Summary: Depression and anxiety appear to increase the risk of cardiovascular disease through chronic stress pathways that involve the brain, autonomic nervous system, and systemic inflammation. In an analysis of over 85,000 adults, people with depression or anxiety — and particularly those with both conditions — were significantly more likely to experience major cardiovascular events such as heart attack, stroke, or heart failure.
A subset of participants showed elevated activity in the amygdala (a stress-sensitive brain region), signs of autonomic dysregulation such as reduced heart rate variability, and higher levels of inflammatory markers like C-reactive protein (CRP). Together these findings indicate that emotional distress and stress physiology are closely linked to cardiovascular risk, suggesting that stress-reduction and inflammation-targeted strategies may offer both mental and heart health benefits.
Key Facts
- Emotional distress pathway: Overactive stress circuits in the brain, autonomic imbalance, and chronic inflammation connect depression and anxiety to cardiovascular disease.
- Elevated combined risk: Individuals diagnosed with both depression and anxiety had about a 32% higher risk of major cardiovascular events than those with only one condition.
- Therapeutic relevance: Interventions that reduce stress responses or target inflammation may help lower future heart disease risk.
Source: Mass General
Overview
Researchers at Mass General Brigham examined whether stress-related brain activity and accompanying autonomic and immune changes could help explain the well-established link between mood disorders and cardiovascular disease. Their analysis used clinical data, advanced imaging, and inflammatory and autonomic biomarkers to map the biological pathways that may connect emotional distress with heart outcomes.
“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. The results underscore the importance of considering mental health as part of cardiovascular risk assessment and suggest that treating chronic stress, anxiety, or depression may also protect the heart.
The study analyzed 85,551 participants enrolled in the Mass General Brigham Biobank from 2010 to 2020. Of these, 14,934 had both depression and anxiety, 15,819 had either depression or anxiety alone, and 54,798 had neither diagnosis. Participants were followed for a median of 3.4 years, during which 3,078 experienced major adverse cardiovascular events (MACE) including myocardial infarction, heart failure, or stroke.
Senior author Ahmed Tawakol, MD, noted that both depression and anxiety independently associated with increased cardiovascular risk, and that the highest risk occurred in people with both conditions. These associations remained significant even after adjusting for lifestyle factors, socioeconomic status, and traditional cardiovascular risk factors such as smoking, diabetes, and hypertension.
Biological pathways examined
To probe mechanisms linking mood disorders to cardiovascular events, the team evaluated a subset of participants with advanced imaging and laboratory data. In that subset, higher depression or anxiety diagnoses were associated with:
- Increased amygdala activity relative to prefrontal cortex activity (measured by 18F-FDG PET/CT), indicating heightened stress-related neural signaling.
- Lower heart rate variability, reflecting sustained autonomic (sympathetic) activation.
- Elevated CRP levels, a marker of systemic inflammation that contributes to vascular damage over time.
Mediation analyses suggested that these neural, autonomic, and inflammatory markers partially explain the link between emotional distress and subsequent cardiovascular events, supporting a chain of biological responses that connects mental health to heart disease.
Implications and next steps
Because this study is observational, it cannot prove causation; depression and anxiety may be causal contributors to cardiovascular disease or markers of other underlying risks. Nonetheless, the results strengthen the biological rationale for testing whether interventions that lower stress-related brain activity, improve autonomic balance, or reduce inflammation can reduce cardiovascular risk.
Ongoing research will evaluate whether targeted therapies — including stress-reduction programs, behavioral interventions, anti-inflammatory treatments, or lifestyle changes — can normalize these brain and immune signals and in turn lower rates of heart attack, heart failure, and stroke among people with depression and anxiety.
Authorship and disclosures
In addition to Shady Abohashem and Ahmed Tawakol, 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. Osborne receives consulting fees from WCG Clinical for unrelated work; Shine receives unrelated textbook royalties. Other authors report no significant disclosures. Funding support included awards from the American Heart Association and NIH grants acknowledged by the investigators.
Key questions answered
A: The study links depression to overactive stress-related brain circuits, autonomic dysregulation (lower heart rate variability), and chronic inflammation — factors that can accelerate vascular injury and cardiovascular disease.
A: Yes. Individuals diagnosed with both conditions had about a 32% higher risk of major cardiovascular events compared with those diagnosed with only one condition.
A: Increased amygdala activity, reduced heart rate variability, and higher levels of inflammation (CRP) together formed a stress-related pathway tied to cardiovascular risk.
Editorial notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was provided by staff for clarity.
About this research summary
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original research: “Depression and Anxiety Associate with Adverse Cardiovascular Events via Neural, Autonomic and Inflammatory Pathways” by Shady Abohashem et al., published in Circulation: Cardiovascular Imaging. The study used Biobank data and advanced imaging and biomarker analyses to evaluate how neural stress responses and autonomic-immune mechanisms relate to major adverse cardiovascular events.
Abstract
Title: Depression and Anxiety Associate with Adverse Cardiovascular Events via Neural, Autonomic and Inflammatory Pathways
Background
Depression and anxiety often co-occur and share neurobiological mechanisms. Prior research has linked depression to major adverse cardiac events (MACE), but the contribution of stress-related neural activity and associated autonomic-immune pathways to that risk has been unclear. The authors hypothesized that increased stress-related neural activity and autonomic-immune dysregulation would partially mediate the relationship between mood disorders and MACE.
Methods
Data came from participants enrolled in the Mass General Brigham Biobank (2010–2020). A subset underwent 18F-FDG PET/CT to quantify stress-related neural activity as the amygdala-to-prefrontal cortex activity ratio. Heart rate variability and CRP served as measures of autonomic function and systemic inflammation. Depression and anxiety diagnoses were recorded at enrollment, and MACE were identified during follow-up. Statistical models controlled for demographics, lifestyle, cardiovascular risk factors, and socioeconomic variables.
Results
Among 85,551 participants, 3,078 (3.6%) developed MACE over a median follow-up of 3.4 years. Depression was associated with a higher risk of MACE (hazard ratio 1.24), with stronger associations for concurrent anxiety plus depression (hazard ratio 1.35); these relationships persisted after adjustment for confounders. In subgroups with imaging or biomarker data, depression correlated with higher amygdala-to-cortex activity, lower heart rate variability, and higher CRP. Mediation analyses indicated that these neural, autonomic, and inflammatory markers partially explained the association between emotional distress and MACE.
Conclusions
Depression and anxiety each associate with increased risk of major cardiovascular events, and risk is highest when both conditions are present. Part of this relationship appears to be mediated by heightened stress-related neural activity and autonomic-immune dysregulation, highlighting shared pathophysiology and potential targets for prevention and intervention.