Integrating Emotional Stress and Lipid Lowering in Cardiovascular Disease Management: The Future of Precision Cardiovascular Prevention

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.

Keywords: cardiovascular disease; digital health; emotional stress; endothelial dysfunction; lipid-lowering therapy; precision prevention; psychosocial factors; residual risk.

Figure 1

The Emotion–Lipid Synergy Model. Lipid retention initiates atherosclerotic plaque formation, providing the biological substrate for disease. Emotional stress—including anger, grief, and chronic psychosocial strain—triggers sympathetic activation, HPA axis dysregulation, and inflammatory cascades. These processes converge on endothelial dysfunction, oxidative stress, and heightened platelet reactivity, collectively amplifying the risk of plaque rupture and acute cardiovascular events, even in patients with well-controlled LDL-C.