# The Mental Health–Acute Coronary Syndrome Continuum: Bidirectional Pathophysiological Links and Clinical Implications

**Authors:** Alexandra Herlaș-Pop, Andrei-Flavius Radu, Ada Radu, Gabriela S. Bungau, Delia Mirela Tit, Elena Emilia Babes, Cristiana Bustea

PMC · DOI: 10.3390/medsci14010138 · Medical Sciences · 2026-03-16

## TL;DR

This paper explores the two-way relationship between mental health disorders and heart attacks, showing how they influence each other and suggesting integrated care for better outcomes.

## Contribution

The paper provides a comprehensive review of bidirectional pathophysiological links and clinical implications between mental health disorders and acute coronary syndromes.

## Key findings

- Mental health disorders are highly prevalent in acute coronary syndrome populations and predict worse outcomes.
- Shared mechanisms include inflammation, autonomic imbalance, and endothelial dysfunction.
- Integrated care models improve psychological outcomes in cardiac patients.

## Abstract

Mental health disorders (MHDs) and acute coronary syndromes (ACSs) demonstrate reciprocal pathophysiological connections with substantial prognostic implications. Despite robust evidence linking MHDs to adverse cardiovascular outcomes, the bidirectional relationship remains inadequately characterized in clinical practice, with limited integration of mental health screening into routine cardiac care pathways. The present narrative review comprehensively presents contemporary data on epidemiology, shared biological mechanisms, clinical consequences, and integrated management strategies across the MHD–ACS continuum. A synthesis of peer-reviewed literature, meta-analyses, observational cohorts, randomized trials, and international guideline documents was performed, focusing on depression, anxiety, post-traumatic stress disorder, bipolar disorder, schizophrenia, and suicidality in relation to ACSs. MHDs are highly prevalent in ACS populations and independently predict increased mortality, major adverse cardiac events, and poorer functional recovery. Shared mechanisms include chronic low-grade inflammation, autonomic imbalance, hypothalamic–pituitary–adrenal axis hyperactivation, platelet hyperreactivity, and endothelial dysfunction. Selective serotonin reuptake inhibitors and cognitive behavioral therapy demonstrate the strongest evidence for treating depression in cardiac populations. Collaborative, stepped-care, and integrated cardiac rehabilitation models consistently improve psychological outcomes, with variable effects on cardiovascular endpoints. MHDs and ACSs form a self-reinforcing clinical continuum. Routine mental health screening and integrated cardio-psychiatric care represent essential components of secondary prevention and long-term outcome optimization.

