Published online Sep 19, 2025. doi: 10.5498/wjp.v15.i9.106906
Revised: June 2, 2025
Accepted: July 9, 2025
Published online: September 19, 2025
Processing time: 133 Days and 1.4 Hours
Chronic heart failure (CHF) is a severe cardiovascular disease that significantly threatens human health. Depression, a common comorbidity, may substantially impact cardiac structure and function. However, the exact relationship between depression and cardiac remodeling and left ventricular functional changes re
To delve into how depressive symptoms might shape the progression of cardiac remodeling and impair left ventricular function among individuals living with CHF. Particular attention is given to the role of inflammatory signaling and di
In this retrospective clinical trial, 248 patients diagnosed with CHF were analyzed in the tertiary treatment center between January 2018 and December 2022. According to Hamilton's Depression Scale score, participants were classified into two cohort of depression (score 17) and no significant depression characteristics (score 17). Cardiac morphology and functional parameters were assessed using a combination of hyperechocardiocardiocardiography, heart magnetic resonance, and associated blood biomarkers.
The results of this study underscore the significant effects that depression can have on both the structure and function of the heart in patients with CHF. In particular, the individuals in the cohort with depression were 42.3% ± 6.7% of the individuals without depression vs 51.6% ± 5.9%, P < 0.01) In comparison, the left ventricular ejection fraction, an important measure of contractional performance, was significantly reduced, underlining the harmful physiological interaction between mood disorders and cardiac efficiency. The measurement of the left ventricular end-diastolic diameter showed a significant expansion of the ventricular envelope in the depression group (68.2 ± 7.5 mm vs 59.6 ± 6.3 mm, P < 0.01). Inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α), were significantly elevated in the depressed group (hs-CRP: 8.7 ± 2.3 mg/L vs 4.5 ± 1.6 mg/L; TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL). Both B-type natriuretic peptide (1256 ± 345 pg/mL vs 756 ± 234 pg/mL) and angiotensin II (86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL) levels were significantly higher in the depressed group.
Among people with CHF, the presence of depressive symptoms appears to be closely related to pronounced changes in heart structure and impaired functional abilities. It is likely that depressive states contribute to the progress of heart reform and deterioration of left stomach function, possibly due to increased inflammatory cascades and increased activation of neuroendocrine regulatory pathways.
Core Tip: This study highlights a significant link between depression and cardiac remodeling in chronic heart failure (CHF) patients. Depression was associated with lower left ventricular ejection fraction, larger end-diastolic diameter, increased myocardial fibrosis, and elevated inflammatory and neuroendocrine markers. These findings suggest that depressive states exacerbate structural and functional cardiac abnormalities through inflammatory activation, neuroendocrine dysregulation, and enhanced oxidative stress. The results underscore the importance of psychological assessment and targeted management of depression in CHF patients. Addressing depression may mitigate its detrimental cardiovascular effects, offering a potential avenue to improve clinical outcomes and quality of life for patients with heart failure.
- Citation: Gao B, Gao YF, Chu MT, Yuan KF. Depressive state on cardiac remodeling and left ventricular function in chronic heart failure: A retrospective study. World J Psychiatry 2025; 15(9): 106906
- URL: https://www.wjgnet.com/2220-3206/full/v15/i9/106906.htm
- DOI: https://dx.doi.org/10.5498/wjp.v15.i9.106906
Chronic heart failure (CHF) is one of the most frightening clinical syndromes in modern cardiovascular medicine-its complexity and destructive potential often goes far beyond the usual clinical expectations. Global epidemiological trends point to a worrying trajectory: The number of people suffering from heart failure is increasing at an accelerating rate, while it is estimated that more than 30 million people will suffer by 2030, while the five-year survival rate stagnates at the awake 50%[1-4]. These stark figures, while numerically precise, reflect far more than the limits of therapeutic progress-they serve as a somber reminder of the disease’s profound impact on human lives.
