Associations of urban heat island and its metabolomic profiles with all-cause and cause-specific mortality in middle-aged and older adults

To investigate associations between urban heat island (UHI) exposure and mortality outcomes in urban residents, and to identify metabolic pathways mediating these relationships. This prospective cohort study included 233,137 urban-dwelling middle-aged and older adults from the UK Biobank between 2006 and 2010. UHI exposure was estimated using satellite-derived land surface temperature data. Mortality outcomes were identified through national death registry records. Cox proportional hazards models assessed associations between long-term UHI exposure and mortality risk. Elastic net regression identified key metabolites related to exposure, followed by mediation analyses to quantify their mechanistic contributions and interaction analyses to examine how they modify the UHI-mortality relationship. Long-term UHI exposure was significantly associated with increased risk of all-cause mortality (HR: 1.05, 95% CI: 1.04–1.06), with the strongest associations observed for endocrine system diseases (HR: 1.08, 95% CI: 1.06–1.11) and respiratory diseases (HR: 1.08, 95% CI: 1.06–1.10). Glucose emerged as the strongest mediator, explaining 31.7% of the UHI effect on all-cause mortality. Interaction analyses revealed that metabolite levels modified UHI-mortality associations, particularly for endocrine diseases. UHI exposure significantly increases mortality risk among urban residents, with glucose and lipid serving as key biological mediators. These findings emphasize the importance of integrating climate resilience into urban planning and highlight potential targets for interventions to protect vulnerable populations from heat-related health impacts. • Urban heat island exposure increases all-cause and cause-specific mortality risk. • Machine learning identifies 47 metabolites linked to urban heat exposure. • Urban heat alters amino acid and lipid metabolism pathways. • Glucose mediates 16% of the urban heat island effect on all-cause mortality. • Metabolites modify urban heat mortality risks, especially for endocrine diseases.