## Linked entities

- **Diseases:** acute coronary syndromes (MONDO:0005542), depression (MONDO:0002050), anxiety (MONDO:0005618), post-traumatic stress disorder (MONDO:0005146), bipolar disorder (MONDO:0004985), schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, PF4 (platelet factor 4) [NCBI Gene 5196] {aka CXCL4, PF-4, SCYB4}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, SLC6A4 (solute carrier family 6 member 4) [NCBI Gene 6532] {aka 5-HTT, 5-HTTLPR, 5HTT, HTT, OCD1, SERT}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, TDO2 (tryptophan 2,3-dioxygenase) [NCBI Gene 6999] {aka HYPTRP, TDO, TO, TPH2, TRPO}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, GPHA2 (glycoprotein hormone subunit alpha 2) [NCBI Gene 170589] {aka A2, GPA2, ZSIG51}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HTR2A (5-hydroxytryptamine receptor 2A) [NCBI Gene 3356] {aka 5-HT2A, HTR2}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, PPBP (pro-platelet basic protein) [NCBI Gene 5473] {aka B-TG1, Beta-TG, CTAP-III, CTAP3, CTAPIII, CXCL7}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, HTR2C (5-hydroxytryptamine receptor 2C) [NCBI Gene 3358] {aka 5-HT1C, 5-HT2C, 5-HTR2C, 5HTR2C, HTR1C}, HTR1A (5-hydroxytryptamine receptor 1A) [NCBI Gene 3350] {aka 5-HT-1A, 5-HT1A, 5HT1a, ADRB2RL1, ADRBRL1, G-21}, GP6 (glycoprotein VI platelet) [NCBI Gene 51206] {aka BDPLT11, GPIV, GPVI}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, ERG (ETS transcription factor ERG) [NCBI Gene 2078] {aka LMPHM14, erg-3, p55}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}
- **Diseases:** occlusive (MESH:D001157), acute myocardial infarction (MESH:D009203), sudden cardiac death (MESH:D016757), chest pain (MESH:D002637), ischemic (MESH:D002545), orthostatic hypotension (MESH:D007024), MHDs (OMIM:603663), viral infection (MESH:D014777), sinus bradycardia (MESH:D012804), angina (MESH:D000787), coagulation (MESH:D001778), metabolic (MESH:D008659), sinus tachycardia (MESH:D013616), insomnia (MESH:D007319), loss (MESH:D016388), PTSD (MESH:D013313), trauma-related symptoms (MESH:D000068099), concentration difficulties (MESH:C567712), bipolar (MESH:D001714), Benign palpitations (MESH:D009369), ventricular fibrillation (MESH:D014693), GAD-2 (MESH:D020803), somatic disease (MESH:D013001), low (MESH:D009800), tissue injury (MESH:D017695), ENRICHD (MESH:D003327), anhedonia (MESH:D059445), appetite (MESH:D001068), hypercholesterolemic (MESH:D006938), myocardial hypertrophy (MESH:D006984), hypertension (MESH:D006973), calcification (MESH:D002114), psychomotor alterations (MESH:D011596), cardiotoxic (MESH:D066126), fear of death (MESH:C000719207), GAD-7 (MESH:C000726808), heart failure (MESH:D006333), cardiovascular, metabolic, immune, and psychiatric disorders (MESH:D024821), fatigue (MESH:D005221), Autonomic Nervous System (MESH:D001342), flu-like symptoms (MESH:D007251), necrotic (MESH:D009336), hyperlipoproteinemia (MESH:D006951), COVID-19 (MESH:D000086382), social phobia (MESH:D000072861), ischemic heart disease (MESH:D017202), Anxiety (MESH:D001007), occlusive thrombosis (MESH:D013927), Inflammation (MESH:D007249), homeostasis (MESH:D008232), LV (MESH:D018487), MINOCA (MESH:D000088442), Suicidal Ideation (MESH:D001072), vomiting (MESH:D014839), MH (MESH:C535694), Endothelial Dysfunction (MESH:D014652), HPA axis dysregulation (MESH:D007029), ventricular tachycardia (MESH:D017180), cap failure (MESH:D051437), arrhythmia (MESH:D001145)
- **Chemicals:** citalopram (MESH:D015283), sodium (MESH:D012964), risperidone (MESH:D018967), mirtazapine (MESH:D000078785), serotonin (MESH:D012701), quinolinic acid (MESH:D017378), Colchicine (MESH:D003078), docosahexaenoic acid (MESH:D004281), oxcarbazepine (MESH:D000078330), gabapentin (MESH:D000077206), ROS (MESH:D017382), haloperidol (MESH:D006220), puerarin (MESH:C033607), acetylsalicylic acid (MESH:D001241), lorazepam (MESH:D008140), metyrapone (MESH:D008797), kynurenine (MESH:D007737), eicosapentaenoic acid (MESH:D015118), carbamazepine (MESH:D002220), corticosterone (MESH:D003345), baicalein (MESH:C006680), Quetiapine (MESH:D000069348), aldosterone (MESH:D000450), tanshinone IIA (MESH:C021751), Lithium (MESH:D008094), dopamine (MESH:D004298), fluoxetine (MESH:D005473), Sertraline (MESH:D020280), venlafaxine (MESH:D000069470), quercetin (MESH:D011794), S-adenosyl-L-methionine (MESH:D012436), tirofiban (MESH:D000077466), aripiprazole (MESH:D000068180), Cortisol (MESH:D006854), thromboxane B2 (MESH:D013929), calcium (MESH:D002118), gamma-aminobutyric acid (MESH:D005680), NO (MESH:D009569), P2Y12 (-), cholesterol (MESH:D002784), Thioridazine (MESH:D013881), Clozapine (MESH:D003024), oxygen (MESH:D010100), Ziltivekimab (MESH:C000718191), escitalopram (MESH:D000089983), Lamotrigine (MESH:D000077213), lurasidone (MESH:D000069056), catecholamine (MESH:D002395), canakinumab (MESH:C541220), potassium (MESH:D011188), Benzodiazepines (MESH:D001569), dexamethasone (MESH:D003907), ADP (MESH:D000244), kaempferol (MESH:C006552), Cangrelor (MESH:C117446), trazodone (MESH:D014196), oxazepam (MESH:D010076), tryptophan (MESH:D014364), Valproate (MESH:D014635), paroxetine (MESH:D017374)
- **Species:** Hypericum perforatum (species) [taxon 65561], Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Full text

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## References

250 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028198/full.md

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Source: https://tomesphere.com/paper/PMC13028198