A Narrative Review on the Impact of Air Pollution on Heart Failure Risk and Exacerbation.

Air pollution is a risk factor for many cardiovascular diseases, including heart failure (HF). Although the links between air pollution and HF have been explored, the results are scattered and difficult to piece together into a cohesive story. Therefore, we undertook a narrative review of all aspects of the relationship between HF and air pollution exposure, including risks of developing HF when exposed to air pollution, the exacerbation of HF symptoms by air pollution exposure, and the increased susceptibility that individuals with HF have for air pollution-related health risks. We also examined the literature on environmental justice as well as air pollution interventions for HF. We found substantial evidence linking air pollution exposure to HF incidence. There were a limited number of studies that examined air pollution exposure in clearly defined populations with HF to explore exacerbation of HF or the susceptibility of individuals with HF to air pollution health risks. However, there is substantial evidence that HF-related hospitalisations are increased under air pollution exposure and that the air pollution associated increase in HF-related hospitalisations is greater than hospitalisations for other chronic diseases, supporting links between air pollution and both exacerbation of HF and susceptibility of individuals with HF. There is emerging evidence for interventions that can decrease air pollution health risks for individuals with HF, and more studies are needed, particularly randomised controlled trials. Thus, although the air pollution-related health risks for HF incidence and hospitalisations are clear, further studies specifically targeted at identified data gaps will greatly improve our knowledge of the susceptibility of individuals with HF and interventions to reduce risks.

Exposures to low-levels of fine particulate matter are associated with acute changes in heart rate variability, cardiac repolarization, and circulating blood lipids in coronary artery disease patients.

Exposure to air pollution is a major risk factor for cardiovascular disease, disease risk factors, and mortality. Specifically, particulate matter (PM), and to some extent ozone, are contributors to these effects. In addition, exposures to these pollutants may be especially dangerous for susceptible populations. In this repeated-visit panel study, cardiovascular markers were collected from thirteen male participants with stable coronary artery disease. For 0-4 days prior to the health measurement collections, daily concentrations of fine PM (PM2.5) and ozone were obtained from local central monitoring stations located near the participant's homes. Then, single (PM2.5) and two-pollutant (PM2.5 and ozone) models were used to assess whether there were short-term changes in cardiovascular health markers. Per interquartile range increase in PM2.5, there were decrements in several heart rate variability metrics, including the standard deviation of the normal-to-normal intervals (lag 3, -5.8%, 95% confidence interval (CI) = -11.5, 0.3) and root-mean squared of successive differences (five day moving average, -8.1%, 95% CI = -15.0, -0.7). In addition, increases in PM2.5 were also associated with changes in P complexity (lag 1, 4.4%, 95% CI = 0.5, 8.5), QRS complexity (lag 1, 4.9%, 95% CI = 1.4, 8.5), total cholesterol (five day moving average, -2.1%, 95% CI = -4.1, -0.1), and high-density lipoprotein cholesterol (lag 2, -1.6%, 95% CI = -3.1, -0.1). Comparisons to our previously published work on ozone were conducted. We found that ozone affected inflammation and endothelial function, whereas PM2.5 influenced heart rate variability, repolarization, and lipids. All the health changes from these two studies were found at concentrations below the United States Environmental Protection Agency's National Ambient Air Quality Standards. Our results imply clear differences in the cardiovascular outcomes observed with exposure to the two ubiquitous air pollutants PM2.5 and ozone; this observation suggests different mechanisms of toxicity for these exposures.

Associations between short-term exposure to PM2.5 and cardiomyocyte injury in myocardial infarction survivors in North Carolina.

