Ambient Air Pollutants and Risk of Fatal Coronary Heart Disease Among Kidney Transplant Recipients

doi:10.1053/j.ajkd.2011.05.017

American Journal of Kidney Diseases

Volume 58, Issue 4, October 2011, Pages 608-616

https://doi.org/10.1053/j.ajkd.2011.05.017 Get rights and content

Background

There is increasing evidence that specific ambient air pollutants are associated with coronary heart disease (CHD) morbidity and mortality. Because kidney transplant recipients have prevalent traditional and nontraditional risk factors, they may constitute a sensitive subgroup.

Study Design

Retrospective cohort.

Setting & Participants

This study includes 32,239 nonsmoking adult kidney transplant recipients who underwent transplant in 1997-2003, identified through the US Renal Data System and living in the United States within 50 km of an air pollution monitoring station.

Predictor

Long-term ambient pollutant ozone and particulate matter ≤10 μm (PM₁₀), assessed from monthly concentrations of ozone and PM₁₀ calculated from ambient monitoring data by the US Environmental Protection Agency Air Quality System and interpolated to zip code centroids according to patients' residence.

Outcomes

Outcomes of interest were death from CHD and natural-cause mortality.

Results

For the entire transplant cohort, average pollutant levels for ozone and PM₁₀ were 25.5 ± 4.4 parts per billion (ppb) and 25.3 ± 6.4 μg/m³, respectively. Correlation between ozone and PM₁₀ values was low, but statistically significant (P < 0.001). There were deaths from CHD (n = 267) and natural causes (n = 2,076) during the 7-year study period. For each 10-ppb increase in ozone, the risk of fatal CHD increased by 35% (RR, 1.35; 95% CI, 1.04-1.77) in the single-pollutant model and 34% (RR, 1.34; 95% CI, 1.03-1.76) in the 2-pollutant model. No independent association was found between CHD and PM₁₀. No significant association was identified for PM₁₀ or ozone level and natural-cause mortality (RR, 1.09; 95% CI, 0.99-1.21).

Limitations

Exposure assignment based on only residential location.

Conclusions

For kidney transplant recipients, ambient ozone levels potentially are associated with higher risk of fatal CHD. These findings may have implications for regulations governing air pollution and the development of individual CHD risk-reduction strategies.

Section snippets

Study Population

Study participants were identified through the US Renal Data System (USRDS), a national data repository containing extensive demographic (including updated residential information), diagnostic, hospital information, and mortality data for persons living with end-stage renal disease (ESRD). Our study population included first-time kidney transplant recipients 18 years and older who underwent transplant in 1997-2003, with at least 1 year of transplant survival, residing within 50 km of an air

Study Population

The transplant population for this study consisted of individuals from across the entire continental United States (Fig 1). A total of 267 CHD deaths and 2,076 natural-cause deaths occurred in the 32,239 individuals studied (230.2 CHD deaths/100,000 person-years) during the 7-year study period. A combined total of 115,983.5 person-years was contributed by cohort participants during the follow-up period. Deaths from CHD accounted for 12.9% of the total 2,076 natural-cause deaths. For those with

Discussion

To our knowledge, no other study has assessed the impact of ambient air pollution on organ transplant recipients. Findings from this cohort study provide support for the hypothesis that air pollution exacerbates the atherosclerotic process and increases the risk of fatal CHD in kidney transplant recipients. Most studies of the effect of ambient air pollution on risk of CHD have found a clear and harmful effect of particulate matter, especially PM_2.5 (particulate matter ≤2.5 μm), but usually

Acknowledgements

The authors thank Rebekah Spencer, DMD (Oregon Health and Science University), for valuable comments with drafting of the manuscript.

The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.

Support: This study was in part funded by Environmental Protection Agency grant CR–83054701–0.

Financial Disclosure: The authors declare

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Cited by (29)

