In 248 heart failure patients, those with depression had significantly worse cardiac remodeling, lower ejection fraction, and higher levels of BNP and angiotensin II compared to non-depressed patients.
BNP 66% higher in depressed patientsHeart failure patients with depression had BNP levels of 1,256 vs 756 pg/mL and angiotensin II of 86.4 vs 62.5 ng/mL, suggesting depression amplifies the peptide pathways driving cardiac damage
What the researchers found
Heart failure patients with depression (Hamilton Depression Scale score ≥17) showed significantly worse cardiac parameters compared to non-depressed patients:
- Left ventricular ejection fraction: 42.3% ± 6.7% vs 51.6% ± 5.9% (depressed vs non-depressed)
- B-type natriuretic peptide: 1,256 ± 345 pg/mL vs 756 ± 234 pg/mL — a 66% higher level in depressed patients
- Angiotensin II: 86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL — a 38% higher level
- TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL
- IL-6 was also significantly elevated in the depressed cohort
These findings suggest depression accelerates cardiac remodeling and left ventricular dysfunction through inflammatory cascades and neuroendocrine overactivation.
Why it matters
Depression affects up to 40% of heart failure patients and is associated with worse outcomes, but the mechanisms have been unclear. This study provides specific biomarker evidence linking depression to higher levels of BNP and angiotensin II — two peptides central to heart failure pathophysiology. This suggests that treating depression in heart failure patients could reduce harmful neuroendocrine activation and slow disease progression, not just improve quality of life.
How the study worked
This was a retrospective study of 248 chronic heart failure patients treated at a tertiary care center between January 2018 and December 2022. Patients were classified as depressed or non-depressed using the Hamilton Depression Scale (cutoff score of 17). Cardiac morphology and function were assessed by echocardiography and cardiac MRI. Blood biomarkers included B-type natriuretic peptide, angiotensin II, TNF-α, and IL-6.
What this study cannot tell us
This is a retrospective observational study, so it cannot prove that depression causes worse cardiac function — the relationship may be bidirectional or confounded by disease severity. The Hamilton Depression Scale is a validated but subjective measure. Medication use (antidepressants, ACE inhibitors, beta-blockers) was not controlled for in the abstract. The abstract text appears to have some formatting or translation issues that may obscure some numerical comparisons.
How to read the evidence
This is a retrospective observational study with a reasonable sample size (248 patients) and clear biomarker data. However, the retrospective design, potential confounders, and inability to establish causation limit the evidence strength.
When this study was published
Published in 2025, this study reflects current clinical interest in the bidirectional relationship between mental health and cardiovascular disease, with a focus on measurable peptide biomarkers.
The bigger picture
This study connects psychiatry with cardiovascular peptide biology. The renin-angiotensin-aldosterone system (RAAS) — through angiotensin II — and the natriuretic peptide system (BNP) are the two most important peptide pathways in heart failure. Finding that depression significantly amplifies both pathways provides a mechanistic rationale for integrated cardiac-psychiatric care and suggests that RAAS-blocking drugs (ACE inhibitors, ARBs) may be especially important in depressed heart failure patients.
Questions still open
- Would treating depression with antidepressants or psychotherapy reduce BNP and angiotensin II levels and slow cardiac remodeling?
- Are RAAS inhibitors (ACE inhibitors, ARBs) more beneficial in depressed heart failure patients than non-depressed patients?
- Could BNP and angiotensin II levels serve as biomarkers to monitor the cardiac impact of depression treatment in heart failure?
Common questions
How does depression make heart failure worse?
Should heart failure patients be screened for depression?
Read the original research
Depressive state on cardiac remodeling and left ventricular function in chronic heart failure: A retrospective study.
World journal of psychiatry, 15(9), 106906
Citation
Gao, Bo; Gao, Yun-Fan; Chu, Meng-Ting; Yuan, Ke-Fang. (2025). Depressive state on cardiac remodeling and left ventricular function in chronic heart failure: A retrospective study.. World journal of psychiatry, 15(9), 106906. https://doi.org/10.5498/wjp.v15.i9.106906