Long-term ozone exposure has been associated with cardiovascular disease (CVD) mortality in mounting cohort evidence, yet its relationship with incident CVD was poorly understood, especially in low- and middle-income countries (LMICs) experiencing high ambient air pollution. We carried out a nationwide perspective cohort study from 2010 through 2018 by dynamically enrolling 36985 participates across Chinese mainland. Warm-season (April–September) ozone concentrations were estimated using satellite-based machine-learning models with national coverage. Cox proportional hazards model with time-varying exposures was employed to evaluate the association of long-term ozone exposure with incident CVD (overall CVD, hypertension, stroke, and coronary heart disease [CHD]). Assuming causality, a counterfactual framework was employed to estimate ozone-attributable CVD burden based on the exposure-response (E-R) relationship obtained from this study. Decomposition analysis was utilized to quantify the contributions of four key direct driving factors (ozone exposure, population size, age structure, and incidence rate) to the net change of ozone-related CVD cases between 2010 and 2018. A total of 4428 CVD, 2600 hypertension, 1174 stroke, and 337 CHD events were reported during 9-year follow-up. Each 10-μg/m³ increase in warm-season ozone was associated with an incident risk of 1.078 (95% confidence interval [CI]:1.050–1.106) for overall CVD, 1.098 (95% CI:1.062–1.135) for hypertension, 1.073 (95% CI:1.019–1.131) for stroke, and 1.150 (95% CI: 1.038–1.274) for CHD, respectively. We observed no departure from linear E-R relationships of ozone exposure with overall CVD (Pnonlinear= 0.22), hypertension (Pnonlinear=0.19), stroke (Pnonlinear= 0.70), and CHD (Pnonlinear= 0.44) at a broad concentration range of 60–160 µg/m3. Compared with rural dwellers, those residing in urban areas were at significantly greater ozone-associated incident risks of overall CVD, hypertension, and stroke. We estimated 1.22 million (10.6% of overall CVD in 2018) incident CVD cases could be attributable to ambient ozone pollution in 2018, representing an overall 40.9% growth (0.36 million) compared to 2010 (0.87 million, 9.7% of overall CVD in 2010). This remarkable rise in ozone-attributable CVD cases was primary driven by population aging (+24.0%), followed by increase in ozone concentration (+10.5) and population size (+6.7%). Long-term ozone exposure was associated with an elevated risk and burden of incident CVD in Chinese adults, especially among urban dwellers. Our findings underscored policy priorities of implementing joint control measures for fine particulate matter and ozone in the context of accelerated urbanization and population aging in China. This study well depicted spatiotemporal patterns of O3-attributable CVD burden in Chinese mainland and quantify underlying driving factors, which would facilitate dynamic assessments of ozone-related health impacts and development of region-specific ozone policies in China. 

Long-Term Ambient Ozone Exposure and Incident Cardiovascular Diseases: National Cohort Evidence in China

Existing assessments might have underappreciated ozone-related health impacts worldwide. Here our study assesses current global ozone pollution using the high-resolution (0.05°) estimation from a geo-ensemble learning model, with key focuses on population exposure and all-cause mortality burden. Our model demonstrates strong performance, achieving a mean bias of less than -1.5 parts per billion against in-situ measurements. We estimate that 66.2% of the global population is exposed to excess ozone for short term (> 30 days per year), and 94.2% suffers from long-term exposure. Furthermore, severe ozone exposure levels are observed in Cropland areas, particularly over Asia. Importantly, the all-cause ozone-attributable deaths significantly surpass previous recognition from specific diseases worldwide. Notably, mid-latitude Asia (30°N) and the western United States show high mortality burden, contributing substantially to global ozone-attributable deaths. Our study highlights current significant global ozone-related health risks and may benefit the ozone-exposed population in the future. This study assesses current global ozone pollution and reveals significant O₃-related health risks, with key focuses on population exposure and all-cause mortality burden, using the high-resolution estimation from a geo-ensemble learning model. 

Substantially underestimated global health risks of current ozone pollution

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and –2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness and highlight the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the “three-child policy” in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health. 

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

An estimate of global cardiovascular mortality burden attributable to ambient ozone exposure reveals urban-rural environmental injustice

The Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) established a maternity cohort to investigate the relationship between perinatal abnormalities and various risk factors among the Chinese maternal population. The primary aim of ZEBRA is to explore the feasibility of early-stage risk prediction and the forecast of adverse perinatal symptoms and gestational outcomes. The cohort is ambidirectional, with a retrospective arm tracking 6,275 pregnant females enrolled between 2013 and 2016, and a prospective arm recruiting 112,414 participants since the baseline year of 2017. The current ZEBRA maternity cohort database comprises a diverse range of sociodemographic features, physiological characteristics, medical history, therapeutic interventions, and measurements of environmental exposures. Going forward, the cohort will continue to enrol a wider range of participants and collect an even more extensive array of features. ZEBRA is seeking collaborations with both national and international multi-cohort studies to contribute to the field of epidemiology, and provide valuable evidence-based insights for global maternal and child healthcare.

/pdf/cohort-profile-zhejiang-environmental-and-birth-health-2v0u0ths.pdf

Cohort Profile: Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) Maternity Cohort

Ever-increasing ambient ozone (O3) pollution in China has been exacerbating cardiopulmonary premature deaths. However, the urban-rural exposure inequity has seldom been explored. Here, we assess population-scale O3 exposure and mortality burdens between 1990 and 2019 based on integrated pollution tracking and epidemiological evidence. We find Chinese population have been suffering from climbing O3 exposure by 4.3 ± 2.8 ppb per decade as a result of rapid urbanization and growing prosperity of socioeconomic activities. Rural residents are broadly exposed to 9.8 ± 4.1 ppb higher ambient O3 than the adjacent urban citizens, and thus urbanization-oriented migration compromises the exposure-associated mortality on total population. Cardiopulmonary excess premature deaths attributable to long-term O3 exposure, 373,500 (95% uncertainty interval [UI]: 240,600-510,900) in 2019, is underestimated in previous studies due to ignorance of cardiovascular causes. Future O3 pollution policy should focus more on rural population who are facing an aggravating threat of mortality risks to ameliorate environmental health injustice. 

Antagonism between ambient ozone increasing and urbanization-oriented population migration on Chinese cardiopulmonary mortality

China’s unwavering determination in protecting pregnancy and perinatal health

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Antagonism between ambient ozone increasing and urbanization-oriented population migration on Chinese cardiopulmonary mortality

China’s unwavering determination in protecting pregnancy and perinatal health