = 0.14; P<0.001). Mediation analyzes showed indirect effects of amygdala-to-cortex activity ratio, heart rate variability, and CRP on the depression-MACE relationship (log odds ratios, 0.04, 0.04, and 0.02, respectively; all P < 0.05). Similar associations were observed for anxiety or anxiety plus concurrent depression.
CONCLUSIONS:
Depression and anxiety are independently associated with increased risk of MACE, partly mediated by increased stress-related neural activity and autonomic-immune dysregulation. The risk is highest among those with both conditions, underscoring the shared pathophysiology related to stress.