OBJECTIVE: Short-term ambient fine particulate matter (PM2.5) is associated with adverse cardiovascular events including myocardial infarction (MI). However, few studies have examined associations between PM2.5 and subclinical cardiomyocyte damage outside of overt cardiovascular events. Here we evaluate the impact of daily PM2.5 on cardiac troponin I, a cardiomyocyte specific biomarker of cellular damage. METHODS: We conducted a retrospective cohort study of 2924 patients identified using electronic health records from the University of North Carolina Healthcare System who had a recorded MI between 2004 and 2016. Troponin I measurements were available from 2014 to 2016, and were required to be at least 1 week away from a clinically diagnosed MI. Daily ambient PM2.5 concentrations were estimated at 1 km resolution and assigned to patient residence. Associations between log-transformed troponin I and daily PM2.5 were evaluated using distributed lag linear mixed effects models adjusted for patient demographics, socioeconomic status and meteorology. RESULTS: A 10 µg/m3 elevation in PM2.5 3 days before troponin I measurement was associated with 0.06 ng/mL higher troponin I (95% CI=0.004 to 0.12). In stratified models, this association was strongest in patients that were men, white and living in less urban areas. Similar associations were observed when using 2-day rolling averages and were consistently strongest when using the average exposure over the 5 days prior to troponin I measurement. CONCLUSIONS: Daily elevations in PM2.5 were associated with damage to cardiomyocytes, outside of the occurrence of an MI. Poor air quality may cause persistent damage to the cardiovascular system leading to increased risk of cardiovascular disease and adverse cardiovascular events.

Short-term PM2.5 exposure and early-readmission risk: a retrospective cohort study in North Carolina heart failure patients.

BACKGROUND: Short-term changes in ambient fine particulate matter (PM2.5) increase the risk for unplanned hospital readmissions. However, this association has not been fully evaluated for high-risk patients or examined to determine if the readmission risk differs based on time since discharge. Here we investigate the relation between ambient PM2.5 and 30-day readmission risk in heart failure (HF) patients using daily time windows and examine how this risk varies with respect to time following discharge. METHODS: We performed a retrospective cohort study of 17,674 patients with a recorded HF diagnosis between 2004 and 2016. The cohort was identified using the EPA CARES electronic health record resource. The association between ambient daily PM2.5 (µg/m3) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM2.5 associated readmission risk was examined throughout the 30-day readmission period and for early readmissions (1-3 days post-discharge). Models for 30-day readmissions included a parametric continuous function to estimate the daily PM2.5 associated readmission hazard. Fine-resolution ambient PM2.5 data were assigned to patient residential address and hazard ratios are expressed per 10 µg/m3 of PM2.5. Secondary analyses examined potential effect modification based on the time after a HF diagnosis, urbanicity, medication prescription, comorbidities, and type of HF. RESULTS: The hazard of a PM2.5-related readmission within 3 days of discharge was 1.33 (95% CI 1.18-1.51). This PM2.5 readmission hazard was slightly elevated in patients residing in non-urban areas (1.43, 95%CI 1.22-1.67) and for HF patients without a beta-blocker prescription prior to the readmission (1.35; 95% CI 1.19-1.53). CONCLUSION: Our findings add to the evidence indicating substantial air quality-related health risks in individuals with underlying cardiovascular disease. Hospital readmissions are key metrics for patients and providers alike. As a potentially modifiable risk factor, air pollution-related interventions may be enacted that might assist in reducing costly and burdensome unplanned readmissions.

Associations between neighborhood socioeconomic cluster and hypertension, diabetes, myocardial infarction, and coronary artery disease within a cohort of cardiac catheterization patients.

BACKGROUND: Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease and diabetes, but these associations are rarely studied across large, diverse populations. METHODS: We used Ward's Hierarchical clustering to define eight neighborhood clusters across North Carolina using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001 to 2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction, hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of North Carolina, distance to Duke University Hospital, and smoking status. RESULTS: Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of myocardial infarction in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations. CONCLUSIONS: We observed higher prevalence of cardiovascular disease and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.

Evaluation of PM2.5 air pollution sources and cardiovascular health.

