Fine particulate matter-sudden death association modified by ventricular hypertrophy and inflammation: a case-crossover study.

Background: Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Methods: Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 µg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Results: Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. Conclusion: LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.

Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.

Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (n = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact P-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, P-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, P = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the P-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, P-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.

Climate Change and Cardiovascular Health: A Systematic Review.

Importance: Climate change may increase the risk of adverse cardiovascular outcomes by causing direct physiologic changes, psychological distress, and disruption of health-related infrastructure. Yet, the association between numerous climate change-related environmental stressors and the incidence of adverse cardiovascular events has not been systematically reviewed. Objective: To review the current evidence on the association between climate change-related environmental stressors and adverse cardiovascular outcomes. Evidence Review: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify peer-reviewed publications from January 1, 1970, through November 15, 2023, that evaluated associations between environmental exposures and cardiovascular mortality, acute cardiovascular events, and related health care utilization. Studies that examined only nonwildfire-sourced particulate air pollution were excluded. Two investigators independently screened 20 798 articles and selected 2564 for full-text review. Study quality was assessed using the Navigation Guide framework. Findings were qualitatively synthesized as substantial differences in study design precluded quantitative meta-analysis. Findings: Of 492 observational studies that met inclusion criteria, 182 examined extreme temperature, 210 ground-level ozone, 45 wildfire smoke, and 63 extreme weather events, such as hurricanes, dust storms, and droughts. These studies presented findings from 30 high-income countries, 17 middle-income countries, and 1 low-income country. The strength of evidence was rated as sufficient for extreme temperature; ground-level ozone; tropical storms, hurricanes, and cyclones; and dust storms. Evidence was limited for wildfire smoke and inadequate for drought and mudslides. Exposure to extreme temperature was associated with increased cardiovascular mortality and morbidity, but the magnitude varied with temperature and duration of exposure. Ground-level ozone amplified the risk associated with higher temperatures and vice versa. Extreme weather events, such as hurricanes, were associated with increased cardiovascular risk that persisted for many months after the initial event. Some studies noted a small increase in cardiovascular mortality, out-of-hospital cardiac arrests, and hospitalizations for ischemic heart disease after exposure to wildfire smoke, while others found no association. Older adults, racial and ethnic minoritized populations, and lower-wealth communities were disproportionately affected. Conclusions and Relevance: Several environmental stressors that are predicted to increase in frequency and intensity with climate change are associated with increased cardiovascular risk, but data on outcomes in low-income countries are lacking. Urgent action is needed to mitigate climate change-associated cardiovascular risk, particularly in vulnerable populations.

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.