Long-term exposure to ambient ozone and mortality in a population-based cohort of South Korea: Considering for an alternative exposure time metric
2022, Environmental Pollution
Citation Excerpt :
After full-text examination of the 45 (41 from the previous reviews and 4 from the databases) identified studies, we excluded seven that did not use the Cox proportional hazards model to estimate the association between ozone and mortality (Hao et al., 2015; Kazemiparkouhi et al., 2020; Li et al., 2016; Raaschou-Nielsen et al., 2020; Rush et al., 2017; Wei et al., 2020; Yazdi et al., 2021); a study that did not report the exposure assessment method for ozone (Tseng et al., 2015); five that did not use 24-h mean or 8-h maximum ozone for the exposure metrics (Health Effects Institute, 2000; Krewski et al., 2009; Jerrett et al., 2009; Lipfert et al., 2006b; Smith et al., 2009); and one that reported HRs only in graphical format (Thomson et al., 2020). Finally, 31 previous studies (29 for all-cause mortality, 17 for circulatory mortality, and 17 for respiratory mortality, Table S1) (Abbey et al., 1999; Bauwelinck et al., 2022; Bentayeb et al., 2015; Cakmak et al., 2018; Cakmak et al., 2016; Carey et al., 2013; Crouse et al., 2015; Desikan et al., 2016; Di et al., 2017; Eckel et al., 2016; Hvidtfeldt et al., 2019; Jerrett et al., 2013; Kim et al., 2017; Lim et al., 2019; Lipfert et al., 2006a; Lipsett et al., 2011; Malik et al., 2019; Niu et al., 2022; Paul et al., 2020; Sese et al., 2018; Shi et al., 2022; So et al., 2022; Sommar et al., 2021; Spencer-Hwang et al., 2011; Stafoggia et al., 2022; Strak et al., 2021; Tonne et al., 2016; Turner et al., 2016; Weichenthal et al., 2017; Xu et al., 2013; Zanobetti and Schwartz, 2011) and the present study were included in the meta-analysis. Estimated HRs and 95% confidence intervals (CIs) were extracted from each study and standardized to a 10 ppb increase in ozone.
Studies on the health effects of long-term ozone exposure remain limited with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone and mortality in South Korea, using different exposure metrics. We also examined whether heterogeneity between previous studies was due to the different exposure metrics. The study population comprised 179,806 participants from the National Health Insurance Service-National Sample Cohort (2002–2015) residing in seven major cities in South Korea. Several ozone exposure metrics (year-round 24-h, year-round 8-h, warm-season 24-h, and warm-season 8-h) were calculated. Time-varying Cox proportional hazards models were used to estimate the association between ozone and all-cause and cause-specific mortalities. Random-effect meta-analysis and meta-regression analysis were performed to pool the effect estimates of previous studies and examine whether the exposure metric can explain the between-study heterogeneity. The hazard ratios (HRs) per 10 ppb increment in year-round 24-h ozone for all-cause (HR, 1.18; 95% CI, 1.07–1.29) and circulatory (HR, 1.52; 95% CI, 1.25–1.84) mortality were higher than those of the other metrics. Year-round 8-h ozone exhibited the largest association with respiratory mortality (HR, 1.43; 95% CI, 1.04–1.96). A meta-analysis of 29 previous studies and the present study showed the largest HR for all-cause mortality from studies using year-round 8-h exposure (HR, 1.014; 95% CI, 0.994–1.033). The exposure metric was significantly associated with effect estimates in the multivariable meta-regression model. In conclusion, in the population-based cohort in South Korea, we found positive associations between several long-term ozone exposure metrics and mortality. The different ozone exposure metrics exhibited heterogeneous effect estimates. A year-round 24-h average ozone metric also could be considered an alternative long-term standard for ozone.
Ambient air pollution and posttransplant outcomes among kidney transplant recipients
2021, American Journal of Transplantation
Fine particulate matter (PM_2.5), a common form of air pollution which can induce systemic inflammatory response, is a risk factor for adverse health outcomes. Kidney transplant (KT) recipients are likely vulnerable to PM_2.5 due to comorbidity and chronic immunosuppression. We sought to quantify the association between PM_2.5 and post-KT outcomes. For adult KT recipients (1/1/2010–12/31/2016) in the Scientific Registry of Transplant Recipients, we estimated annual zip-code level PM_2.5 concentrations at the time of KT using NASA’s SEDAC Global PM_2.5 Grids. We determined the associations between PM_2.5 and delayed graft function (DGF) and 1-year acute rejection using logistic regression and death-censored graft failure (DCGF) and mortality using Cox proportional hazard models. All models were adjusted for sociodemographics, recipient, transplant, and ZIP code level confounders. Among 87 233 KT recipients, PM_2.5 was associated with increased odds of DGF (OR = 1.59; 95% CI: 1.48–1.71) and 1-year acute rejection (OR = 1.31; 95% CI: 1.17–1.46) and increased risk of all-cause mortality (HR = 1.15; 95% CI: 1.07–1.23) but not DCGF (HR = 1.05; 95% CI: 0.97–1.51). In conclusion, PM_2.5 was associated with higher odds of DGF and 1-year acute rejection and elevated risk of mortality among KT recipients. Our study highlights the importance of considering environmental exposure as risk factors for post-KT outcomes.
Long-term exposure to PM and all-cause and cause-specific mortality: A systematic review and meta-analysis
2020, Environment International
As new scientific evidence on health effects of air pollution is generated, air quality guidelines need to be periodically updated. The objective of this review is to support the derivation of updated guidelines by the World Health Organization (WHO) by performing a systematic review of evidence of associations between long-term exposure to particulate matter with diameter under 2.5 µm (PM_2.5) and particulate matter with diameter under 10 µm (PM₁₀), in relation to all-cause and cause-specific mortality. As there is especially uncertainty about the relationship at the low and high end of the exposure range, the review needed to provide an indication of the shape of the concentration–response function (CRF).
We systematically searched MEDLINE and EMBASE from database inception to 9 October 2018. Articles were checked for eligibility by two reviewers. We included cohort and case-control studies on outdoor air pollution in human populations using individual level data. In addition to natural-cause mortality, we evaluated mortality from circulatory diseases (ischemic heart disease (IHD) and cerebrovascular disease (stroke) also specifically), respiratory diseases (Chronic Obstructive Pulmonary Disease (COPD) and acute lower respiratory infection (ALRI) also specifically) and lung cancer. A random-effect meta-analysis was performed when at least three studies were available for a specific exposure-outcome pair. Risk of bias was assessed for all included articles using a specifically developed tool coordinated by WHO. Additional analyses were performed to assess consistency across geographic region, explain heterogeneity and explore the shape of the CRF. An adapted GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment of the body of evidence was made using a specifically developed tool coordinated by WHO.