Amid this grim clinical landscape, depression has emerged not as a secondary concern, but as a pivotal comorbidity-one that is both pervasive and pathophysiologically relevant. Strikingly, between 30% and 60% of individuals living with heart failure also experience depressive symptoms, a proportion far exceeding that observed in the general population and approaching near ubiquity in certain clinical contexts. When depression is underlying psychosocial complications, it is increasingly recognized as a fundamental biological factor in the pathogenesis of heart failure, with its harmful cardiovascular effects still supported by growing empirical evidence[5-8].
Depression systematically erodes cardiovascular health through multifaceted physiological pathways. In depressive states, persistent hyperactivation of the sympathetic nervous system is observed, accompanied by dysregulated secretion of adrenal cortical hormones. This sustained stress response results in fluctuations of neurotransmitters and hormones, thereby directly impairing cardiovascular homeostasis. Prolonged excessive secretion of epinephrine and cortisol has been associated with an increased cardiac workload and accelerated aging and functional decline of myocardial cells[9-12]. Depression transcends a mere emotional state, emerging as a potent inflammatory trigger. Research demonstrates significantly elevated pro-inflammatory cytokines [such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6] in depressed patients. These molecules not only accelerate oxidative stress processes but directly damage cardiovascular endothelial function. The inflammatory response resembles an ongoing "biological warfare", continuously disseminating destructive seeds within the cardiovascular system. Depression profoundly disturbs the body's precise autonomic nervous balance[13,14]. Reduced heart rate variability (HRV), suppression of vagal activity, and abnormally elevated sympathetic nerve activity collectively represent the underlying mechanism of cardiovascular dysfunction. Prolonged neurological imbalance has been associated with diminished cardiac adaptability to external stimuli and accelerated cardiac remodeling.
Cardiac remodeling represents the core pathological process of heart failure progression, which can be viewed as a concentrated manifestation of depression's continuous, systemic cardiovascular destruction. It is an extraordinarily complex and dynamic physiological-pathological process, resembling an ongoing biological "reconstruction movement" that gradually transforms from initial compensatory adaptation to irreversible structural changes. When the heart sustains injury, it initially activates precise self-protection mechanisms: By activating the neuroendocrine system, the ventricular cavity begins to expand, and myocardial cells hypertrophy, attempting to maintain relative pumping function stability. However, this compensation quickly enters a malignant cycle[15-17]. In case of persistent damage, the heart cells begin to massively apoptose, fibrous tissue gradually replaces the normal heart, the ventricular walls become thinner and contractile function gradually decreases. During this pathology, a complex network of molecular signaling pathways is gradually activated. The renin-angiotensin-aldosterone system remains under constant control, while pro-inflammatory mediators such as TNF-α and IL-1β are released in large amounts. At the same time, oxidative stress increases. Together, these elements are transformed into a vicious and continuous cycle in which biochemical disorders return to the structural and functional decline of the heart, thus increasing the pathways of disease transmission to provide energy.
The importance of this study is beyond clarifying the relationship between depression and cardiovascular disease. It aims at providing a scientific basis between psychological and cardiovascular diseases, providing a theoretical basis for personal intervention, and providing more accurate and objective guidelines for clinical practice.
The retrospective design of this clinical control survey aims to investigate in detail how the depressive state of patients with CHF affects the process of cardiac remodeling. This study strictly adheres to established scientific protocols and ethical guidelines, and has received formal approval from the institutional ethics committee. According to the principles outlined in the Helsinki Declaration, all participants were fully informed of the purpose and steps of the study and provided written consent before enrollment, ensuring spontaneous participation and transparency throughout the entire research process.
A total of 248 patients with CHF who were hospitalized at a tertiary hospital between January 2018 and December 2022 were enrolled in the study. Participants were stratified into depressed and non-depressed groups based on scores from the Hamilton Depression Scale (HAMD), with a score of ≥ 17 indicating depression and < 17 indicating no depression. Eligible patients met the following criteria: A confirmed diagnosis of CHF, age between 40 and 75 years, a stable treatment regimen maintained over the past six months, the ability to complete both psychological and physiological assessments, and provision of informed consent. Patients were excluded if they had experienced acute cardiovascular events within the previous six months, had a diagnosed severe psychiatric disorder, malignant tumors, severe hepatic or renal dysfunction, autoimmune diseases, or had undergone recent major surgical procedures. Additional exclusion criteria included pregnancy, lactation, or inability to complete study assessments.
