Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide despite advances in interventional and pharmacological therapies.¹ Beyond conventional risk factors—such as hypertension, diabetes, dyslipidemia, and smoking—psychological factors including depression and anxiety have emerged as potent yet under-recognized determinants of cardiovascular outcomes.² Depression is observed in approximately 20–40% of post-myocardial infarction (MI) patients, while anxiety disorders occur in up to 45%, frequently coexisting and compounding disease burden.³

Multiple biological mechanisms link affective disorders with adverse cardiac prognosis. Depression and anxiety contribute to autonomic imbalance, increased sympathetic tone, platelet hyperreactivity, endothelial dysfunction, and heightened inflammatory cytokine release, culminating in plaque instability and arrhythmogenic potential.⁴ Moreover, behavioral mechanisms such as poor medication adherence, reduced physical activity, smoking, and delayed treatment seeking further amplify cardiovascular risk.⁵ Studies such as the ENRICHD and SADHART trials highlighted that depressive symptoms after MI independently predicted mortality and recurrent ischemic events even after adjusting for baseline cardiac severity.⁶˒⁷

Anxiety, traditionally viewed as a transient post-MI reaction, has likewise been associated with elevated catecholamines, increased heart rate variability reduction, and poorer rehabilitation adherence.⁸ Emerging evidence suggests that persistent anxiety confers risk similar to or exceeding that of depression for adverse cardiovascular outcomes.⁹ However, findings across populations have varied due to heterogeneity in assessment tools, timing, and follow-up.¹⁰ In South Asian populations, where the burden of CAD is substantial and psychosocial stressors are unique, there is limited data on the prognostic significance of combined depression-anxiety.¹¹

The biopsychosocial model of CAD underscores the need to recognize mental health comorbidities not merely as epiphenomena but as integral pathophysiological contributors.¹² Professional societies such as the American Heart Association (AHA) have recommended routine depression screening in all cardiac patients using validated instruments like the Patient Health Questionnaire-9 (PHQ-9) or Hospital Anxiety and Depression Scale (HADS).¹³ Despite such guidelines, psychiatric evaluation remains inconsistent in routine cardiology practice, particularly in resource-limited settings.¹⁴

This study therefore aimed to prospectively examine whether baseline depressive and anxiety symptoms independently predict major adverse cardiac events (MACE) within one year in patients with angiographically confirmed CAD. We hypothesized that patients with elevated baseline HADS-D or HADS-A scores would exhibit higher rates of MACE, independent of traditional cardiovascular risk factors and baseline left ventricular ejection fraction (LVEF). The study further explored the additive impact of comorbid depression and anxiety on outcome trajectories, emphasizing the necessity for integrated psycho-cardiac care.

A prospective observational cohort study was conducted at the Department of Cardiology and Psychiatry of a tertiary-care hospital between January 2023 and March 2025.

Participants:
A total of 250 consecutive adult patients (aged ≥ 40 years) with angiographically confirmed CAD (≥50% stenosis in at least one major coronary artery) were recruited following stabilization from acute events.

Inclusion Criteria:

• Diagnosed CAD (chronic stable angina, unstable angina, or post-MI state).
• Clinically stable ≥2 weeks post-event.
• Ability to provide informed consent and complete psychometric evaluation.

Exclusion Criteria:

• Known major psychiatric disorder other than depression/anxiety (e.g., psychosis, bipolar disorder).
• Cognitive impairment (MMSE < 24).
• Terminal illness or malignancy.
• Recent cardiac surgery (<3 months).
• Chronic corticosteroid or psychotropic drug use other than antidepressants.

Assessment Tools:

• Hospital Anxiety and Depression Scale (HADS): Subscales ≥8 defined clinically significant anxiety (HADS-A) or depression (HADS-D).
• Cardiac evaluation: Baseline echocardiography for LVEF, lipid profile, fasting glucose, and inflammatory markers (CRP).
• Outcome Definition: Major adverse cardiac events (MACE) included cardiovascular death, non-fatal MI, revascularization, or hospitalization for heart failure.