A large number (N = 107) of predominantly cohort studies (N = 104) were included after screening more than 3000 abstracts. Studies were conducted globally with the majority of studies from North America (N = 62) and Europe (N = 25). More studies used PM_2.5 (N = 71) as the exposure metric than PM₁₀ (N = 42). PM_2.5 was significantly associated with all causes of death evaluated. The combined Risk Ratio (RR) for PM_2.5 and natural-cause mortality was 1.08 (95%CI 1.06, 1.09) per 10 µg/m³. Meta analyses of studies conducted at the low mean PM_2.5 levels (<25, 20, 15, 12, 10 µg/m³) yielded RRs that were similar or higher compared to the overall RR, consistent with the finding of generally linear or supra-linear CRFs in individual studies. Pooled RRs were almost identical for studies conducted in North America, Europe and Western Pacific region. PM₁₀ was significantly associated with natural-cause and most but not all causes of death. Application of the risk of bias tool showed that few studies were at a high risk of bias in any domain. Application of the adapted GRADE tool resulted in an assessment of “high certainty of evidence” for PM_2.5 with all assessed endpoints except for respiratory mortality (moderate). The evidence was rated as less certain for PM₁₀ and cause-specific mortality (“moderate” for circulatory, IHD, COPD and “low” for stroke mortality.
Compared to the previous global WHO evaluation, the evidence base has increased substantially. However, studies conducted in low- and middle- income countries (LMICs) are still limited. There is clear evidence that both PM_2.5 and PM₁₀ were associated with increased mortality from all causes, cardiovascular disease, respiratory disease and lung cancer. Associations remained below the current WHO guideline exposure level of 10 µg/m³ for PM_2.5.
Systematic review registration number (PROSPERO ID): CRD42018082577.
Ambient Air Pollution and Mortality After Cardiac Transplantation
2019, Journal of the American College of Cardiology
Citation Excerpt :
Studies of the association between air pollution and outcomes in solid organ transplant recipients are scarce. In 1 study of 32,239 nonsmoking adult kidney transplant recipients between 1997 and 2003, each 10 parts/billion increment in ozone levels was associated with a 35% increase in deaths from coronary artery disease (25). In a study of 5,707 patients who underwent lung transplantation in 10 European countries, each 6 μg/m3 increment in PM10 was associated with an 8% increase in mortality among the macrolide-free group (HR: 1.08; 95% CI: 1.00 to 1.17; p = 0.049) (26).
Heart transplant recipients are at high risk for mortality, with traditional risk scores performing modestly in predicting post-transplant survival, underscoring the importance of as yet unidentified factors in determining prognosis. In this analysis, the association between PM_2.5 exposure levels and survival after heart transplantation were investigated.
This study sought to study the association between PM_2.5 exposure and mortality following heart transplantation.
On the basis of the zip code of residence, mortality data in patients who underwent heart transplantation (2004 to 2015) in the United Network for Organ Sharing (UNOS) database were linked with validated estimates of fine particulate matter concentrations (particles with diameter <2.5 μm [PM_2.5]; 1 × 1-km grids) for each calendar year during which a UNOS cardiac transplant recipient was at risk for death. Cox proportional hazard models were used to estimate the relationship between exposure and overall mortality adjusting for recipient, donor, and neighborhood variables.
A total of 21,800 patients with 86,713 patient-years of follow-up was included. Mean age at transplantation was 52.6 ± 12.6 years, 75% were male, 69% were white, and 39% had ischemic etiology of heart failure. Mean annual exposure to PM_2.5 was 10.6 ± 2.3 μg/m³. At a median follow-up of 4.8 (95% confidence interval: 2.0 to 7.8) years, 5,208 patients (23.9%) had died. The estimated mortality hazard ratio, per 10 μg/m³ increment increase in annual PM_2.5 exposure was 1.43 (95% confidence interval: 1.21 to 1.49). After adjusting for 30 recipient, donor, and neighborhood variables, the estimated mortality hazard ratio per 10 μg/m³ increment in annual exposure to PM_2.5 was 1.26 (95% confidence interval: 1.11 to 1.43) relative increase in hazard of mortality. This association was consistent across subgroups.
This study provides evidence linking air pollution with mortality after heart transplantation. These results suggest an important influence of a key environmental factor in outcomes following heart transplantation, and supports the need for further studies in this population.
Does Air Pollution Increase Risk of Mortality After Cardiac Transplantation?
2019, Journal of the American College of Cardiology
Traffic-related air pollution and solid organ transplant failure in Great Britain: A retrospective cohort study
2018, Journal of Transport and Health
Citation Excerpt :
It is argued that the transplanted lung is especially susceptible to the effects of air pollution because of its direct contact with the environment (Nawrot et al., 2011). In fact there appear to be no studies of this issue in other, solid-organ transplant patients, although an analysis of 32,000 recipients of kidney grafts in the United States related the risk of fatal coronary heart disease to ambient ozone levels (Spencer-Hwang et al., 2011). We designed a retrospective cohort study to examine if the findings above could be replicated in the United Kingdom; and in particular to study whether any effect in lung transplant patients was specific or could also be observed in recipients of other solid-organ grafts.
Limited evidence suggests that exposure to traffic related air pollution is associated with graft failure among lung transplant recipients. We explored associations between pollution and transplant failure among lung and other solid organ transplant recipients in Great Britain through a retrospective cohort study.
All patients who received a lung, heart, liver, or kidney transplant between 2000 and 2008 in Great Britain were included, as recorded in the National Health Service Blood and Transplant (NHSBT) register and followed to March 2015. Using residential addresses at time of transplant we calculated distance to nearest (major) road and modelled annual average exposures to airborne nitrogen oxides and particulate matter of diameter ≤10µm and ≤2.5µm for each transplant recipient. All-cause mortality or graft failure (kidney) during follow up was the main outcome; median follow-up was around 10 years for each organ type. We fitted Cox regression models with adjustment for age, sex, year of transplant and donor age/smoking status.
780 lung, 1213 heart, 3650 liver and 11966 graft kidney transplant patients were analysed. We did not find any consistent associations between mortality or graft failure and any of the analysed air pollutants or road metrics. Although, exposure to particulate matter was associated with renal transplant failure in univariable analyses but not after adjustment for confounders.
Our analysis does not confirm previously reported associations between traffic-related air pollution exposure and the risk of transplant failure.

