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Mediating effect of telomere length in a hypertension population exposed to cadmium: a case–control study


Cadmium (Cd) is associated with telomere length and hypertension, respectively, but the mechanism behind its relationship is unclear. Our study aimed to clarify the role of telomere length in the relationship between Cd and hypertension. A 1:1 matched case–control study was conducted with 213 hypertensive patients and 213 normotensive controls in Taiyuan, Shanxi Province, China, from February and June 2016. General demographic characteristics information and lifestyle were collected using a structured questionnaire. Urine samples were collected to test urinary Cd (UCd) levels and corrected by urinary creatinine (UCr) levels. Peripheral leukocyte absolute telomere length (ATL) was measured using quantitative polymerase chain reaction. Logistic regression was used to screen the influencing factors of hypertension. A mediation effect analysis was used to explore the role of telomere length between Cd exposure and the risk of hypertension. We found that the hypertension group had a significantly higher UCd level compared to the control group (0.91 vs 0.80 μg/g Cr, P < 0.01), while ATL showed the opposite relationship (2.36 vs 2.65 kb, P < 0.01). The Regression analysis of hypertension identified these significant predictors: family history of hypertension (OR = 3.129, 95% confidence interval (95% CI): 1.767–5.540), Body mass index (BMI, OR = 1.088, 95% CI: 1.023–1.157), total cholesterol (TC, OR = 1.277, 95% CI: 1.024–1.592), UCd (OR = 2.092, 95% CI: 1.179–3.710), ATL (OR = 0.105, 95% CI: 0.025–0.453) and 8-hydroxy-2-deoxyguanosine (8-OHdG, OR = 7.864, 95% CI: 3.516–17.589). Mediating effect analysis revealed that ATL was a potential partial mediating factor between Cd and hypertension. Cd may induce hypertension by affecting telomere length, but this requires further exploration.

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Fig. 1: Mediating effect model.
Fig. 2: Relationship between UCd, ATL, and blood pressure.
Fig. 3: Scatter plot of correlation between UCd and ATL in the control and hypertension groups.
Fig. 4: ATL as a mediator between cadmium and hypertension.

Data availability

If additional data are available from the corresponding author on reasonable request.


  1. Yin R, Yin L, Li L, Silva-Nash J, Tan J, Pan Z, et al. Hypertension in China: burdens, guidelines and policy responses: a state-of-the-art review. J Hum Hypertens. 2022;36:126–34.

    Article  Google Scholar 

  2. Luo Y, Xia F, Yu X, Li P, Huang W, Zhang W. Long-term trends and regional variations of hypertension incidence in China: a prospective cohort study from the China Health and Nutrition Survey, 1991-2015. BMJ Open. 2021;11:e042053.

    Article  Google Scholar 

  3. Liew SJ, Lee JT, Tan CS, Koh CHG, Van Dam R, Muller-Riemenschneider F. Sociodemographic factors in relation to hypertension prevalence, awareness, treatment and control in a multi-ethnic Asian population: a cross-sectional study. BMJ Open. 2019;9:e025869.

    Article  Google Scholar 

  4. Yu C, Zhao H, Pan L, Zhang J, Wang X, Chang L, et al. The additive interaction between body mass index and hypertension family history in Han and Yugur: The China National Health Survey (CNHS). Int J Hypertens. 2019;2019:1–9.

    Article  Google Scholar 

  5. Lin Y, Mei Q, Qian X, He T. Salt consumption and the risk of chronic diseases among Chinese adults in Ningbo city. Nutr J. 2020;19:9.

    CAS  Article  Google Scholar 

  6. Yousefi M, Najafi Saleh H, Yaseri M, Jalilzadeh M, Mohammadi AA. Association of consumption of excess hard water, body mass index and waist circumference with risk of hypertension in individuals living in hard and soft water areas. Environ Geochem Health. 2019;41:1213–21.

