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Associations of maternal liver biomarkers in the first trimester with the risk of hypertensive disorders of pregnancy

Hypertension Research volume 47, pages 2183–2194 (2024)Cite this article

A Comment to this article was published on 23 July 2024

Abstract

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23–2.41), 1.53-fold (95% Cl: 1.10–2.14), 0.62-fold (95% Cl: 0.43–0.90) and 1.67-fold (95% Cl: 1.05–2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (Pinteraction = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP.

Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP.

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Data availability

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

  1. Umesawa M, Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res. 2017;40:213–20.

    Article  PubMed  Google Scholar 

  2. Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2:e323–33.

    Article  PubMed  Google Scholar 

  3. Metoki H, Iwama N, Hamada H, Satoh M, Murakami T, Ishikuro M, et al. Hypertensive disorders of pregnancy: definition, management, and out-of-office blood pressure measurement. Hypertens Res. 2022;45:1298–309.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Agrawal A, Wenger NK. Hypertension During Pregnancy. Curr Hypertens Rep. 2020;22:64.

    Article  PubMed  Google Scholar 

  5. Lo CCW, Lo ACQ, Leow SH, Fisher G, Corker B, Batho O, et al. Future Cardiovascular Disease Risk for Women With Gestational Hypertension: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2020;9:e013991.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cheung CL, Tan KC, Lam KS, Cheung BM. The relationship between glucose metabolism, metabolic syndrome, and bone-specific alkaline phosphatase: a structural equation modeling approach. J Clin Endocrinol Metab. 2013;98:3856–63.

    Article  CAS  PubMed  Google Scholar 

  7. Arinc H, Sarli B, Baktir AO, Saglam H, Demirci E, Dogan Y, et al. Serum gamma glutamyl transferase and alanine transaminase concentrations predict endothelial dysfunction in patients with non-alcoholic steatohepatitis. Ups J Med Sci. 2013;118:228–34.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H, et al. Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005;112:2130–7.

    Article  CAS  PubMed  Google Scholar 

  9. Cho GJ, Kim HY, Park JH, Ahn KH, Hong SC, Oh MJ, et al. Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: A population-based cohort study. Liver Int. 2018;38:949–54.

    Article  CAS  PubMed  Google Scholar 

  10. Lee SM, Park JS, Han YJ, Kim W, Bang SH, Kim BJ, et al. Elevated Alanine Aminotransferase in Early Pregnancy and Subsequent Development of Gestational Diabetes and Preeclampsia. J Korean Med Sci. 2020;35:e198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen Y, Ou W, Lin D, Lin M, Huang X, Ni S, et al. Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia. Front Cardiovasc Med. 2021;8:756140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Metra BM, Guglielmo FF, Halegoua-DeMarzio DL, Civan JM, Mitchell DG. Beyond the Liver Function Tests: A Radiologist’s Guide to the Liver Blood Tests. Radiographics. 2022;42:125–42.

    Article  PubMed  Google Scholar 

  13. Stranges S, Trevisan M, Dorn JM, Dmochowski J, Donahue RP. Body fat distribution, liver enzymes, and risk of hypertension: evidence from the Western New York Study. Hypertension. 2005;46:1186–93.

    Article  CAS  PubMed  Google Scholar 

  14. Shao B, Jiang S, Muyiduli X, Wang S, Mo M, Li M, et al. Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women. Clin Nutr. 2018;37:2230–7.

    Article  CAS  PubMed  Google Scholar 

  15. Jones GS, Alvarez CS, Graubard BI, McGlynn KA. Agreement Between the Prevalence of Nonalcoholic Fatty Liver Disease Determined by Transient Elastography and Fatty Liver Indices. Clin Gastroenterol Hepatol. 2022;20:227–9.e2.

    Article  CAS  PubMed  Google Scholar 

  16. Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42:503–8.

    Article  CAS  PubMed  Google Scholar 

  17. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. 2018;72:24–43.

    Article  CAS  PubMed  Google Scholar 

  18. Si S, Mo M, Cheng H, Peng Z, Alifu X, Zhou H, et al. The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study. Nutrients. 2022;14:2355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang Y, Sheng C, Wang D, Chen X, Jiang Y, Dou Y, et al. High-normal liver enzyme levels in early pregnancy predispose the risk of gestational hypertension and preeclampsia: A prospective cohort study. Front Cardiovasc Med. 2022;9:963957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Whitfield JB. Gamma glutamyl transferase. Crit Rev Cl Lab Sci. 2001;38:263–355.

    Article  CAS  Google Scholar 

  21. Sabanayagam C, Shankar A, Li J, Pollard C, Ducatman A. Serum gamma-glutamyl transferase level and diabetes mellitus among US adults. Eur J Epidemiol. 2009;24:369–73.

    Article  CAS  PubMed  Google Scholar 

  22. Schoppet M, Shanahan CM. Role for alkaline phosphatase as an inducer of vascular calcification in renal failure? Kidney Int. 2008;73:989–91.

