Applying a multistate survival model to explore the role of fine particles in promoting frailty in the Medicare cohort

Fine particle pollution is a well-established risk to human health. Observational epidemiology generally treats events as though they are independent of one another and so do not examine the role air pollution may play in promoting the progression of disease. Multistate survival models account for the complex pathway of disease to death. We employ a multistate survival model to characterize the role of chronic exposure to PM2.5 in affecting the rate at which Medicare beneficiaries transition to first hospitalization for cardiovascular disease and then subsequently death. We use an open cohort of Medicare beneficiaries and PM2.5 concentrations estimated with photochemical model predictions, satellite-based observations, land-use data, and meteorological variables. The multistate model included three transitions: (1) entry to cardiovascular hospital admission; (2) entry to death; and (3) cardiovascular hospital admission to death. The transition intensity was modeled using a Cox proportional hazards model. For a 1 µg/m3 increase in annual mean PM2.5, we estimate a nationally pooled hazard ratio of 1.022 (95% confidence interval [CI] = 1.018, 1.025) for the transition from entry to first cardiovascular hospital admission; 1.054 (95% CI = 1.039, 1.068) for the transition from entry to death; 1.036 (95% CI = 1.027, 1.044) for the transition from first cardiovascular hospital admission to death. The hazard ratios exhibited some heterogeneity within each of nine climatological regions and for each of the three transitions. We find evidence for the role of PM in both promoting chronic illness and increasing the subsequent risk of death.