Long-term air pollution exposure, notably fine particulate matter, is a global contributor to morbidity and mortality and a known risk factor for coronary artery disease (CAD) and myocardial infarctions (MI). Knowledge of impacts related to source-apportioned PM2.5 is limited. New modeling methods allow researchers to estimate source-specific long-term impacts on the prevalence of CAD and MI. The Catheterization Genetics (CATHGEN) cohort consists of patients who underwent a cardiac catheterization at Duke University Medical Center between 2002 and 2010. Severity of coronary blockage was determined by coronary angiography and converted into a binary indicator of clinical CAD. History of MI was extracted from medical records. Annual averages of source specific PM2.5 were estimated using an improved gas-constrained source apportionment model for North Carolina from 2002 to 2010. We tested six sources of PM2.5 mass for associations with CAD and MI using mixed effects multivariable logistic regression with a random intercept for county and multiple adjustments. PM2.5 fractions of ammonium bisulfate and ammonium nitrate were associated with increased prevalence of CAD (odds ratio [OR] 1.20; 95% CI = 1.11, 1.22 and OR 1.18; 95% CI = 1.05, 1.32, respectively). PM2.5 from ammonium bisulfate and ammonium nitrate were also associated with increased prevalence of MI (OR 1.20; 95% CI = 1.10, 1.29 and OR 1.35; 95% CI = 1.20, 1.53, respectively). Greater PM2.5 concentrations of ammonium bisulfate and ammonium nitrate are associated with greater MI and CAD prevalence. The association with bisulfate suggests aerosol acidity may play a role. Our findings suggest analyses of source specific PM2.5 mass can reveal novel associations.

Respiratory Impacts of Wildland Fire Smoke: Future Challenges and Policy Opportunities. An Official American Thoracic Society Workshop Report.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1) the science of wildland fire incidence and fire management, 2) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3) communication strategies to address these health risks, and 4) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Long-Term Exposure to Particulate Air Pollution Is Associated With 30-Day Readmissions and Hospital Visits Among Patients With Heart Failure.

Background Long-term air pollution exposure is a significant risk factor for inpatient hospital admissions in the general population. However, we lack information on whether long-term air pollution exposure is a risk factor for hospital readmissions, particularly in individuals with elevated readmission rates. Methods and Results We determined the number of readmissions and total hospital visits (outpatient visits+emergency room visits+inpatient admissions) for 20 920 individuals with heart failure. We used quasi-Poisson regression models to associate annual average fine particulate matter at the date of heart failure diagnosis with the number of hospital visits and 30-day readmissions. We used inverse probability weights to balance the distribution of confounders and adjust for the competing risk of death. Models were adjusted for age, race, sex, smoking status, urbanicity, year of diagnosis, short-term fine particulate matter exposure, comorbid disease, and socioeconomic status. A 1-µg/m3 increase in fine particulate matter was associated with a 9.31% increase (95% CI, 7.85%-10.8%) in total hospital visits, a 4.35% increase (95% CI, 1.12%-7.68%) in inpatient admissions, and a 14.2% increase (95% CI, 8.41%-20.2%) in 30-day readmissions. Associations were robust to different modeling approaches. Conclusions These results highlight the potential for air pollution to play a role in hospital use, particularly hospital visits and readmissions. Given the elevated frequency of hospitalizations and readmissions among patients with heart failure, these results also represent an important insight into modifiable environmental risk factors that may improve outcomes and reduce hospital use among patients with heart failure.

Association between short-term exposure to ambient fine particulate matter and myocardial injury in the CATHGEN cohort.

Exposure to fine particulate matter (PM2.5) has been associated with a higher risk for coronary events. Elevated circulating cardiac troponins (cTn) are suggestive of myocardial injury in both ischemic and non-ischemic conditions. However, little is known about the association between PM2.5 and cTn. In this study, we investigated short-term PM2.5 effects on cardiac troponin T (cTnT), as well as N-terminal-pro brain natriuretic peptide (NT-pro BNP) and inflammatory biomarkers among cardiac catheterized participants. We analyzed 7444 plasma cTnT measurements in 2732 participants who presented to Duke University Hospital with myocardial infarction symptoms between 2001 and 2012, partly along with measurements of NT-pro BNP and inflammatory biomarkers. Daily PM2.5 concentrations were predicted by a neural network-based hybrid model and were assigned to participants' residential addresses. We applied generalized estimating equations to assess associations of PM2.5 with biomarker levels and the risk of a positive cTnT test (cTnT > 0.1 ng/mL). The median plasma cTnT concentration at presentation was 0.05 ng/mL and the prevalence of a positive cTnT test was 35.4%. For an interquartile range (7.6 µg/m3) increase in PM2.5 on the previous day, cTnT concentrations increased by 7.7% (95% CI: 3.4-12.3) and the odds ratio of a positive cTnT test was 1.08 (1.01-1.16). Participants under 60 years (effect estimate: 15.2%; 95% CI: 7.4-23.5) or living in rural areas (12.3%; 95% CI: 4.8-20.3) were more susceptible. There was evidence for increases in fibrinogen and NT-pro BNP associated with elevated PM2.5 on the concurrent and previous two days. Our study suggests that acute PM2.5 exposure may elevate indicators of myocardial tissue damage. This finding substantiates the association of air pollution exposure with adverse cardiovascular events.