    Article  CAS  PubMed  Google Scholar 

  23. Filipowicz R, Greene T, Wei G, Cheung AK, Raphael KL, Baird BC, et al. Associations of serum skeletal alkaline phosphatase with elevated C-reactive protein and mortality. Clin J Am Soc Nephrol. 2013;8:26–32.

    Article  CAS  PubMed  Google Scholar 

  24. Ndrepepa G, Colleran R, Kastrati A. Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease. Clin Chim Acta. 2018;476:130–8.

    Article  CAS  PubMed  Google Scholar 

  25. Goins EC, Wein LE, Watkins VY, Campbell AIK, Heine RP, Hughes BL, et al. Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts. Plos One. 2023;18:e0293030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kawamoto R, Kohara K, Kusunoki T, Tabara Y, Abe M, Miki T. Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults. Cardiovasc Diabetol. 2012;11:117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mei-Dan E, Wiznitzer A, Sergienko R, Hallak M, Sheiner E. Prediction of preeclampsia: liver function tests during the first 20 gestational weeks. J Matern Fetal Neona. 2013;26:250–3.

    Article  CAS  Google Scholar 

  28. Jung YM, Lee SM, Hong S, Koo JN, Oh IH, Kim BJ, et al. The risk of pregnancy-associated hypertension in women with nonalcoholic fatty liver disease. Liver Int. 2020;40:2417–26.

    Article  CAS  PubMed  Google Scholar 

  29. Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42:473–80.

    Article  PubMed  Google Scholar 

  30. Brea A, Mosquera D, Martín E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis -: A case-control study. Arterioscl Throm Vas. 2005;25:1045–50.

    Article  CAS  Google Scholar 

  31. Kral JG, Schaffner F, Pierson RN Jr, Wang J. Body fat topography as an independent predictor of fatty liver. Metabolism. 1993;42:548–51.

    Article  CAS  PubMed  Google Scholar 

  32. Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H, et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol. 2002;17:1098–105.

    Article  PubMed  Google Scholar 

  33. Landsberg L, Aronne LJ, Beilin LJ, Burke V, Igel LI, Lloyd-Jones D, et al. Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment-a position paper of the The Obesity Society and The American Society of Hypertension. Obesity. 2013;21:8–24.

    Article  PubMed  Google Scholar 

  34. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98:960–7.

    Article  CAS  PubMed  Google Scholar 

  35. Powell-Wiley TM, Poirier P, Burke LE, Despres JP, Gordon-Larsen P, Lavie CJ, et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;143:e984–e1010.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang Z, Zeng X, Chen Z, Wang X, Zhang L, Zhu M, et al. Association of visceral and total body fat with hypertension and prehypertension in a middle-aged Chinese population. J Hypertens. 2015;33:1555–62.

    Article  CAS  PubMed  Google Scholar 

  37. Seravalle G, Grassi G. Obesity and hypertension. Pharm Res. 2017;122:1–7.

    Article  CAS  Google Scholar 

  38. Yang Y, Le Ray I, Zhu J, Zhang J, Hua J, Reilly M. Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China. JAMA Netw Open. 2021;4:e218401.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We deeply appreciate the clinicians and all participants in Zhoushan.

Funding

This research was funded by the National Key Research and Development Program of China (grant number: 2022YFC2703505 and 2021YFC2701901); National Natural Science Foundation of China (grant number: 82103807); Major research and development projects of Zhejiang Science and Technology Department (grant number: 2018C03010); Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province (grant number: 2020E10004); Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (grant number: 2019R01007).

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Author notes

  1. These authors contributed equally: Hui Liu, Libi Zhang

Authors and Affiliations

  1. Clinical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Hui Liu

  2. Department of Public Health, and Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

    Libi Zhang, Diliyaer Ainiwan, Peihan Chi, Haoyue Cheng, Xialidan Alifu, Yiwen Qiu, Ye Huang, Yan Zhuang, Haibo Zhou & Yunxian Yu

  3. Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China

    Libi Zhang, Diliyaer Ainiwan, Peihan Chi, Haoyue Cheng, Xialidan Alifu, Yiwen Qiu, Ye Huang, Yan Zhuang, Haibo Zhou & Yunxian Yu

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Contributions

LZ conducted data analysis and wrote the first draft. HL designed the research plan and reviewed and revised the manuscript. HC, PC and DA were responsible for data collection and review the data analysis. XA, YQ, YH, YZ, and HZ participated in the interpretation of data and review of the manuscript. YY reviewed and finalized manuscript. YY is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Yunxian Yu.

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The authors declare no competing interests.

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The work was conducted according to the Declaration of Helsinki and has been approved by the Institutional Review Board of Zhoushan Maternal and Child Health Care Hospital (Ethical Approval Code: 2011-05).

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Liu, H., Zhang, L., Ainiwan, D. et al. Associations of maternal liver biomarkers in the first trimester with the risk of hypertensive disorders of pregnancy. Hypertens Res 47, 2183–2194 (2024). https://doi.org/10.1038/s41440-024-01722-7

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