From Mind to Heart: Depression and Anxiety Increase Cardiovascular Risk
- Lidi Garcia
- Jan 15
- 4 min read
People with depression and anxiety have a higher risk of serious cardiac events. Part of this risk can be explained by changes in the brain related to stress, chronic inflammation, and dysregulation of the nervous system.
Depression and anxiety are primarily known for their effects on mental health, but increasingly, studies show that they also profoundly affect the body, especially the heart. People with depression have a higher risk of suffering serious cardiovascular events, such as heart attack, stroke, or death from cardiac causes. These events are called major adverse cardiac events in medicine.
What was not yet fully clear is how depression and anxiety "communicate" with the heart. One of the main suspects is chronic stress, which continuously activates specific brain circuits and triggers physical responses that, over time, can harm the cardiovascular system.
In the brain, a region called the amygdala functions as an emotional alarm. It detects threats, danger, and stressful situations, preparing the body to react. When the amygdala is overactive for extended periods, as happens in people with depression and anxiety, the body remains in a constant state of alert.
The prefrontal cortex, on the other hand, helps regulate these emotional responses, "braking" excess stress. An imbalance between these two regions may indicate a brain stuck in threat mode.
Researchers hypothesized that people with depression and/or anxiety exhibit increased brain activity related to stress, especially in the amygdala, and that this could explain, at least in part, the higher risk of heart problems. Furthermore, this brain stress could affect:
The autonomic nervous system, which controls automatic functions such as heartbeats;
The immune system, increasing inflammation in the body.
To investigate this, scientists analyzed data from over 85,000 participants in a large hospital biobank in the United States, followed over several years. At the beginning of the study, it was recorded whether each person had a diagnosis of depression, anxiety, both, or neither.
Some participants underwent advanced brain imaging scans (PET-CT), which allow for the measurement of the brain's metabolic activity. With these scans, the researchers calculated a ratio between amygdala activity and prefrontal cortex activity, an indirect indicator of stress-related neural activity.
Furthermore, they analyzed two important markers in the body: heart rate variability, which reflects the balance of the autonomic nervous system. Low values indicate that the body has difficulty adapting to stress; and C-reactive protein (CRP), a marker of inflammation in the blood. Elevated values indicate systemic inflammation, a known cardiovascular risk factor.
During the follow-up period, the researchers observed who developed serious cardiovascular events.
The results showed that people with depression had a significantly higher risk of suffering serious cardiac events, even after taking into account age, sex, lifestyle, previous medical conditions, and socioeconomic factors. This risk was even higher in people who had both depression and anxiety, suggesting a combined effect.
When they looked more closely at the biological mechanisms, the researchers found a clear pattern:
People with depression showed greater amygdala activity relative to the prefrontal cortex, indicating a brain more reactive to stress;
They showed lower heart rate variability, a sign of a less flexible nervous system;
They had higher levels of inflammation, as measured by CRP.
More advanced statistical analyses have shown that these factors, stress-related brain activity, autonomic nervous system dysregulation, and inflammation, explain part of the link between depression and heart problems.
In other words, depression doesn't just affect the "emotional state," but activates brain circuits and bodily responses that, over time, increase cardiovascular risk.
The same pattern was observed in people with isolated anxiety and, even more intensely, in those with both anxiety and depression.
This study shows that depression and anxiety are not just psychological conditions, but diseases involving the brain, nervous system, and immune system.
Chronic stress alters brain activity, increases inflammation, and impairs heart rate control, creating a biological environment conducive to the development of cardiovascular diseases. When depression and anxiety coexist, these effects seem to add up, further increasing the risk.
READ MORE:
Depression and Anxiety Associate With Adverse Cardiovascular Events via Neural, Autonomic, and Inflammatory Pathways
Shady Abohashem, Iqra Qamar, Simran S. Grewal, Giovanni Civieri,
Sabeeh Islam, Wesam Aldosoky, Sandeep Bollepalli, Rachel P. Rosovsky, Antonia V. Seligowski, Lisa M. Shin, Antonis A. Armoundas, Michael T. Osborne, and Ahmed Tawakol
Circulation, 17 December 2025
Abstract|:
Depression is linked to major adverse cardiac events (MACE), yet the role of stress-related neural activity–previously implicated in stress and anxiety—in mediating this association remains unclear. Because anxiety and depression frequently co-occur and share neurobiological pathways, we hypothesized 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. Data were obtained from participants enrolled in the Mass General Brigham Biobank (2010–2020). A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging to assess stress-related neural activity, defined as the ratio of amygdala to 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 concurrent anxiety plus depression) was modeled separately against study outcomes using linear and Cox regressions. Of 85 551 study subjects, 3078 (3.6%) participants developed MACE, over a median 3.4 years follow-up (interquartile range, 1.9–4.8). Depression was associated with higher MACE risk (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 demographics, lifestyle, cardiovascular, and socioeconomic factors. In subsamples with available imaging (N=1123) or biomarkers (heart rate variability, N=7862; CRP, N=12 906), depression was linked to higher amygdala-to-cortex activity ratio (β=0.16; P=0.006), lower heart rate variability (β=−0.20; P<0.001), and higher CRP (β=0.14; P<0.001). Mediation analyses 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 concurrent anxiety plus depression. Depression and anxiety independently associate with increased MACE risk, partly mediated by heightened stress-related neural activity and autonomic-immune dysregulation. The risk is greatest among those with both conditions, underscoring shared stress-related pathophysiology.
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