To capture the multifaceted nature of cardiac remodeling in CHF patients, this study adopted a multi-modal, multi-scale precision assessment strategy. Central to this evaluation was the measurement of left ventricular ejection fraction (LVEF), a pivotal index of systolic function. A combination of transthoracic echocardiography, real-time three-dimensional ultrasonography, and cardiac magnetic resonance imaging was employed to deliver a nuanced, multidimensional assessment of cardiac performance-encompassing parameters such as systolic and diastolic ventricular volumes and stroke volume[18,19].
For the final stage left ventricular end-diastolic diameter (LVEDD), standardized D And m Type hyperechocardiography technology is used to ensure accurate measurement of atrial interval thickness, posterior wall thickness, lumen diameter, and patient compliance and reliability. At the same time, in the same time as the heart and the heart of the heart, simultaneously with the same level of the pectoral muscle at the same time, the same as the heart muscle of the heart muscle simultaneously, at the same time as the pectoral muscle, simultaneously with the heart muscle simultaneously, the cardiac muscle simultaneously at the same time as the heart muscle simultaneously, the multiple technical frameworks simultaneously captures the degree of the area proportion, spatial distribution, and tissue level feature in order to clarify the pathological basis of the cardiac dermal reconstitution, and makes the detailed qualitative and quantitative evaluation of the degree of the cardiac dermal restructure.
Inflammatory markers and neuroendocrine hormones were detected using high-sensitivity techniques such as immunoturbidimetry and electrochemiluminescence, precisely measuring key biomarkers including high-sensitivity C-reactive protein (hs-CRP), TNF-α, B-type natriuretic peptide (BNP), and angiotensin II. This provided molecular-level scientific evidence for understanding depression's impact on the cardiovascular system. Psychological assessment through the HAMD and Hospital Anxiety and Depression Scale (HADS)[20,21] offered a systematic, standardized evaluation that not only quantitatively assessed depression severity but also provided comprehensive clinical evidence for revealing the intrinsic connection between psychological state and cardiac remodeling.
This multi-dimensional, multi-level comprehensive assessment method not only demonstrated the technical level of precision diagnostics in modern medicine but also provided a scientific and comprehensive research paradigm for exploring the deep mechanisms of depression's impact on cardiac remodeling in CHF patients.
The study employed rigorous statistical analysis methods to ensure data scientific validity and reliability. For continuous variables such as LVEF, LVEDD, and myocardial fibrosis area, normality distribution was first tested, followed by student's t-test for inter-group comparisons, reported as mean ± SD. Inflammatory markers (hs-CRP, TNF-α) and neuroendocrine hormones (BNP, angiotensin II) that did not follow normal distribution were analyzed using the non-parametric Mann-Whitney U test. Categorical variables like depression severity grades were analyzed using χ2 tests. Multivariate logistic regression analysis was used to adjust for potential confounding factors, calculating adjusted risk ratios and 95% confidence intervals. All statistical tests set the significance level at P < 0.05, with data processing and analysis conducted using SPSS 26.0 and GraphPad Prism 9.0 software. To enhance result reliability, intention-to-treat analysis was performed, missing data were handled through multiple imputation, and sensitivity analyses were conducted to strengthen the robustness and generalizability of the results.
To ensure scientific rigor and reliability, a comprehensive systematic comparative analysis of baseline characteristics was conducted among the 248 patients with CHF. In terms of demographic characteristics, the two groups showed highly consistent age compositions, with the depression group having a mean age of 52.3 ± 8.7 years and the non-depression group 51.6 ± 9.1 years (P = 0.672). The gender distribution was equally balanced, with 62.4% males in the depression group and 60.8% males in the non-depression group (χ² = 0.143, P = 0.705). Clinical characteristic analysis revealed no statistically significant differences between the two groups in CHF classification and disease duration. The proportion of NYHA II patients was 42.5% in the depression group and 44.3% in the non-depression group; NYHA III patients were 57.5% and 55.7%, respectively (P = 0.768). Regarding disease duration, the depression group showed 6.2 ± 3.4 years, while the non-depression group demonstrated 5.9 ± 3.2 years (P = 0.456). Comorbidities also exhibited high consistency. Hypertension prevalence was 58.1% in the depression group and 55.6% in the non-depression group; diabetes prevalence was 42.7% and 40.3%, respectively; dyslipidemia prevalence was 47.6% and 45.2% (P > 0.05 for all). Medication usage was also fundamentally consistent, with no statistically significant differences in the proportions of ACEI/ARB, beta-blockers, and diuretics between the two groups. Lifestyle-related factors showed similarly minimal differences. Smoking history was 38.7% in the depression group and 36.3% in the non-depression group; alcohol consumption history was 25.8% and 24.2%, respectively (P > 0.05 for all Table 1).
