Preexisting multimorbidity predicts greater mortality risks related to long-term PM_2.5 exposure

Long-term health risk assessments related to ambient fine particulate matter (PM_2.5) exposure have been more limited to general population but not towards individuals suffering from multimorbidity. While both multimorbidity and PM_2.5 are independently linked to elevated mortality risk, their combined effects and interactions remain practically unexplored. A cross-cohort analysis was undertaken on data from 3 prospective cohorts, initially enrolling 869038 adults aged ≥18 years followed up during 2005-2022. Multimorbidity was identified at baseline surveys through a list of nine common chronic conditions. Cox proportional hazards models were utilized to quantify the associations of long-term PM_2.5 exposure with all-cause, cardiovascular, and respiratory mortality among individuals with and without multimorbidity. Joint effects and interactions between baseline multimorbidity and PM_2.5 level on the additive and multiplicative scales were examined. Risk differences of PM_2.5-induced mortality were analyzed stratified by number of chronic conditions and multimorbidity patterns. Subgroup and sensitivity analyses were carried out to evaluate the consistency of the findings. Among 713119 eligible participants for primary analysis, 65490 prevalent cases of multimorbidity were identified at baseline over a median follow-up of 12.2 years. Compared to individuals without multimorbidity, associations of PM_2.5 exposure with all-cause and cardiovascular mortality were more prominent among multimorbidity individuals (P <0.05 for heterogeneity). Our analysis unveiled a significant additive interaction between PM_2.5 level and preexisting multimorbidity status, yielding estimated attributable proportions of 11.7%-17.8% and excess risks of 31.1%-72.6% for different mortality outcomes. Sex subgroup and sensitivity analyses consistently produced similar results. This large-scale multicohort analysis demonstrated markedly stronger associations between PM_2.5 levels and risks of all-cause and cardiovascular mortality in multimorbidity populations compared to those without multimorbidity. PM_2.5 exposure and preexisting multimorbidity showed synergistic effects in triggering mortality events, wherein the joint risks were intensified with elevated PM_2.5 levels and an increased number of chronic conditions.