Do Exposures to Green Space Reduce the Risk of Hypertension?


 Background: Few epidemiological research examined the effects of greenness on cardiovascular diseases in developing countries. We aimed to explore the relationships between green space and hypertension and blood pressure in China.Methods: This cross-sectional study recruited 39, 259 adults from five counties in central China. Blood pressure measurements were performed according to a standardized protocol. Normalized diﬀerence vegetation index (NDVI) and enhanced vegetation index (EVI) was used to assess the exposure to greenness. We used mixed linear models to test greenspace-cardiovascular disease outcome pathways.Results: Higher green space was related to decreased hypertension prevalence and blood pressure. After fully adjusting the covariates, each interquartile range increase in NDVI500m and EVI500m were related to an 8% decrease in odds of hypertension. The changes in SBP and DBP (95% CI) were - 0.88 mm Hg (- 1.17, - 0.58) and - 0.64 mm Hg (- 0.82, - 0.46) for NDVI, and - 0.79 mm Hg (- 1.14, - 0.45) and - 0.67 mm Hg (- 0.87, - 0.46) for EVI, respectively. Subgroup analyses showed that the effects of green space were more pronounced in males, smokers, and drinkers.Conclusions: The effects of green space may reduce the risk of hypertension. Also, behavioral factors may affect this potential pathway.


Introduction
Hypertension is the major cause of cardiovascular disease [1]. In China, hypertension prevalence was 23.2% and hypertension standardized treatment rate (aged 35 to 75 years) was only 22.9%, re ecting inadequate control of hypertension [2,3]. From the perspective of public health, community-level behavioral interventions with hypertension control are more effective than individual-level interventions [4]. Thus, exploration of the associations of possible population interventions with hypertension in China is crucial for national public health policy.
Residing in green space with a high level of air quality potentially leads to increasing frequency of physical activity and decreasing level of stress, which can further improve cardiovascular outcomes [5,6]. Growing epidemiological studies investigated the relationships between green space and blood pressure in recent years. EM Bijnens, TS Nawrot, RJ Loos, M Gielen, R Vlietinck, C Derom and MP Zeegers [7] indicated that higher greenspace was related to lower night SBP. Similarly, X Xiao, BY Yang, LW Hu, I Markevych, MS Bloom, SC Dharmage, B Jalaludin, LD Knibbs, J Heinrich, L Morawska, et al. [8] concluded that higher green space was related to lower hypertension prevalence. However, there have also been inconsistent ndings showing no signi cant association of greenness with hypertension [9][10][11]. More disadvantaged populations are already at greater risk of hypertension, thus investigating the relationships between green space and blood pressure is a pressing need for possible interventions. A study of 249, 405 participants in the United States observed negative associations of green space with hypertension in lower-income neighborhoods (OR = 0.86, 95% CI: 0.83, 0.89) but positive associations in higher-income neighborhoods (OR = 1.05, 95% CI: 1.02, 1.08) [12]. However, epidemiological research examing the relationships between green space and blood pressure remained limited in developing countries [13,14].
This study aimed to examine greenspace-cardiovascular disease outcome pathways and effect modi ers in the relationships.

Study population
Our study included the participants from the Rural Cohort Study in China (ChiCTR-OOC-15006699). We have published a detailed pro le elsewhere [15]. Brie y, this study recruited participants using multi-stage random cluster sampling (The owchart of participant recruitment was shown in Fig. 1). All participants lived in ve rural counties (Xinxiang, Suiping, Yuzhou, Yima, and Tongxu) in central China (Fig. 2). Overall, we obtained baseline survey data of 39, 259 participants. 165 participants were excluded due to missing the outcome variables. Finally, we included 39,094 participants in the analyses. Before the survey and physical examination, the study population has signed informed consent forms. The study was approved by the Ethics Committee of Zhengzhou University. The study was reported according to the guideline (The checklist of guidelines was shown in Table S1).

Outcome variables
We used electronic sphygmomanometers to measure blood pressure and calibrated it before each measurement according to a standardized protocol [16]. After participants rest for ve minutes, we conducted blood pressure measurements. Before the physical examination, smoking, drinking, and engaging in physical activity were not allowed for at least half an hour. Talking was not allowed during the blood pressure measurement. The study population was diagnosed with hypertension if they had taken antihypertensive medicine or they had been diagnosed with hypertension by a professional clinician or SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg [17].

Greenness exposure assessment
Individual exposure to green space was estimated using NDVI and EVI. NDVI was widely used for historical and climate applications [18] and EVI could minimize canopy-soil variations and improved sensitivity over dense vegetation conditions [19,20]. Therefore, the two vegetation indices could effectively characterize vegetation states and processes, which have been frequently used worldwide. We downloaded the vegetation index database of MODIS (MOD13A1). They were calculated from re ectance in red, near-infrared, and blue wavebands. High densities of green space showed higher vegetation index values [21]. The three-year average NDVI and EVI (500-m buffer) were used in the main analyses.