Follow-up:
Patients were followed at 3-, 6-, and 12-month intervals through clinic visits or telephonic contact. MACE were adjudicated by blinded cardiologists using standardized definitions.

Statistical Analysis:

Continuous variables are presented as mean ± SD and categorical variables as proportions. Between-group differences were assessed using t-tests or χ² tests. Kaplan–Meier survival analysis compared MACE-free survival across depression/anxiety strata. Cox proportional hazards regression determined independent predictors adjusting for age, sex, BMI, smoking, diabetes, hypertension, dyslipidemia, and LVEF. A p < 0.05 was considered statistically significant. Analyses were performed using SPSS v28.0.

Ethics:
Institutional Ethics Committee approval was obtained (Ref No. IEC/2023/184). Written informed consent was provided by all participants.

Table 1. Baseline Demographic and Clinical Profile (N = 250)

Population predominantly middle-aged men with moderate LV dysfunction.

Table 2. Prevalence of Psychological Symptoms

One-third had depression; two-fifths had anxiety; overlap significant.

Table 3. Distribution of MACE during 12-month Follow-up

Total 27.2% experienced at least one MACE; MI recurrence most frequent.

Table 4. MACE Incidence by Depression and Anxiety Status

MACE risk significantly higher in depression/anxiety groups, greatest in combined cases.

Table 5. Multivariate Cox Regression Predictors of MACE

Depression and anxiety remain independent predictors after adjusting for confounders.

Table 6. Kaplan–Meier Estimated 12-Month MACE-Free Survival

Co-occurrence of depression and anxiety substantially reduced MACE-free survival.

This study demonstrates that depressive and anxiety symptoms are common in CAD and serve as strong, independent predictors of major adverse cardiac events within one year of follow-up. Approximately 35% of patients met HADS-D criteria for depression and 41% for anxiety—rates consistent with previous post-MI and stable CAD cohorts.¹⁵˒¹⁶ The observed two-fold increase in MACE risk among depressed individuals corroborates earlier longitudinal studies.¹⁷˒¹⁸

Mechanistically, depression may accelerate atherothrombosis via heightened inflammatory cytokines (IL-6, TNF-α), platelet activation, and reduced vagal tone, while anxiety contributes to sympathetic overactivity and arrhythmogenic susceptibility.¹⁹˒²⁰ The additive hazard of comorbid depression-anxiety (HR = 2.85) suggests synergistic physiological stress, amplifying cardiovascular risk beyond either condition alone. These findings support a psychocardiologic continuum where chronic emotional distress influences both disease onset and progression.²¹

Comparable data were reported by Frasure-Smith et al., showing depression post-MI doubled mortality independent of LVEF.²² In the MIND-IT trial, depression predicted cardiac mortality across varying clinical severities.²³ Likewise, the COPES and TRIUMPH studies found anxiety associated with recurrent ischemia and increased rehospitalization.²⁴˒²⁵ Recent meta-analyses encompassing >30 000 participants confirmed depression conferred 1.8× higher risk of MACE in CAD, while anxiety increased risk by ~1.5×.²⁶

Regional data from Indian and Southeast Asian populations echo similar trends though confounded by socioeconomic stress and under-recognition of psychiatric illness.²⁷ Routine psychological screening is rarely integrated in cardiology clinics, despite AHA 2017 scientific statements advocating assessment of depression as a standard of care.²⁸ Our results reinforce that simple self-report tools such as HADS can identify high-risk subgroups warranting early psychosocial or pharmacologic intervention.

