J Clin Med. 2025 Oct 13;14(20):7208. doi: 10.3390/jcm14207208.
ABSTRACT
Residual cardiovascular risk remains substantial despite widespread adoption of intensive lipid-lowering strategies-statins, PCSK9 inhibitors, and RNA-based agents-that achieve very low LDL-C and apoB levels. Over the past three years, converging epidemiologic and mechanistic evidence has highlighted emotional stress-including anger, grief, anxiety, and chronic psychosocial strain-as a biologically active determinant of atherosclerotic disease and a frequent trigger of acute events. We propose the Emotion-Lipid Synergy Model, in which lipid burden establishes the atherothrombotic substrate while emotion-driven autonomic and vascular perturbations amplify endothelial dysfunction, microvascular constriction, inflammation, and thrombogenicity-thereby widening the residual-risk gap even when lipid targets are met. From this perspective, prevention should evolve toward precision psychocardiology: systematically screening for distress and stress reactivity; leveraging wearables to detect high-risk emotional states; and delivering timely, scalable, just-in-time behavioral interventions alongside guideline-directed lipid management. Particular attention is warranted for women and patients with angina and no obstructive coronary disease, who appear disproportionately susceptible to mental-stress ischemia. We outline a research agenda-flagship outcomes trials, mechanistic studies, and multimodal phenotyping-and discuss implementation pathways that integrate emotion metrics into cardiac rehabilitation and routine care. Integrating emotion assessment and modulation with lipid control offers a pragmatic route to reduce residual risk and advance equitable, personalized cardiovascular prevention.
PMID:41156076 | PMC:PMC12565168 | DOI:10.3390/jcm14207208