    CAS  Article  Google Scholar 

  7. Xiao L, Li W, Zhu C, Yang S, Zhou M, Wang B, et al. Cadmium exposure, fasting blood glucose changes, and type 2 diabetes mellitus: a longitudinal prospective study in China. Environ Res. 2021;192:110259.

    CAS  Article  Google Scholar 

  8. Zhong Q, Wu HB, Niu QS, Jia PP, Qin QR, Wang XD, et al. Exposure to multiple metals and the risk of hypertension in adults: a prospective cohort study in a local area on the Yangtze River, China. Environ Int. 2021;153:106538.

    CAS  Article  Google Scholar 

  9. Chen X, Zhu G, Lei L, Jin T. The association between blood pressure and blood cadmium in a Chinese population living in cadmium polluted area. Environ Toxicol Pharm. 2013;36:595–9.

    CAS  Article  Google Scholar 

  10. Little BB, Reilly R, Walsh B, Vu GT. Cadmium is associated with type 2 diabetes in a superfund site lead smelter community in Dallas, Texas. Int J Environ Res Public Health. 2020;17:4558.

    CAS  Article  Google Scholar 

  11. Morgan RG, Ives SJ, Walker AE, Cawthon RM, Andtbacka RH, Noyes D, et al. Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J Hypertens. 2014;32:1293–9.

    CAS  Article  Google Scholar 

  12. Liu P, Zhang Y, Ma L. Telomere length and associated factors in older adults with hypertension. J Int Med Res. 2019;47:5465–74.

    CAS  Article  Google Scholar 

  13. Filipic M. Mechanisms of cadmium induced genomic instability. Mutat Res. 2012;733:69–77.

    CAS  Article  Google Scholar 

  14. Chen JH, Hales CN, Ozanne SE. DNA damage, cellular senescence and organismal ageing: causal or correlative? Nucleic Acids Res. 2007;35:7417–28.

    CAS  Article  Google Scholar 

  15. Zgheib NK, Sleiman F, Nasreddine L, Nasrallah M, Nakhoul N, Isma’eel H, et al. Short telomere length is associated with aging, central obesity, poor sleep and hypertension in Lebanese individuals. Aging Dis. 2018;9:77–89.

    Article  Google Scholar 

  16. Rizvi S, Raza ST, Mahdi F. Telomere length variations in aging and age-related diseases. Curr Aging Sci. 2014;7:161–7.

    CAS  Article  Google Scholar 

  17. O’Callaghan NJ, Fenech M. A quantitative PCR method for measuring absolute telomere length. Biol Proced Online. 2011;13:3.

    Article  Google Scholar 

  18. Fang J, Wen ZL, Zhang MQ. Analysis method of mediating effect of categorical variables. J Psychol Sci. 2017;40:471–7. in Chinese.

    Google Scholar 

  19. Tofighi D, MacKinnon DP. RMediation: an R package for mediation analysis confidence intervals. Behav Res Methods. 2011;43:692–700.

    Article  Google Scholar 

  20. Chen X, Wang Z, Zhu G, Liang Y, Jin T. Benchmark dose estimation of cadmium reference level for hypertension in a Chinese population. Environ Toxicol Pharm. 2015;39:208–12.

    CAS  Article  Google Scholar 

  21. Caciari T, Sancini A, Fioravanti M, Capozzella A, Casale T, Montuori L, et al. Cadmium and hypertension in exposed workers: a meta-analysis. Int J Occup Med Environ Health. 2013;26:440–56.

    Article  Google Scholar 

  22. Xu Y, Zhou X, Zheng Y, Guan H, Fu C, Xiao J, et al. The association of urinary uric acid excretion with ambulatory blood pressure values in patients with chronic kidney disease. Clin Hypertens. 2020;26:4.

    Article  Google Scholar 

  23. Giaginis C, Gatzidou E, Theocharis S. DNA repair systems as targets of cadmium toxicity. Toxicol Appl Pharm. 2006;213:282–90.