From a therapeutic perspective, antidepressant therapy (particularly SSRIs like sertraline) has demonstrated cardiac safety and potential improvement in adherence and HRV.²⁹ Psychotherapeutic modalities—cognitive-behavioral therapy, mindfulness-based stress reduction, and collaborative care—reduce depressive burden and may indirectly lower cardiac risk factors.³⁰ Multidisciplinary “cardio-psychiatry clinics” integrating cardiologists, psychiatrists, and psychologists represent an emerging model to optimize holistic outcomes.³¹

Limitations: single-center design, modest sample size, reliance on HADS without diagnostic interviews, and 12-month follow-up. Residual confounding (e.g., inflammatory biomarkers, medication adherence) cannot be excluded. Nonetheless, strengths include prospective design, standardized MACE adjudication, and adjustment for key covariates.

Implications: Integrating mental-health assessment into CAD management could enhance prognostication and secondary prevention strategies. Depression and anxiety should be recognized as modifiable risk factors comparable to hypertension or dyslipidemia.

Depressive and anxiety symptoms are highly prevalent in coronary artery disease and independently predict major adverse cardiac events. Their coexistence markedly worsens prognosis. Systematic psychological screening and integrated management should form an essential component of comprehensive cardiac care to improve long-term survival and quality of life.

1. Lichtman JH et al. Depression and Coronary Heart Disease: 2018 Update. 2018;137(20):e673-e692. doi:10.1161/CIR.0000000000000596
2. Hare DL et al. Depression and Cardiovascular Disease: A Clinical Review. Eur Heart J. 2023;44(4):345-357. doi:10.1093/eurheartj/ehac638
3. Smolderen KG et al. Anxiety Disorders and Outcomes after Acute Myocardial Infarction. Circ Cardiovasc Qual Outcomes. 2020;13(8):e006857. doi:10.1161/CIRCOUTCOMES.119.006857
4. Vaccarino V et al. Inflammation, Autonomic Dysfunction, and Depression in Heart Disease. Psychosom Med. 2019;81(1):1-9. doi:10.1097/PSY.0000000000000660
5. Carney RM, Freedland KE. Depression and Compliance with Medical Treatment in Heart Disease. 2017;318(8):745-746. doi:10.1001/jama.2017.10118
6. ENRICHD Investigators. Enhancing Recovery in Coronary Heart Disease Patients. 2003;289:3106-3116.
7. Glassman AH et al. Sertraline in Depressed Post-MI Patients (SADHART). 2002;288:701-709.
8. Celano CM, Huffman JC. Anxiety Disorders and Cardiovascular Disease. Curr Psychiatry Rep. 2021;23(6):38. doi:10.1007/s11920-021-01251-2
9. Meijer A et al. Prognostic Association of Anxiety after Myocardial Infarction. Br J Psychiatry. 2019;215(1):1-8. doi:10.1192/bjp.2018.283
10. Nicholson A et al. Psychological Distress and Cardiac Outcomes: Meta-analysis. Eur Heart J. 2018;39(4):389-397. doi:10.1093/eurheartj/ehx604
11. Prabhakaran D et al. Psychosocial Stress and CAD in South Asia. Nat Rev Cardiol. 2022;19(3):191-202. doi:10.1038/s41569-021-00644-y
12. Rozanski A et al. The Psychobiology of Cardiovascular Risk. Nat Rev Cardiol. 2019;16(7):394-409. doi:10.1038/s41569-019-0175-3
13. Carney RM, Freedland KE. Treating Depression to Improve Survival in Coronary Heart Disease. Heart Fail Clin. 2024;20(2):305-314. doi:10.1016/j.hfc.2023.10.011
14. Global prevalence of anxiety in adult cardiology outpatients: systematic review and meta-analysis. J Affect Disord. 2023;324:175-189. doi:10.1016/j.jad.2023.03.041
15. Anxiety disorder and cardiovascular disease: a two-sample Mendelian randomization and meta-analysis. ESC Heart Fail. 2024;11(2):1009-1021. doi:10.1002/ehf2.14676
16. Anxiety, a significant risk factor for coronary artery disease: 10-year prospective cohort. BMC Psychiatry. 2024;24(1):257. doi:10.1186/s12888-024-05798.