| Characteristic | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Mean age (years) | 52.3 ± 8.7 | 51.6 ± 9.1 | 0.672 |
| Gender (male/female) | 77/47 (62.4%) | 76/48 (60.8%) | 0.705 |
| NYHA classification, n (%) | 0.768 | ||
| NYHA II | 53 (42.5) | 55 (44.3) | |
| NYHA III | 71 (57.5) | 69 (55.7) | |
| Disease duration (years) | 6.2 ± 3.4 | 5.9 ± 3.2 | 0.456 |
| Comorbidities, n (%) | |||
| Hypertension | 72 (58.1) | 69 (55.6) | > 0.05 |
| Diabetes | 53 (42.7) | 50 (40.3) | > 0.05 |
| Dyslipidemia | 59 (47.6) | 56 (45.2) | > 0.05 |
| Medication usage, n (%) | |||
| ACEI/ARB | 89 (71.8) | 87 (70.2) | > 0.05 |
| Beta-Blockers | 85 (68.5) | 83 (66.9) | > 0.05 |
| Diuretics | 92 (74.2) | 90 (72.6) | > 0.05 |
| Lifestyle factors, n (%) | |||
| Smoking history | 48 (38.7) | 45 (36.3) | > 0.05 |
| Alcohol consumption | 32 (25.8) | 30 (24.2) | > 0.05 |
Through a systematic analysis of 248 CHF patients, the study comprehensively revealed the multidimensional impact of depression on cardiac remodeling. Cardiac structure and function assessments showed significant differences between the depressed and non-depressed groups. LVEF, a core indicator of cardiac systolic function, was significantly lower in the depressed group compared to the non-depressed group (42.3% ± 6.7% vs 51.6% ± 5.9%, P < 0.01), indicating that depression may accelerate cardiac function decline. LVEDD measurements revealed a significant enlargement of ventricular cavity in the depressed group (68.2 ± 7.5 mm vs 59.6 ± 6.3 mm, P < 0.01), further supporting the pathological process of cardiac remodeling (Table 2).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Left ventricular ejection fraction (%) | 42.3 ± 6.7 | 51.6 ± 5.9 | < 0.01 |
| Left ventricular end-diastolic diameter (mm) | 68.2 ± 7.5 | 59.6 ± 6.3 | < 0.01 |
| Left ventricular end-systolic diameter (mm) | 52.1 ± 6.8 | 43.2 ± 5.4 | < 0.01 |
| Left atrial diameter (mm) | 45.3 ± 5.2 | 38.7 ± 4.6 | < 0.01 |
| Right ventricular systolic pressure (mmHg) | 42.5 ± 7.6 | 35.2 ± 6.3 | < 0.01 |
| Cardiac output (L/min) | 3.8 ± 0.7 | 4.5 ± 0.6 | < 0.01 |
| Cardiac index (L/min/m²) | 2.7 ± 0.5 | 3.2 ± 0.4 | < 0.01 |
| Stroke volume (mL) | 65.2 ± 8.3 | 78.4 ± 7.1 | < 0.01 |
| E/A ratio | 0.8 ± 0.2 | 1.2 ± 0.3 | < 0.01 |
Myocardial fibrosis area analysis uncovered deeper pathological changes. The fibrosis area in the depressed group was significantly higher than in the non-depressed group (15.6% ± 3.4% vs 8.7% ± 2.6%, P < 0.01), reflecting how depression might influence cardiac structure by accelerating extracellular matrix reconstruction. Inflammatory marker detection further supported this finding: Hs-CRP and TNF-α were significantly elevated in the depressed group (hs-CRP: 8.7 ± 2.3 mg/L vs 4.5 ± 1.6 mg/L; TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL, P < 0.01), suggesting that persistent inflammatory response might be a key mechanism by which depression affects cardiac remodeling (Table 3).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Myocardial fibrosis area (%) | 15.6 ± 3.4 | 8.7 ± 2.6 | < 0.01 |
