JAMA: Depression and Anxiety Associated with Cardiovascular Disease

A new study published in the Journal of American Medical Association showed that Reducing stress, blood pressure, and cholesterol may be beneficial for patients with depression or anxiety who wish to lessen their risk of myocardial infarction or stroke.

Major adverse cardiac events (MACE) are associated with depression, but it is unclear how stress-related brain activity which has previously been linked to stress and anxiety, mediates this association. Therefore, this study evaluated that elevated stress-related brain activity and associated autonomic-immune systems partially mediate the link between depression, anxiety, and their co-occurrence with MACE because anxiety and depression regularly co-occur and share neurobiological pathways.

Participants in the Mass General Brigham Biobank (2010–2020) provided the data. In order to measure the ratio of amygdala to background prefrontal cortex activity, a subgroup received 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. CRP (C-reactive protein) and heart rate variability were used as markers of systemic inflammation and autonomic activity. MACE was diagnosed using International Classification of Diseases codes during follow-up, and anxiety and depression were assessed during enrollment. Linear and Cox regressions were used to model each exposure (depression, anxiety, or concurrent anxiety plus depression) independently against study outcomes.

3078 (3.6%) of the 85,551 study participants experienced MACE during a median follow-up of 3.4 years (interquartile range, 1.9–4.8). Higher MACE risk was linked to depression (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).

These associations persisted even after controlling for socioeconomic, lifestyle, cardiovascular, and demographics. Depression was associated with 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) in subsamples with accessible imaging (N=1123) or biomarkers (heart rate variability, N=7862; CRP, N=12,906).

Heart rate variability, CRP, and the amygdala-to-cortex activity ratio all had indirect impacts on the depression–MACE association, according to mediation studies (log odds ratios, 0.04, 0.04, and 0.02, respectively; all P<0.05). Anxiety or concurrent anxiety and depression showed similar correlations.

Overall, anxiety and depression are separately linked to an increased risk of MACE, which is partially mediated by autonomic-immune dysregulation and increased stress-related brain activity. People who have both illnesses are at the highest risk, highlighting a common pathophysiology connected to stress.

Source:

Rubin, R. (2026). Stress may link depression and anxiety to cardiovascular disease. The Journal of the American Medical Association. https://doi.org/10.1001/jama.2025.25865