Air pollution assessment
Individual exposure to particulate matter with aerodynamic diameter ≤ 2.5 µm (PM 2.5 ) was estimated using the spatiotemporal models at a 0.1° × 0.1° spatial resolution. We had described the model elsewhere [22]. Brie y, we obtained air pollutant monitoring station data from the China Meteorological Administration. MODIS Collection 6 provided aerosol optical depth data. The spatiotemporal models showed high predictive accuracy and the 10-fold cross-validation R 2 for annual PM 2.5 was 86% [23].
Health status covariates included family history of hypertension.

Statistical analysis
The mixed linear models were employed to investigate the relationships between green space and hypertension and blood pressure. Model one was not adjusted for covariates. Model two was adjusted for demographic, socioeconomic, behavioral, and health status factors, and body mass index. Based on Model two, Model three additionally adjusted for PM 2.5 . Survey sites were adjusted as a random effect in the three models [26]. To test potential modi cations in the associations, we performed interaction analyses. If the P-value for interaction term < 0.05, the effect modi cations were considered to be statistically signi cant.
Several sensitivity analyses were conducted: (1) We explored the associations of green space with hypertension and blood pressure (1000-m buffer). (2) To examine individual exposure to green space, we investigated the relationships using NDVI 500m for different years. (3) The people who had taken antihypertensive medicines and all hypertensive patients were excluded to eliminate the causal effect of hypertension on blood pressure. All the analyses were performed using R 4.0.2.

Results
This study included 39, 094 participants and 60.6% (n = 23, 677) were females (Table 1). Table S2 showed detailed information in ve counties. Among 39, 094 participants, 19.1% (n = 7458) were smokers, 18.0% (n = 7053) were drinkers, 19.1% (n = 7461) had a high-fat diet, and 32.3% (n = 12, 614) reported a low level of physical activity. The three-year average NDVI and EVI (500-buffer) were 0.48 and 0.34 units, respectively ( Table 2). The distributions of vegetation indices strati ed by region were shown in Table S3. Among the 12, 763 hypertensive patients, 61.3% of them were self-reported, 38.7% were diagnosed by physicians. The prevalence of hypertension was 32.6% and 6, 267 patients had taken antihypertensive drugs within two weeks before the survey.  Table 3 showed the relationships between green space and hypertension and blood pressure. In model one, each 0.08 units increment in NDVI was related to an 11% decrease in odds of hypertension, and a decrease of 1.18 and 1.08 mmHg in SBP and DBP, respectively. In model three, each 0.08 units increase in NDVI was related to an 8% decrease in odds of hypertension, and reductions in SBP of 0.88 and DBP of 0.64 mmHg, respectively. We then conducted the subgroup analyses to examine the interaction effects of potential modi ers (Fig. 3). Table S4 and Table S5 showed detailed information. The effects of green space were more pronounced in males, smokers, and drinkers (P interaction < 0.05). For instance, each interquartile range (IQR) increment in NDVI was related to a 13% decrease in odds of hypertension in males, whereas 5% in females (P interaction = 0.005), and it was also associated with a reduction of 1.30 mmHg in SBP in males, whereas 0.63 mmHg in females (P interaction = 0.002). Besides, no signi cant effect modi cation was found in covariates including high-fat diet, physical activity, and Body mass index.
In sensitivity analyses, using the NDVI and EVI (1000-m buffer) showed similar results (Table S6), and using NDVI 500m values from different years was generally consistent with using the values of three-year average (Table S7). Changes in SBP and DBP remained similar when we excluded the people who had taken anti-hypertensive medicines (Table S8). After excluding all hypertensive patients, the relationships between green space and blood pressure were attenuated but remained signi cant, with an IQR (0.09 units) increase in NDVI 500m related to 0.40 and 0.32 mmHg decrease in SBP and DBP, respectively.