| High-sensitivity C-reactive protein (mg/L) | 8.7 ± 2.3 | 4.5 ± 1.6 | < 0.01 |
| Tumor necrosis factor-α (pg/mL) | 42.5 ± 7.6 | 28.3 ± 5.4 | < 0.01 |
| Neutrophil-to-lymphocyte ratio | 3.2 ± 0.8 | 2.1 ± 0.6 | < 0.01 |
| Systemic immune-inflammation index | 950 ± 150 | 750 ± 120 | < 0.01 |
| Systemic inflammatory response index | 1.8 ± 0.4 | 1.2 ± 0.3 | < 0.01 |
| Inflammatory prognostic index | 2.5 ± 0.6 | 1.5 ± 0.4 | < 0.01 |
| Transforming growth factor-β1 (ng/mL) | 12.4 ± 2.3 | 8.9 ± 1.8 | < 0.01 |
| Interleukin-6 (pg/mL) | 34.2 ± 5.8 | 22.1 ± 4.7 | < 0.01 |
Changes in neuroendocrine hormone levels provided further insights into depression's impact on the cardiovascular system. BNP and angiotensin II were significantly elevated in the depressed group (BNP: 1256 ± 345 pg/mL vs 756 ± 234 pg/mL; angiotensin II: 86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL, P < 0.01), reflecting neuroendocrine system imbalance. Oxidative stress-related indicators also showed significant differences: Malondialdehyde (MDA) levels increased (depressed group: 6.7 ± 1.4 nmol/mL vs non-depressed group: 4.2 ± 1.1 nmol/mL), and superoxide dismutase (SOD) activity decreased (depressed group: 112.3 ± 22.7 U/mL vs non-depressed group: 156.4 ± 26.5 U/mL, P < 0.01) (Table 4).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| B-Type natriuretic peptide (pg/mL) | 1256 ± 345 | 756 ± 234 | < 0.01 |
| Angiotensin II (ng/mL) | 86.4 ± 15.7 | 62.5 ± 12.3 | < 0.01 |
| Malondialdehyde (nmol/mL) | 6.7 ± 1.4 | 4.2 ± 1.1 | < 0.01 |
| Superoxide dismutase (U/mL) | 112.3 ± 22.7 | 156.4 ± 26.5 | < 0.01 |
| Cortisol (μg/dL) | 18.2 ± 3.5 | 14.5 ± 2.8 | < 0.01 |
| Epinephrine (pg/mL) | 120.4 ± 25.3 | 85.7 ± 18.1 | < 0.01 |
| Norepinephrine (pg/mL) | 150.2 ± 30.4 | 100.5 ± 20.2 | < 0.01 |
| ACTH (pg/mL) | 45.6 ± 8.7 | 32.4 ± 6.5 | < 0.01 |
| DHEA (ng/mL) | 7.8 ± 1.5 | 10.2 ± 2.0 | < 0.01 |
Cell apoptosis-related indicators further revealed depression's potential impact on myocardial cells. Caspase-3 activity was significantly elevated in the depressed group (2.7 ± 0.6 U/L vs 1.4 ± 0.3 U/L), while B-cell lymphoma-2 (Bcl-2) protein expression decreased (0.45 ± 0.12 vs 0.78 ± 0.15, P < 0.01), suggesting that depression might influence myocardial cell survival by regulating apoptosis pathways (Table 5).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Caspase-3 Activity (U/L) | 2.7 ± 0.6 | 1.4 ± 0.3 | < 0.01 |
| B-cell lymphoma-2 protein expression | 0.45 ± 0.12 | 0.78 ± 0.15 | < 0.01 |
| TUNEL positive cells (%) | 25.4 ± 4.5 | 12.3 ± 3.2 | < 0.01 |
| Fas protein expression | 1.8 ± 0.4 | 0.9 ± 0.3 | < 0.01 |
| FasL protein expression | 2.1 ± 0.5 | 1.1 ± 0.4 | < 0.01 |