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: Originally published online July 21, 2011.

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Original InvestigationTransplantationAmbient Air Pollutants and Risk of Fatal Coronary Heart Disease Among Kidney Transplant Recipients

Background

Study Design

Setting & Participants

Predictor

Outcomes

Results

Limitations

Conclusions

Section snippets

Study Population

Study Population

Discussion

Acknowledgements

Environ Res

Am J Kidney Dis

Transplant Proc

Toxicol Appl Pharmacol

Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases

JAMA

Air pollution and hospital admissions for ischemic heart diseases among individuals 64+ years of age residing in Seoul, Korea

Arch Environ Health

The effects of air pollution on hospitalizations for cardiovascular disease in elderly people in Australian and New Zealand cities

Environ Health Perspect

Relation between short-term fine-particulate matter exposure and onset of myocardial infarction

Epidemiology

Temperature, air pollution, and hospitalization for cardiovascular diseases among elderly people in Denver

Environ Health Perspect

Effects of particulate and gaseous air pollution on cardiorespiratory hospitalizations

Arch Environ Health

Ambient air pollution and atherosclerosis in Los Angeles

Environ Health Perspect

Outdoor air pollution, mortality, and hospital admissions from coronary heart disease in Sheffield, UK: a small-area level ecological study

Eur Heart J

The association between fatal coronary heart disease and ambient particulate air pollution: are females at greater risk?

Environ Health Perspect

The association of daily diabetes mortality and outdoor air pollution in Shanghai, China

J Environ Health

Are diabetics more susceptible to the health effects of airborne particles?

Am J Respir Crit Care Med

Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation

Environ Health Perspect

Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function

Circulation

Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency

Circulation

Original Investigation
Transplantation
Ambient Air Pollutants and Risk of Fatal Coronary Heart Disease Among Kidney Transplant Recipients