Modification of Associations Between PM2.5 and Vital Signs by β-Blocker Prescription Status Among Individuals with Heart Failure
Fine particulate matter (PM2.5) is associated with cardiovascular morbidity, particularly among individuals with pre-existing conditions such as heart failure (HF). β-blockers may modify the association between PM2.5 and health outcomes as they act on similar physiologic pathways as PM2.5. Using electronic health records (EHRs) from 26,653 individuals with HF observed from 2014-2016, we examined if associations between heart rate (HR) and PM2.5 were modified by prescription of β-blocker medication. Daily PM2.5 was modeled using ensemble machine learning models and matched to study participants based on the patient’s primary residence. Linear mixed models were adjusted for age, sex, race, smoking status, temperature, relative humidity, census sociodemographic variables, and a cubic spline term for time since start. We examined 0-4-day lags as well as the 5-day moving average. We stratified observations based on the date of β-blocker medication prescription to understand differences in associations between PM2.5 and HR and quantified these differences using a multiplicative interaction model. We also utilized data from an in vivo toxicological study to validate results from the epidemiologic data using a causal study design as well as examine additional outcomes not available in the EHR data. Results are given per 10 µg/m3 increase in PM2.5. Associations across lags were consistent. For the 5-day moving average, we observed a positive association between PM2.5 and HR (0.87, CI = 0.74, 1.00) for observations occuring with no prior β-blocker prescription. After prescription of a β-blocker we observed an inverse association between HR and 5-day average PM2.5 (-0.17, CI = -0.24, -0.11; Pinteraction = 1.47x10-23). This observation was mirrored in an in vivo rat study of diesel exhaust exposure and β-blocker prescription. In heart rate variability data available in the in vivo models but not the EHRs, only the RR interval was associated with interactions between β-blockers and diesel exhaust exposure. In conclusion, β-blocker usage likely attenuates associations between short-term PM2.5 and HR. Accounting for this in future studies may reveal novel means of reducing PM2.5-related cardiovascular morbidity and reduce confounding in population with high rates of β-blocker usage.