Front Neurosci. 2026 Sep 9;20:1942262. doi: 10.3389/fnins.2026.1942262. eCollection 2026.
ABSTRACT
Coronary heart disease (CHD) is commonly conceptualized as a disorder of atherosclerotic plaque burden, myocardial oxygen supply-demand mismatch and thrombosis. This framework remains indispensable, yet it does not fully explain stress-induced ischemia, persistent symptoms in the absence of obstructive lesions, or neuropsychiatric and cognitive sequelae after acute coronary events. Evidence increasingly indicates that CHD is embedded in a bidirectional brain-heart axis in which central autonomic, neuroendocrine, immune, vascular, metabolic, sleep-circadian and extracellular vesicle-mediated signals interact over time. In the brain-to-heart direction, psychological stress and altered activity within central autonomic networks may promote sympathetic activation, vagal withdrawal, hypothalamic-pituitary-adrenal signaling, endothelial dysfunction, platelet activation, coronary microvascular dysregulation and inflammatory acceleration of atherosclerosis. Mental stress-induced myocardial ischemia is a clinically relevant example of this top-down pathway and has been associated with adverse outcomes in patients with established CHD. In the heart-to-brain direction, coronary ischemia and myocardial infarction may affect brain function through visceral afferent signaling, systemic and neuroinflammation, cerebral hypoperfusion, blood-brain barrier disruption and cardiac extracellular vesicles. These processes may contribute to depression, anxiety, cognitive impairment and altered interoceptive control after acute coronary events, thereby creating feedback loops that can worsen cardiovascular risk. This review critically synthesizes clinical, observational, neuroimaging, and experimental evidence concerning CHD as a bidirectional brain-heart axis disorder. We distinguish established clinical associations from emerging mechanistic pathways, highlight major methodological limitations and unresolved controversies, and discuss the current level of evidence supporting candidate biomarkers and therapeutic strategies. We argue that future CHD management should complement plaque- and ischemia-oriented strategies with assessment of autonomic function, mental health, inflammatory tone, sleep-circadian biology, cerebrovascular health and neuroimmune signaling. Such integration may help identify patients whose risk is driven not only by coronary anatomy, but also by maladaptive brain-heart communication.
PMID:42781292 | PMC:PMC13598662 | DOI:10.3389/fnins.2026.1942262