large image size. We also recommend the use of MODIS-NDVI with the best spatial resolution 7
of 250 x 250 m2 for local studies or studies with smaller scopes (e.g. city scale).
8
Some limitations of the study should be noted. Knowing that this study was conducted with 9
an ecological study design, the measure of exposure and outcome variables were only a proxy-10
based on the country-level average. Used country-level databases might not best proportion for 11
variable assessment and could impact on the modifiable areal unit problem as a source of 12
statistical bias. However, due to the lack of residential neighborhood greenness and tree species 13
database for each country, the effects of neighborhood greenspace and biodiversity in the 14
developed models cannot take into account. We also recognized the lack of individual health 15
information might have some impacts on the strength of evidence provided by the results. The 16
causality remains to be explored even though a negative statistical association was found 17
between greenness exposure and the burden of cardiovascular diseases in terms of IHD and 18
stroke. Nevertheless, given we have considered several potential risk factors to adjust the 19
models and identified the robustness estimations, this study could serve an essential role in a 20
better knowledge of how exposure to greenness can be linked to the burden of cardiovascular 21
diseases in terms of IHD and stroke globally. Furthermore, the study findings also openly 22
provide a substantial possibility for further study in the understanding of alleviating human 23
health burdens. Furthermore, we found a negative mediation effect of obesity on the association 24
between greenness and ischemic heart diseases. However, the interpretation of this finding 25
should be cautious since several factors contributing to obesity (e.g. dietary, physical activity) 26
were not controlled that may lead to confounding bias on the obesity-IHD association. This 27
limitation may also explain the unexpected positive mediation role of obesity on the 28
relationship between greenness and stroke that can be discussed in subsequent studies.
29
Otherwise, some covariates have not been adjusted in the model due to the lack of global 30
datasets, such as genetic or hereditary disease, ethnic/race, and other covariates those may 31
influence cardiovascular diseases. Related to exposures, we did not consider meteorological 32
factors such as temperature and precipitation. We suggest future studies consider these 33
meteorological factors since several studies have recognized their association with 34
cardiovascular diseases. Finally, this study focused on a global analysis with a country as the 35
basic unit in the statistical analysis. Knowing that the DALY data provided by WHO is only 36
available at the country-level, not available at the states and/or provinces-cities scale. A 37
separate analysis for big countries such as the USA, Canada, and China for considering the 38
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21
within-country variability cannot be done in our study. Future studies could focus on the effects 1
of greenness benefits at local communities in the case a finer-resolution DALY data becomes 2
available.
3
Cardiovascular disease is the leading cause of death in the human population, and 80% of 4
its deaths occur in low and middle-income countries (GBD 2017 Cause of Death of 5
Collaborators, 2018; WHO, 2019). WHO noted that the total economic losses due to 6
cardiovascular diseases were estimated to reach $ 3.7 trillion between 2011 and 2015, 7
representing approximately half of the economic burden for treating non-communicable 8
diseases, and 2% of Gross Domestic Product across countries (Bloom, et al., 2013). As the 9
main emphasis, this study confirmed that greenness can reduce the health burden due to 10
cardiovascular diseases significantly. Knowing that exposure to greenness is one of the natural 11
features that could be freely accessed, our findings related to the health benefits of green spaces 12
could provide scientific evidences for policymakers and communities in minimizing the health 13
burden not only from physical or psychological aspects, but also economic burden through 14
suppressing the costs spent for medical treatment due to cardiovascular diseases.
15
5. Conclusion 16
This study is the first global-scale study with an ecological study design to assess the 17
association between greenness and cardiovascular diseases based on the data from 183 18
countries worldwide. Our results showed a consistently significant negative relationship 19
between greenness and the burden of cardiovascular diseases, including both IHD and stroke.
20
The stratified analysis showed that greenness could provide health benefits regardless of gender 21
differences and age groups. Greenness exposure was also confirmed to have a significant effect 22
in low and middle-income countries, especially for IHD burden. Despite the limitations noted, 23
our study contributed to a global research baseline that could be used as a reference for 24
environmental development and public health. We suggest policymakers and communities to 25
green environment management in order to reduce the global health burden.
26 3
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22
Author Contributions: Conceptualization, C.D.W., J.D.S., A.KA., and H.J.S.; methodology, C.D.W., A.K.A., 1
and W.C.P.; formal analysis, A.K.A., and W.C.P.; writing—original draft preparation, C.D.W, and A.K.A..;
2
writing—review and editing, C.D.W., A.K.A., Y.L.G., S.C.C.L., C.P.Y., W.C.P., J.D.S., and H.J.S.; visualization, 3
A.K.A..; supervision, C.D.W., S.C.C.L., and H.J.S.; funding acquisition, C.D.W., H.J.S., S.C.C.L., and J.D.S.
4
Funding: This study was funded by the Ministry of Science and Technology, R.O.C. (MOST 107-2314-B-010-5
059-MY3).
6
Data Availability: The data that support the findings of this study are openly available at the following URL/DOI.
7
• Land Processes Distributed Active Archive Center - NASA: https://lpdaac.usgs.gov/
8
• Global Health Estimates - WHO: http://www.who.int/healthinfo/global_burden_disease/en/
9
• World Population Prospects - United Nations: https://esa.un.org/unpd/wpp/
10
• World Bank list of economies – World Bank group:
11
https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-12
groups 13
• The Atmosphere Composition Analysis Group - Prof. Randall Martin from Dalhousie University:
14
http://fizz.phys.dal.ca/~atmos/martin/?page_id=140 15
Acknowledgments: This study was funded by the Ministry of Science and Technology, R.O.C. This study was 16
supported by the World Health Organization (WHO), who provided the metrics, i.e. disability-adjusted life years 17
(DALY) database to estimate global health burden of IHD and stroke; the National Aeronautics and Space 18
Administration (NASA), which provided global greenness - NDVI data (MOD13A3); the Atmospheric 19
Composition Analysis Group, which provided global PM2.5 data; the United Nations Agency, which served 20
demographic data; and the World Bank Group, which provided the provisions of economic status, the prevalence 21
rate of smoking, alcohol consumption and risk factor data at a country-level.
22
Conflicts of Interest: The authors declare no conflict of interests. The funders had no role in the design of the 23
study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to 24
publish the results 25
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