Stress Signals Drive Cardiovascular Disease Risk in Patients With Depression, Anxiety

Depression and anxiety are independently associated with an increased risk of major adverse cardiovascular events (MACE) and are partially mediated by heightened stress-related neural activity, highlighting shared stress-related pathophysiology and exposing new potential avenues for treatment and prevention. The study findings were published by investigators in Circulation: Cardiovascular Imaging and discussed in a news release by Mass General Brigham, which led the study.^1,2

Which Factors Can Influence Cardiovascular Risk in Patients With Depression and Anxiety?

In the study, patients with depression had a correspondingly higher risk of MACE (hazard ratio [HR], 1.24; 95% CI, 1.14–1.34; P < .001), remaining statistically significant following adjustments for confounders. A stronger association was observed for concurrent anxiety plus depression (HR, 1.35; 95% CI, 1.23–1.49; P < .001).¹

Subsamples with available imaging or biomarkers were analyzed to determine specific factors that could influence risk. According to the authors, depression was linked to higher amygdala-to-cortex activity ratio (β = 0.16; P = .006), lower heart rate variability (β = –0.20; P < .001), and higher C-reactive protein (CRP) (β = 0.14; P < .001). Indirect effects due to these factors were observed on the depression-MACE relationship, with similar associations observed for anxiety or concurrent anxiety plus depression.¹

A total of 85,551 study subjects were included in the analysis, of which 3078 (3.6%) developed MACE over a median of 3.4 years of follow-up. Investigators utilized data from participants in the Mass General Brigham Biobank between 2010 and 2020.¹

“These findings give us a clearer biological picture of how emotional distress ‘gets under the skin’ and affects cardiovascular health,” Shady Abohashem, MD, MPH, study investigator and head of Cardiac/PET/CT Imaging Trials and MGH Cardiovascular Imaging Research Center of Massachusetts General Hospital, said in the news release.²

“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,” Abohashem continued.²

How Pharmacists Can Counsel Patients

The chosen biomarkers were selected due to their association with specific outcomes that link emotional stress and cardiovascular risk. The amygdala is a brain region associated with stress, while reduced heart rate variability can indicate an overactive nervous system, and high blood levels of CRP are linked to inflammation. The research demonstrates that patients with depression and anxiety experience specific pathophysiological changes that can influence their risk of MACE and necessitate a reevaluation of optimal treatment and prevention strategies in this population.²

“Together, these changes seem to form a biological chain linking emotional stress to cardiovascular risk,” Abohashem explained. “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.”²

Despite the promising results, the authors cautioned that the data was observational in nature, necessitating further research to more concretely determine if depression and anxiety can truly cause cardiovascular disease or whether there is a simple association. The data also present opportunities to better care for patients with depression, anxiety, or both, especially in mediating their cardiovascular risk. The current investigators are continuing their research in this regard, investigating whether interventions like stress-reduction therapies, lifestyle modifications, or anti-inflammatory medications could normalize the key immune and brain markers involved in cardiovascular risk.²

Pharmacists can play an essential role in counseling patients with mental health conditions on best practices for both primary treatment and secondary cardiovascular prevention. It is crucial that pharmacists provide ample support for patients with anxiety or depression and provide them the latest guidance from trustworthy advocacy groups on diet, lifestyle recommendations, and medication use for cardiovascular prevention. For patients with depression and anxiety, ensuring balance between treatments for their condition and consideration of their cardiovascular risk will be essential to the optimal management of both.¹

REFERENCES

1. Abohashem S, Qamar I, Grewal SS, et al. Depression and anxiety associate with adverse cardiovascular events via neural, autonomic, and inflammatory pathways. Circulation: Card Imag. Published Online December 17, 2025. doi:10.1161/CIRCIMAGING.124.017706

2. Mass General Brigham. Stress-related brain signals drive risk of cardiovascular disease in people with depression and anxiety. News Release. EurekAlert! Released December 17, 2025. Accessed December 22, 2025. https://www.eurekalert.org/news-releases/1109986