Discussion
It was one of few studies exploring the relationships between green space and hypertension and blood pressure in developing countries. The effects of green space may reduce the risk of hypertension. Besides, sex, smoking, and drinking could further modify the associations. The studies of associations between green space and blood pressure are still in the initial stage and lack of systematic studies in developing countries. Given increasing environmental pollution accompanied by the accelerated urbanization process and high prevalence of hypertension in China as well as other developing countries, our ndings may be particularly important for public health.
Some studies reported similar results [6,8,13,[27][28][29][30]. Our study showed that an IQR (0.08 units) increment in NDVI 500m was signi cantly associated with an 8% decrease in odds of hypertension. A study conducted in the urban area of the United States including 249, 405 indicated that a 0.1-units increase in NDVI 1000m was related to a 7% decrease in odds of hypertension [12]. Additionally, AM Dzhambov, I Markevych and P Lercher [18] reported that each IQR (0.16 units) increase in NDVI 500m was related to a 36% decrease in odds of hypertension based on a study of 555 adults in an Alpine valley of Austria. However, some studies showed inconsistent ndings. A study including 3,063 women in Germany reported null associations [11]. A meta-analysis of 4 studies reported no signi cant association of greenness with hypertension incidence [31]. Differences in characteristics of participants, study setting, greenness exposure assessment, statistical models, and adjustment for covariates may explain the inconsistency.
We found that higher green space was related to lower blood pressure. Our ndings were in line with a cross-sectional study of 3,150 in India [14] showing an interquartile range increase in NDVI 250m related to a decrease in SBP of 4.3 mmHg and a decrease in DBP of 1.2 mmHg, respectively. However, several previous studies showed inconsistent results [7,8,18,21]. BY Yang, I Markevych, MS Bloom, J Heinrich, Y Guo, L Morawska, SC Dharmage, LD Knibbs, B Jalaludin, P Jalava, et al. [27] reported that higher green space was related to lower SBP, whereas a null association was found between NDVI 500m and DBP. A study including 427 newborns in Belgium reported that an IQR (20.3%) increment in green space (5000 m buffer) was related to decrease in DBP of 1.2 mm Hg (95% CI: − 2.4, − 0.0), whereas no association was found for SBP (− 1.2 mm Hg, 95% CI: − 2.5, 0.1) [32]. LD Bloemsma, U Gehring, JO Klompmaker, G Hoek, NAH Janssen, E Lebret, B Brunekreef and AH Wijga [10] conducted a study of 1,505 children, which found that green space was not signi cantly related to changes in blood pressure. The study participants listed above (e.g., adults, newborns, and children) have different characteristics, lifestyles, living, and working environments that may modify the effects of greenness. Thus, the relationships between green space and blood pressure remained unclear.
Residing in green space may improve cardiovascular disease outcomes [6]. The mechanisms underlying the association may be explained by immunological and psychological pathways [6,33,34]. Speci cally, people residing in green space are exposed to more diverse microbes bene cial to the host immune system (improving immune regulation) and less noise and air pollution (reducing in ammatory response), are more likely to increase physical activity (strengthening immune and nervous system), promote the exchange of microbiota (increase social interactions), and promote metabolism (sunlight helps in the synthesis of vitamin D) [33]. Higher green space may bene t mental health such as depression [35,36].
The subgroup analyses indicated that the effects of green space were more pronounced in males, smokers, and drinkers. Knibbs, B Jalaludin, P Jalava, et al. [27] reported that 0.17 units increase in NDVI 500m was related to lower hypertension prevalence for females, whereas a null association was found for males. Inconsistent results may due to them that women have a higher frequency of using green space in China, for example, square dancing was the most popular exercise among them [27]. AM Dzhambov, I Markevych and P Lercher [18] concluded that there was no evidence of signi cant interactions between sex and greennesshypertension pathway. There has been limited evidence of how behavioral factors affect the relationships between green space and hypertension and blood pressure. Existing evidence showed that green space could provide diverse microbes, some of which are important inducers of the immunoregulatory pathways, and activation of the immune regulatory system consequently reduced chronic in ammation [33]. C Menni, C Lin, M Cecelja, M Mangino, ML Matey-Hernandez, L Keehn, RP Mohney, CJ Steves, TD Spector, C-F Kuo, et al. [37] indicated the signi cant relationships between gut microbial diversity and lower arterial stiffness. Smoking and drinking could trigger in ammatory response, oxidative stress, and metabolic disorders, which further affect systemic vascular resistance [38,39]. Thus, the effects of green space on in ammatory response and immune system could be more pronounced in smokers and drinkers than normal people.
Several limitations existed in this study. First, as an inherent drawback of cross-sectional design, causal associations should be treated with caution. Second, demographic covariates, socioeconomic covariates, and health behavior covariates were collected using the questionnaire, which may introduce recall bias. Third, some potential confounders including tra c noise, the walkability of a community, psychological status, and indoor greenness exposure were not adjusted in the model because of data unavailability [8,18].

Conclusion
Page 10/14 In summary, our study suggested that the effects of green space may reduce the risk of hypertension. Furthermore, the effects of greenness were more pronounced in males, smokers, and drinkers. Given the limitations of the cross-sectional study, prospective studies are warranted in the future.