Social disconnection: From cortisol-oxytocin imbalance to endothelial dysfunction, a narrative review of mechanisms and potential interventions.

Social disconnection, both in the form of social isolation and loneliness, is increasingly recognized as a clinically significant but underappreciated risk factor for cardiovascular disease (CVD), affecting 16-25% of individuals. Population studies have consistently linked social disconnection to a higher risk of all-cause mortality, myocardial infarction, stroke, and cardiovascular death, yet routine screening for social disconnection is uncommon in everyday clinical practice. Even when identified, due to both lack of strong evidence-based interventions and awareness about them, meaningful clinical changes are seldom observed. In light of growing recognition by major health authorities, including the World Health Organization and the U.S. Surgeon General, and of the Harvard Study of Adult Development, showing that social integration and strong relationships are the most powerful predictors of healthy aging, we conducted a narrative literature review synthesizing current evidence on the relationship between social disconnection and CVD. The mechanism mediating social disconnection and cardiovascular events is still a matter of debate. We focus on cortisol-oxytocin imbalance and highlight that it is central in causing CVD through autonomic dysregulation, nutritional imbalance and gut microbiome alterations. Alongside psychosocial comorbidities, these factors may converge on endothelial dysfunction as an initiating mechanism of CVD. Our review also aims to foster discussion on how to recognize and address social disconnection in clinical practice, emphasizing the need for structured, multidisciplinary pathways as well as trials assessing their effect on improving both social disconnection and the associated CVD risk.