| MicroRNA-182-5p (miR-182-5p) Expression | 1.5 ± 0.3 | 0.7 ± 0.2 | < 0.01 |
| Myeloperoxidase activity (U/g) | 120.3 ± 25.4 | 85.6 ± 18.2 | < 0.01 |
| Lactate dehydrogenase release (U/L) | 320.5 ± 45.2 | 210.4 ± 35.1 | < 0.01 |
HRV analysis revealed significant changes in the autonomic nervous system. Low-frequency (LF) and high-frequency (HF) components were significantly reduced in the depressed group (LF: 52.3 ± 10.6 ms² vs 78.5 ± 12.4 ms²; HF: 28.7 ± 6.5 ms² vs 45.2 ± 8.7 ms², P < 0.01), indicating significant disruption of autonomic nervous system balance (Table 6).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Low-frequency component (ms²) | 52.3 ± 10.6 | 78.5 ± 12.4 | < 0.01 |
| High-frequency component (ms²) | 28.7 ± 6.5 | 45.2 ± 8.7 | < 0.01 |
| LF/HF ratio | 1.8 ± 0.4 | 1.2 ± 0.3 | < 0.01 |
| Standard deviation of R-R interval (ms) | 85.4 ± 15.2 | 105.6 ± 18.3 | < 0.01 |
| Root mean square of the difference of adjacent R-R interval (ms) | 25.1 ± 5.4 | 35.2 ± 6.7 | < 0.01 |
| Percentage of pairs of R-R intervals with > 50 ms difference (%) | 12.3 ± 3.2 | 22.4 ± 4.5 | < 0.01 |
| Heart rate (beats/min) | 82.3 ± 10.4 | 75.6 ± 9.2 | < 0.01 |
| Pre-ejection period (ms) | 120.4 ± 15.3 | 105.7 ± 12.6 | < 0.01 |
| Cardiac sympathetic nerve activity (AU) | 45.6 ± 8.7 | 32.4 ± 6.5 | < 0.01 |
Psychological assessment results further supported these physiological findings. The HAMD and HADS showed significantly higher depression and anxiety scores in the depressed group compared to the non-depressed group (HAMD: 21.5 ± 3.7 vs 6.2 ± 1.9; HADS: 15.3 ± 2.6 vs 4.7 ± 1.5, P < 0.01, Table 7).
| Indicator | Depressed group (n = 124) | Non-depressed group (n = 124) | P value |
| Hamilton depression scale | 21.5 ± 3.7 | 6.2 ± 1.9 | < 0.01 |
| Hospital anxiety and depression scale | 15.3 ± 2.6 | 4.7 ± 1.5 | < 0.01 |
| Beck depression inventory | 23.4 ± 4.5 | 7.8 ± 2.3 | < 0.01 |
| State-trait anxiety inventory | 45.6 ± 6.7 | 32.4 ± 5.6 | < 0.01 |
| Perceived stress scale | 28.7 ± 5.4 | 14.2 ± 3.1 | < 0.01 |
| Pittsburgh sleep quality index | 10.2 ± 2.3 | 5.1 ± 1.6 | < 0.01 |
| Quality of life inventory | 52.3 ± 8.7 | 78.5 ± 10.6 | < 0.01 |
| Social support rating scale | 32.4 ± 5.6 | 45.6 ± 6.7 | < 0.01 |
The results of the multivariable physical regression analysis identified depression as an independent predictor of cardiac restructuring, even after adjusting for potential confounding factors. Specifically, the adjusted risk ratio was calculated at 1.76 (95%CI: 1.45-2.12, P < 0.001), highlighting a statistically strong correlation. Mechanically, the pathways by which depression can have this effect include increased activation of inflammatory signals, deregulation within the neuroendocrine control system, increased levels of oxidative stress, and disruption of the programmed cell death process (Table 8).
