Bidirectional brain-heart communication in coronary heart disease: from coronary plaques to central autonomic networks

FIGURE 1. Bidirectional brain–heart axis model in coronary heart disease. This diagram places coronary heart problem (CHD) in a bidirectional brain-heart feedback system rather than as a disease of the internal heart wall. Stress-related, interoceptive, endocrine, nociceptive, cardiovascular reflex signals reach the central autonomic network, including cortical, limbic, hypothalamic and brainstem circuits, and affect coronary vulnerability through autonomic, hemodynamic, endothelial, platelet, microvascular and inflammatory processes. In the opposite direction, ischemic myocardium and diseased heart vessels send afferent neural and humoral signals to the brain via inflamed plaques, perivascular nerves, endothelium and immune cells, platelets, cardiomyocytes, and circulating mediators. The model focuses on a feedback loop between acute stress, vascular inflammation, hypoperfusion, cognitive impairments, heart failure and neuropsychiatric disorders. Solid, dashed, and dotted arrows indicate comparatively well-supported human evidence, predominantly associative human evidence, and preclinical or hypothesis-generating evidence, respectively. Arrowheads indicate the proposed direction of signal…

FIGURE 2. A vicious-cycle model of coronary heart disease brain-heart communication. This model illustrates how chronic stress, poor sleep, depression, metabolic dysfunction, and adverse social conditions may disrupt autonomic, endocrine, and inflammatory regulation, thereby promoting endothelial dysfunction, coronary microvascular dysfunction, and plaque inflammation. In turn, atherosclerotic plaques, ischemic myocardium, and inflamed vessels may send neural, immune, and metabolic signals to brainstem, limbic, cortical, and glial systems. Resulting anxiety, sympathetic activation, inflammation, sleep disturbance, inactivity, and poor adherence may further increase recurrent ischemia, adverse remodeling, persistent symptoms, and impaired quality of life. Conventional risk factors, including thrombosis, lipid burden, hypertension, diabetes, and smoking, remain central to this process. Solid, dashed, and dotted arrows indicate comparatively well-supported human evidence, predominantly associative human evidence, and preclinical or hypothesis-generating evidence, respectively. Arrowheads indicate the proposed direction of signal flow, and line style reflects evidence maturity rather than…

FIGURE 3. Translational mechanisms in the coronary heart disease brain-heart axis. Psychosocial stress may promote limbic, autonomic, inflammatory, and neuroimmune dysregulation, contributing to myocardial ischemia, endothelial dysfunction, arrhythmogenesis, and recurrent adverse outcomes. A phenotype-driven assessment combining autonomic, inflammatory, behavioral, stress-testing, and research imaging markers may guide targeted interventions, including cardiac rehabilitation, anti-inflammatory therapy, neuromodulation, extracellular vesicle-based strategies, and integrated multidisciplinary care, with the aim of improving symptoms, recovery, and long-term prognosis.