A nationwide population-based study investigating the cardiovascular effects of exposure to particulate matter α-, β-, and γ-activities and individual radionuclides - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the U.S., and numerous studies have linked CVD to short- and long-term exposures to particulate air pollution (PM), however, the PM properties responsible for its toxicity are still not fully understood. Recently, we reported associations between PM gross β- activity and CVD mortality, blood pressure, oxidative stress, and lung and cardiac function. The primary source of ambient PM radioactivity (PR) in the U.S. is Rn gas, specifically its decay products (radionuclides) which can attach to ambient PM, and after inhalation, release ionizing radiation (α-, β-, and γ-radiation) inside the human body (internal dose). Although many studies have reported the effects of Rn decay products on cancer risk, we know very little about the non-cancer health effects of PR. The goal of this proposal is to investigate the effects of short- and long-term PR exposures on cardiovascular mortality and morbidity on a national scale and in a systematic way using a spectrum of PR exposure metrics, and determine whether PR exposure intensifies PM toxicity. To do this we have put together a large collection of PR measures. Using data from the U.S. EPA Radiation Network (RadNet), in Aim 1 we will assess the acute effects of short-term PR exposure, as measured by PM β-activity in 163 cities for the years 1987-2018, and PM γ-activities (35 cities for 2006-2018) on individual CVD admissions among Medicare enrollees and all ages CVD mortality. In Aim 2 we will examine the chronic effects of long-term PM β- and γ-activities on CVD admissions. In Aim 3, in the four U.S. cities with U.S. Nuclear Weapons Non-Proliferation Treaty sites in 2000-2018, we will estimate the acute and chronic effects of exposure to individual radionuclides on CVD admissions and mortality. In three U.S. cities (Aim 4) we will measure daily exposures to PM α-activity associated with short-lived radionuclides using a newly developed continuous monitor, and in one city we will estimate daily exposures to PM α-activity from long-lived radionuclides using archived and newly collected filters. Using these data we will then assess the acute effects of short-term exposures to PM2.5 gross α-activity associated with long-lived radionuclides and short-lived radionuclides on CVD admissions and mortality. In all aims, we will examine seasonal and regional variability, confounding by PM2.5, exposure-response, timing of exposure, effect modification by individual and area level risk factors and apply both traditional and causal inference methods to address confounding. This will be the first study to provide rigorous scientific evidence of the cardiovascular effects of radioactive particles in a national population-based study, and to describe the CVD effects of PM α-activity. Investigations based on both Medicare and mortality data will make conclusions generalizable to the entire U.S. population. Because exposures to PR are ubiquitous, our findings may have important implications for environmental and public health policies. Improving our understanding of the factors influencing PM toxicity is critical to developing cost-effective air quality standards to protect public health.