Association of short-term exposure to ambient PM2.5 with hospital admissions and 30-day readmissions in end-stage renal disease patients: population-based retrospective cohort study.

OBJECTIVES: To examine the effect of short-term exposure to ambient fine particulate matter (PM2.5) on all-cause, cardiovascular and respiratory-related hospital admissions and readmissions among patients receiving outpatient haemodialysis. DESIGN: Retrospective cohort study. SETTING: Inpatient hospitalisation claims identified from the US Renal Data System in 530 US counties. PARTICIPANTS: All patients receiving in-centre haemodialysis between 2008 and 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk of all-cause, cardiovascular and respiratory-related hospital admissions and 30-day all-cause and cause-specific readmission following an all-cause, cardiovascular, and respiratory-related discharges. Readmission risk was evaluated for early (1-7 days postdischarge) and late (8-30 days postdischarge) readmission time periods. Relative risk is expressed per 10 µg/m3 of PM2.5. RESULTS: Same-day ambient PM2.5 was associated with increased hospital admission risk for cardiovascular causes (0.9%, 95% CI 0.2 to 1.7). Greater PM2.5-related associations were observed with 30-day readmission risk. Early-readmission risk was increased by 1.6%-1.8% following all-cause (1.6%, 95% CI 0.6% to 2.6%), cardiovascular (1.8%, 95% CI 0.4% to 3.2%) and respiratory (1.8%, 95% CI 0.4% to 3.2%) discharges; while late-readmission risk increased by 1.2%-1.3% following all-cause and cardiovascular discharges. PM2.5-related associations with readmission risk were greatest for certain cause-specific readmissions ranging 4.0%-6.5% for dysrhythmia and conduction disorder, heart failure, chronic obstructive pulmonary disease, other non-cardiac chest pain or respiratory syndrome and pneumonia. Following all-cause discharges, the cause-specific early-readmission risk was increased by 6.5% (95% CI 3.5% to 9.6%) for pneumonia, 4.8% (95% CI 2.3% to 7.4%) for dysrhythmia and conduction disorder, 3.7% (95% CI 1.4% to 6.0%) for heart failure and 2.7% (95% CI 1.2% to 4.2%) for other non-cardiac chest pain or respiratory syndrome-related causes. CONCLUSIONS: Daily ambient PM2.5 was associated with an increased risk of cardiovascular admissions and 30-day readmissions following cardiopulmonary-related discharges in a vulnerable end-stage renal disease population. In the first week following discharge, greater PM2.5-related risk of rehospitalisation was identified for some diagnoses.

Cardiopulmonary Impact of Particulate Air Pollution in High-Risk Populations: JACC State-of-the-Art Review.

Fine particulate air pollution <2.5 µm in diameter (PM2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.

Accelerated epigenetic age as a biomarker of cardiovascular sensitivity to traffic-related air pollution.

BACKGROUND: Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures. METHODS: Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status. RESULTS: We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5. CONCLUSION: Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.

Wildfire Smoke: Opportunities for Cooperation Among Health Care, Public Health, and Land Management to Protect Patient Health.

Preventing the adverse health impacts of wildfire smoke involves helping people understand if they are at risk, and the actions they can take to limit exposure. Cooperation between land managers, public health officials, and the health care system could alert the public to take actions that reduce wildfire smoke-related health risks.

Out-of-Hospital Cardiac Arrests and Wildfire-Related Particulate Matter During 2015-2017 California Wildfires.

