Causal Relationship Between Air Pollutants and Blood Pressure Phenotypes: A Mendelian Randomization Study

Overview

Journal Glob Heart

Publisher Ubiquity Press

Specialty Cardiology & Vascular Diseases

Date 2025 Mar 3

PMID 40026346

Authors

Xianshang Zhu

Huabo Mao

Hongyu Zeng

Fengli Lv

Jiancheng Wang

Affiliations

Soon will be listed here.

Abstract

Objectives: Hypertension is a chronic disease widely prevalent around the world. While previous observational studies have suggested a link between air pollutants and an increased risk of hypertension, causality has not been established. Our study aimed to investigate potential causal relationships between five air pollutants and four blood pressure phenotypes through two-sample Mendelian randomization.

Methods: Two-sample Mendelian randomization (MR) analyses were performed using genome-wide association studies (GWAS) data from the IEU OpenGWAS project. The main analysis method was the inverse variance weighting (IVW) method. Heterogeneity was assessed by Cochran's Q test, while pleiotropy was assessed by MR-Egger regression. Sensitivity analysis was performed by weighted median method, MR-Egger method, simple mode method, weighted mode method, and leave-one-out analysis method.

Results: Mendelian randomization results showed positive causal associations between PM10 with hypertension (OR: 1.49; 95%CI: 1.06, 2.09; : 2.23 × 10) and systolic blood pressure (: 1.89; 95%CI: 0.32, 3.47; : 1.85 × 10), positive causal associations between PM2.5 and hypertension (OR: 1.26; 95%CI: 1.01, 2.58; : 4.30 × 10), and negative causal associations between NO and systolic blood pressure (: -1.71; 95%CI: -3.39, -0.02; : 4.74 × 10). None of the above associations were subject to pleiotropic bias, and all associations were heterogeneous except for PM10 and hypertension. The leave-one-out analysis showed that no single SNP affected the stability of the results.

Conclusion: Elevated levels of PM2.5 and PM10 have been associated with an increased risk of developing hypertension, with PM10 specifically linked to higher systolic blood pressure levels. Interestingly, NO has shown potential as a protective factor in lowering systolic blood pressure. This study clarifies the causal relationship between five air pollutants and elevated blood pressure. Ensuring good ambient air quality is essential in preventing hypertension and reducing the overall disease burden.

References

Franco C, Sciatti E, Favero G, Bonomini F, Vizzardi E, Rezzani R . Essential Hypertension and Oxidative Stress: Novel Future Perspectives. Int J Mol Sci. 2022; 23(22). PMC: 9692622. DOI: 10.3390/ijms232214489. View

Hemani G, Zheng J, Elsworth B, Wade K, Haberland V, Baird D . The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018; 7. PMC: 5976434. DOI: 10.7554/eLife.34408. View

Zhou B, Perel P, Mensah G, Ezzati M . Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021; 18(11):785-802. PMC: 8162166. DOI: 10.1038/s41569-021-00559-8. View

Xia Z, Liu Y, Liu C, Dai Z, Liang X, Zhang N . The causal effect of air pollution on the risk of essential hypertension: a Mendelian randomization study. Front Public Health. 2024; 12:1247149. PMC: 10903282. DOI: 10.3389/fpubh.2024.1247149. View

Landrigan P, Fuller R, Acosta N, Adeyi O, Arnold R, Basu N . The Lancet Commission on pollution and health. Lancet. 2017; 391(10119):462-512. DOI: 10.1016/S0140-6736(17)32345-0. View

Sarathy H, Abu Salman L, Lee C, Cohen J . Evaluation and Management of Secondary Hypertension. Med Clin North Am. 2022; 106(2):269-283. PMC: 9728017. DOI: 10.1016/j.mcna.2021.11.004. View

Davey Smith G, Hemani G . Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014; 23(R1):R89-98. PMC: 4170722. DOI: 10.1093/hmg/ddu328. View

Burgess S, Dudbridge F, Thompson S . Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med. 2015; 35(11):1880-906. PMC: 4832315. DOI: 10.1002/sim.6835. View

Nakagomi A, Yasufuku Y, Ueno T, Kondo K . Social determinants of hypertension in high-income countries: A narrative literature review and future directions. Hypertens Res. 2022; 45(10):1575-1581. PMC: 9296364. DOI: 10.1038/s41440-022-00972-7. View

10.

Xu J, Niehoff N, White A, Werder E, Sandler D . Fossil-fuel and combustion-related air pollution and hypertension in the Sister Study. Environ Pollut. 2022; 315:120401. PMC: 9746069. DOI: 10.1016/j.envpol.2022.120401. View

11.

Zheng J, Baird D, Borges M, Bowden J, Hemani G, Haycock P . Recent Developments in Mendelian Randomization Studies. Curr Epidemiol Rep. 2017; 4(4):330-345. PMC: 5711966. DOI: 10.1007/s40471-017-0128-6. View

12.

Chan S, Van Hee V, Bergen S, Szpiro A, DeRoo L, London S . Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study. Environ Health Perspect. 2015; 123(10):951-8. PMC: 4590742. DOI: 10.1289/ehp.1408125. View

13.

Cai Y, Zhang B, Ke W, Feng B, Lin H, Xiao J . Associations of Short-Term and Long-Term Exposure to Ambient Air Pollutants With Hypertension: A Systematic Review and Meta-Analysis. Hypertension. 2016; 68(1):62-70. DOI: 10.1161/HYPERTENSIONAHA.116.07218. View

14.

Rodriguez-Iturbe B, Pons H, Johnson R . Role of the Immune System in Hypertension. Physiol Rev. 2017; 97(3):1127-1164. PMC: 6151499. DOI: 10.1152/physrev.00031.2016. View

15.

Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J . A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017; 36(11):1783-1802. PMC: 5434863. DOI: 10.1002/sim.7221. View

16.

Boef A, Dekkers O, le Cessie S . Mendelian randomization studies: a review of the approaches used and the quality of reporting. Int J Epidemiol. 2015; 44(2):496-511. DOI: 10.1093/ije/dyv071. View

17.

Tsounis D, Bouras G, Giannopoulos G, Papadimitriou C, Alexopoulos D, Deftereos S . Inflammation markers in essential hypertension. Med Chem. 2014; 10(7):672-81. DOI: 10.2174/1573406410666140318111328. View

18.

Hu X, Nie Z, Ou Y, Qian Z, McMillin S, Aaron H . Air quality improvement and cognitive function benefit: Insight from clean air action in China. Environ Res. 2022; 214(Pt 4):114200. DOI: 10.1016/j.envres.2022.114200. View

19.

Eeftens M, Beelen R, de Hoogh K, Bellander T, Cesaroni G, Cirach M . Development of Land Use Regression models for PM(2.5), PM(2.5) absorbance, PM(10) and PM(coarse) in 20 European study areas; results of the ESCAPE project. Environ Sci Technol. 2012; 46(20):11195-205. DOI: 10.1021/es301948k. View

20.

Nugroho P, Andrew H, Kohar K, Noor C, Sutranto A . Comparison between the world health organization (WHO) and international society of hypertension (ISH) guidelines for hypertension. Ann Med. 2022; 54(1):837-845. PMC: 8933011. DOI: 10.1080/07853890.2022.2044510. View