    CAS  Article  Google Scholar 

  24. Lu S, Ren L, Fang J, Ji J, Liu G, Zhang J, et al. Trace elements are associated with urinary 8-hydroxy-2’-deoxyguanosine level: a case study of college students in Guangzhou, China. Environ Sci Pollut Res Int. 2016;23:8484–91.

    CAS  Article  Google Scholar 

  25. Su TY, Pan CH, Hsu YT, Lai CH. Effects of heavy metal exposure on shipyard welders: a cautionary note for 8-hydroxy-2’-deoxyguanosine. Int J Environ Res Public Health. 2019;16:4813.

    CAS  Article  Google Scholar 

  26. Pinheiro Junior JEG, Moraes PZ, Rodriguez MD, Simoes MR, Cibin F, Pinton S, et al. Cadmium exposure activates NADPH oxidase, renin-angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage. Toxicol Lett. 2020;333:80–9.

    CAS  Article  Google Scholar 

  27. Skipper A, Sims JN, Yedjou CG, Tchounwou PB. Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress. Int J Environ Res Public Health. 2016;13:88.

    Article  Google Scholar 

  28. Kimura M, Barbieri M, Gardner JP, Skurnick J, Cao X, van Riel N, et al. Leukocytes of exceptionally old persons display ultra-short telomeres. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2210–7.

    CAS  Article  Google Scholar 

  29. Li A, Peng Q, Shao Y, Zhang Y, Fang X. Association between family history and the onset age of essential hypertension in Han population in Shanghai China. Am J Health Res. 2019;7:79–84.

    Article  Google Scholar 

  30. Huang J, Bao X, Xie Y, Zhang X, Peng X, Liu Y, et al. Interaction of lipid accumulation product and family history of hypertension on hypertension risk: a cross-sectional study in the Southern Chinese population. BMJ Open. 2019;9:e029253.

    Article  Google Scholar 

  31. Liang H, Yue R, Zhou C, Liu M, Yu X, Lu S, et al. Cadmium exposure induces endothelial dysfunction via disturbing lipid metabolism in human microvascular endothelial cells. J Appl Toxicol. 2021;41:775–88.

    CAS  Article  Google Scholar 

  32. Hong X, Wongtongkam N, Ward PR, Xiaio S, Wang S, Peng Q, et al. Association of demographic, lifestyle factors and serum biomarkers with hypertension in elderly Chinese people. Ageing Soc. 2017;37:661–74.

    Article  Google Scholar 

  33. Otsuka T, Takada H, Nishiyama Y, Kodani E, Saiki Y, Kato K, et al. Dyslipidemia and the risk of developing hypertension in a working-age male population. J Am Heart Assoc. 2016;5:e003053.

    Article  Google Scholar 

  34. Zota AR, Needham BL, Blackburn EH, Lin J, Park SK, Rehkopf DH, et al. Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999-2002. Am J Epidemiol. 2015;181:127–36.

    Article  Google Scholar 

  35. Huang B, Sivaganesan S, Succop P, EJSiM G. Statistical assessment of mediational effects for logistic mediational models. Stat Med. 2004;23:2713–28.

    Article  Google Scholar 

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We sincerely thank all study participants for providing information and biological samples. In addition, we particularly appreciate the fund projects that provide funds and experimental research equipment. Finally, we thank all the authors participating in this project for their efforts.


This work was supported by the National Natural Science Foundation of China [grant number 81273040, 81872701]; Research project of postgraduate education reform in Shanxi province [grant number 2018JG47].

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Authors and Affiliations



LJL and LNM conceived the idea, designed, and instructed the study, contributed to interpretation of results. RJL, HK, ZZ, YYG, and ZCH participated in the sample collection and collation. QY, RJL, YYG, YFZ, and YXL, contributed to the experimental technology and substances. QY and RJL conducted a global and careful analysis of the data. QY wrote the article, and all the authors checked and approved the final manuscript.

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Correspondence to Lina Mu or Lijian Lei.

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Yang, Q., Liu, R., Gao, Y. et al. Mediating effect of telomere length in a hypertension population exposed to cadmium: a case–control study. J Hum Hypertens (2022).

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