Background The natural cycle of large-scale wildfires is accelerating, increasingly exposing both rural and populous urban areas to wildfire emissions. While respiratory health effects associated with wildfire smoke are well established, cardiovascular effects have been less clear. Methods and Results We examined the association between out-of-hospital cardiac arrest and wildfire smoke density (light, medium, heavy smoke) from the National Oceanic Atmospheric Association's Hazard Mapping System. Out-of-hospital cardiac arrest data were provided by the Cardiac Arrest Registry to Enhance Survival for 14 California counties, 2015-2017 (N=5336). We applied conditional logistic regression in a case-crossover design using control days from 1, 2, 3, and 4 weeks before case date, at lag days 0 to 3. We stratified by pathogenesis, sex, age (19-34, 35-64, and ≥65 years), and socioeconomic status (census tract percent below poverty). Out-of-hospital cardiac arrest risk increased in association with heavy smoke across multiple lag days, strongest on lag day 2 (odds ratio, 1.70; 95% CI, 1.18-2.13). Risk in the lower socioeconomic status strata was elevated on medium and heavy days, although not statistically significant. Higher socioeconomic status strata had elevated odds ratios with heavy smoke but null results with light and medium smoke. Both sexes and age groups 35 years and older were impacted on days with heavy smoke. Conclusions Out-of-hospital cardiac arrests increased with wildfire smoke exposure, and lower socioeconomic status appeared to increase the risk. The future trajectory of wildfire, along with increasing vulnerability of the aging population, underscores the importance of formulating public health and clinical strategies to protect those most vulnerable.

Associations Between Long-Term Fine Particulate Matter Exposure and Mortality in Heart Failure Patients.

Background Environmental health risks for individuals with heart failure (HF) have been inadequately studied, as these individuals are not well represented in traditional cohort studies. To address this we studied associations between long-term air pollution exposure and mortality in HF patients. Methods and Results The study population was a hospital-based cohort of individuals diagnosed with HF between July 1, 2004 and December 31, 2016 compiled using electronic health records. Individuals were followed from 1 year after initial diagnosis until death or the end of the observation period (December 31, 2016). We used Cox proportional hazards models to evaluate the association of annual average fine particulate matter (PM2.5) exposure at the time of initial HF diagnosis with all-cause mortality, adjusted for age, race, sex, distance to the nearest air pollution monitor, and socioeconomic status indicators. Among 23 302 HF patients, a 1 µg/m3 increase in annual average PM2.5 was associated with an elevated risk of all-cause mortality (hazard ratio 1.13; 95% CI, 1.10-1.15). As compared with people with exposures below the current national PM2.5 exposure standard (12 µg/m3), those with elevated exposures experienced 0.84 (95% CI, 0.73-0.95) years of life lost over a 5-year period, an observation that persisted even for those residing in areas with PM2.5 concentrations below current standards. Conclusions Residential exposure to elevated concentrations of PM2.5 is a significant mortality risk factor for HF patients. Elevated PM2.5 exposures result in substantial years of life lost even at concentrations below current national standards.

A case-crossover analysis of the relationship of air pollution with out-of-hospital sudden unexpected death in Wake County, North Carolina (2013-2015).

Out-of-hospital sudden unexpected deaths are non-accidental deaths that occur without obvious underlying causes and may account for 10% of natural deaths before age 65. Short-term exposure to ambient air pollution is associated with all-cause (non-accidental) and cause-specific (e.g., cardiovascular) mortality, and with immediate exposures often yielding the highest magnitude risk estimates. Few studies have focused on short-term exposure to air pollution and sudden unexpected deaths. Using the University of North Carolina Sudden Unexpected Death in North Carolina population, we examine associations between short-term criteria air pollutant exposures with sudden unexpected deaths using a time-stratified case-crossover design, with data on criteria air pollutants from the Environmental Protection Agency's Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression with air pollutant exposures scaled to roughly inter-quartile ranges; models were adjusted for average temperature and relative humidity on event day and preceding 3 days. Potential for confounding by co-pollutants were examined in two pollutant models. ORs for PM2.5 at lag day 1 were elevated (adjusted OR for 5 µg/m3 increase: 1.17 (0.98, 1.40)), and were robust to co-pollutant adjustment. Elevated odds were observed for SO2 at lag day 0, and reduced odds for O3 at lag day 0; however, these associations were somewhat attenuated toward the null (SO2) or were not robust (O3) to co-pollutant adjustment. This analysis in a racially and socioeconomically diverse cohort, with a more inclusive definition of sudden unexpected death than is typically employed offers evidence that PM2.5 may be a clinically relevant trigger of sudden unexpected deaths in susceptible individuals.