Abstract

Loneliness has emerged as a significant and independent risk factor for cardiovascular disease (CVD), with epidemiological studies reporting an estimated 15%–30% increased risk across diverse populations and settings. This review synthesizes current evidence linking loneliness to major cardiovascular outcomes including coronary artery disease, heart failure, stroke, and all-cause mortality. This review is organized using a bio-psycho-social framework, examining biological mechanisms, psychological vulnerability, and social determinants contributing to cardiovascular risk. Within this framework, we examine biological mechanisms underlying this association, including chronic activation of stress response systems (hypothalamic–pituitary–adrenal axis and sympatho-adrenomedullary system), endothelial dysfunction, systemic inflammation, oxidative stress, and sleep disturbances. Among patients with established CVD, loneliness is highly prevalent (36%–45%) and associated with poor prognosis, reduced treatment adherence, and lower cardiac rehabilitation participation. We outline practical approaches for screening loneliness in clinical settings and discuss intervention strategies addressing social, emotional, and cognitive pathways. Recognition of loneliness as a modifiable cardiovascular risk factor represents an important opportunity for comprehensive patient care and secondary prevention strategies.