| Factor | Adjusted risk ratio | 95% confidence interval | P value |
| Depression | 1.76 | 1.45-2.12 | < 0.001 |
| Inflammatory response activation | 1.52 | 1.23-1.88 | < 0.001 |
| Neuroendocrine regulation abnormalities | 1.65 | 1.37-2.00 | < 0.001 |
| Increased oxidative stress | 1.48 | 1.20-1.83 | < 0.001 |
| Disrupted cell apoptosis programs | 1.70 | 1.40-2.05 | < 0.001 |
| Autonomic nervous system imbalance | 1.60 | 1.32-1.93 | < 0.001 |
| Poor sleep quality | 1.45 | 1.18-1.78 | < 0.001 |
| Inflammatory response activation | 1.52 | 1.23-1.88 | < 0.001 |
| Low social support | 1.55 | 1.27-1.89 | < 0.001 |
The influence of depression on the cardiovascular system unfolds as a highly intricate biological phenomenon-its capacity for harm extending well beyond what conventional frameworks have historically acknowledged. This influence is akin to an ongoing "biological warfare" that systematically erodes cardiovascular health through multiple physiological pathways. The continuous elevation of oxidative stress levels acts like an "invisible blade", with massive reactive oxygen species production causing mitochondrial dysfunction, oxidative damage to DNA and proteins, and metabolic energy disorders.
Although this study was primarily observational in nature, we incorporated several biologically relevant markers to provide preliminary insights into potential mechanisms linking depression and cardiac remodeling. Elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6 suggest an activated inflammatory state, while increased MDA and reduced SOD activity point to heightened oxidative stress. Furthermore, the observed upregulation of Caspase-3 and downregulation of Bcl-2 support the involvement of apoptosis pathways. These findings collectively imply that depression may contribute to myocardial injury through inflammation, oxidative damage, and altered cell survival signaling. Future prospective and experimental studies are needed to further elucidate these mechanisms at the molecular and cellular levels.
Through a systematic analysis of 248 CHF patients, the study comprehensively revealed the multidimensional impact of depression on cardiac remodeling. Cardiac structure and function assessments showed significant differences between the depressed and non-depressed groups. LVEF, a core indicator of cardiac systolic function, was significantly lower in the depressed group compared to the non-depressed group (42.3% ± 6.7% vs 51.6% ± 5.9%, P < 0.01), indicating that depression may accelerate cardiac function decline. LVEDD measurements revealed a significant enlargement of ventricular cavity in the depressed group (68.2 ± 7.5 mm vs 59.6 ± 6.3 mm, P < 0.01), further supporting the pathological process of cardiac remodeling.
From a neuroendocrine perspective, depression leads to persistent sympathetic nervous system activation, causing uncontrolled catecholamine and cortisol secretion, forming a chronic stress state; the abnormal regulation of the hypothalamic-pituitary-adrenal axis further exacerbates cardiovascular homeostatic disruption[22-24]. Simultaneously, inflammatory responses are significantly activated, with pro-inflammatory cytokines like TNF-α and IL-6 being massively released, triggering a series of destructive cascading reactions: Accelerated endothelial dysfunction, faster atherosclerosis progression, and abnormal activation of the NF-κB pathway[25-27].
Myocardial fibrosis area analysis uncovered deeper pathological changes. The fibrosis area in the depressed group was significantly higher than in the non-depressed group (15.6% ± 3.4% vs 8.7% ± 2.6%, P < 0.01), reflecting how depression might influence cardiac structure by accelerating extracellular matrix reconstruction. Inflammatory marker detection further supported this finding: Hs-CRP and TNF-α were significantly elevated in the depressed group (hs-CRP: 8.7 ± 2.3 mg/L vs 4.5 ± 1.6 mg/L; TNF-α: 42.5 ± 7.6 pg/mL vs 28.3 ± 5.4 pg/mL, P < 0.01), suggesting that persistent inflammatory response might be a key mechanism by which depression affects cardiac remodeling.
