Unraveling the Brain-Heart Axis: More Than Inflammation.

Cardiovascular disease remains the leading cause of death worldwide, with a rising burden projected over the coming decades. Although traditional risk factors such as diabetes, hypertension, and dyslipidemia form the main targets of prevention strategies, many individuals carry a "residual" risk secondary to systemic inflammation which remains underrecognized. Landmark trials have established inflammation as a causal and modifiable driver of atherosclerotic cardiovascular disease. This review focuses on how inflammation can modulate interconnected diseases of the brain and heart. Growing evidence suggests that inflammation mediates a "brain-heart" axis, linking psychological stress, neuroinflammation, and cardiovascular pathology. Observational and mechanistic studies demonstrate that stress-induced neural activity, particularly within the amygdala, is associated with hematopoietic activation, arterial inflammation, and increased cardiovascular events. Models such as Takotsubo's cardiomyopathy and stroke-heart syndrome illustrate how acute brain injury can precipitate cardiovascular dysfunction via autonomic and inflammatory pathways. More recently, molecular imaging studies have provided direct evidence of stress-associated amygdalar activity being associated with both cardiovascular outcomes and cancer prognosis. This emerging framework reframes the brain and heart as interdependent organs connected through inflammatory and neurobiological processes, highlighting the potential for novel therapeutic targets, including modulation of stress-related neural pathways, alongside established anti-inflammatory strategies. Future directions include refinement of targeted therapies, use of advanced molecular imaging, and mechanistic studies to better delineate the pathways linking stress, inflammation, and cardiovascular disease.