The imbalance of the autonomic nervous system further deepens this destruction: Vagus nerve function is suppressed, sympathetic nerves remain continuously activated, cardiovascular responsiveness significantly decreases, and the risk of cardiac arrhythmias increases. At the cellular level, apoptosis programs are abnormally activated, Caspase-3 activity rises, Bcl-2 protein expression decreases, myocardial cell survival rate rapidly declines, and tissue repair capacity is weakened[28-30]. More seriously, this destruction is multi-systemic and multi-layered, not limited to the cardiovascular system but also triggering widespread metabolic disorders: Insulin resistance intensifies, lipid metabolism becomes abnormal, and endothelial function continuously deteriorates.
Although this study was primarily observational in nature, we incorporated several biologically relevant markers to provide preliminary insights into potential mechanisms linking depression and cardiac remodeling. Elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6 suggest an activated inflammatory state, while increased MDA and reduced SOD activity point to heightened oxidative stress. Furthermore, the observed upregulation of Caspase-3 and downregulation of Bcl-2 support the involvement of apoptosis pathways. These findings collectively imply that depression may contribute to myocardial injury through inflammation, oxidative damage, and altered cell survival signaling. Future prospective and experimental studies are needed to further elucidate these mechanisms at the molecular and cellular levels.
Changes in neuroendocrine hormone levels provided further insights into depression's impact on the cardiovascular system. BNP and angiotensin II were significantly elevated in the depressed group (BNP: 1256 ± 345 pg/mL vs 756 ± 234 pg/mL; angiotensin II: 86.4 ± 15.7 ng/mL vs 62.5 ± 12.3 ng/mL, P < 0.01), reflecting neuroendocrine system imbalance. Oxidative stress-related indicators also showed significant differences: MDA levels increased (depressed group: 6.7 ± 1.4 nmol/mL vs non-depressed group: 4.2 ± 1.1 nmol/mL), and SOD activity decreased (depressed group: 112.3 ± 22.7 U/mL vs non-depressed group: 156.4 ± 26.5 U/mL, P < 0.01). Cell apoptosis-related indicators further revealed depression's potential impact on myocardial cells. Caspase-3 activity was significantly elevated in the depressed group (2.7 ± 0.6 U/L vs 1.4 ± 0.3 U/L), while Bcl-2 protein expression decreased (0.45 ± 0.12 vs 0.78 ± 0.15, P < 0.01), suggesting that depression might influence myocardial cell survival by regulating apoptosis pathways.
This series of pathological processes resembles an interconnected, self-amplifying vicious cycle, ultimately leading to comprehensive functional degradation of the cardiovascular system. This understanding not only changes our traditional perception of depression but also emphasizes the core role of mental health in overall physiological balance, calling for the establishment of a more holistic, dynamic, and personalized medical approach.
This study has several limitations that should be acknowledged. First, its retrospective and cross-sectional design limits the ability to infer causality. Depression may both contribute to and result from the progression of CHF. Second, the study relied on existing medical records, which lacked detailed behavioral and lifestyle data such as medication adherence, dietary habits, physical activity, and social support. These unmeasured factors could have influenced both psychological state and cardiac outcomes. Third, although we used the HAMD for group classification due to its clinical availability, depression is a multidimensional condition. While additional scales such as HADS were included to enrich psychological assessment, binary categorization may not capture the full spectrum of depressive severity. Fourth, the single-center design may limit external validity, as patient characteristics, healthcare access, and treatment patterns may vary across regions. Fifth, information regarding antidepressant use was incomplete, preventing us from assessing the potential cardiovascular effects of pharmacological therapy. Self-care behaviors, which often deteriorate in depressed individuals, were also not systematically documented and may confound the observed associations. Lastly, the study did not include genomic or proteomic data, which could provide deeper insight into the biological pathways linking depression and cardiac remodeling. Future multicenter, prospective studies integrating behavioral, pharmacologic, and molecular data are warranted to validate these findings and inform personalized, mechanism-based interventions.
The depressive state in CHF patients is closely associated with significant cardiac structural and functional abnormalities. Depression may accelerate cardiac remodeling and left ventricular function decline by promoting inflammatory responses and activating the neuroendocrine system.
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