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Association between growth hormone and hypertension in a general population

Hypertension Research volume 43, pages 1430–1436 (2020)Cite this article

Abstract

Insulin-like growth factors are polypeptides, with arrays similar to insulin, and insulin-like growth factor 1 (IGF-1) is secreted via stimulation by growth hormone (GH) in the liver. The lack of both GH and IGF-1 leads to physiological age-related changes in the cardiovascular system; however, the role of IGF-1 and GH in hypertension has not been fully elucidated. Thus, we examined the association between plasma IGF-1 and GH levels and hypertension. Among 1368 health check-up examination participants in the town of Tanushimaru, 1094 subjects were analyzed after excluding subjects with diabetes mellitus or impaired liver function. Multiple linear and logistic regression analyses were performed for factors related to systolic and diastolic blood pressures (BPs). Characteristics of participants stratified by IGF-1 and GH quartiles were compared using analysis of covariance. We calculated odds ratios associated with each standard deviation increase in IGF-1 and GH levels for hypertension, which was defined as BP ≥ 140/90 mmHg and/or the use of antihypertensive medication. Multivariable analysis showed that FPG, insulin, HOMA-IR, eGFR, total cholesterol, triglycerides, and the use of medication for hypertension were associated with the Z-score of IGF-1 measurement quartiles. Next, we found that BMI, systolic and diastolic BPs, insulin, HOMA-IR, total cholesterol, HDL-cholesterol, triglycerides, smoking, and alcohol intake were associated with GH quartiles, indicating that hypertension was inversely associated with GH but not IGF-1. A significant and inverse relationship between serum GH and hypertension was found after adjustment for confounders. In conclusion, decreased GH but not IGF-1, was associated with hypertension in a general population.

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References

  1. Rudman D. Growth hormone, body composition, and aging. J Am Geriatr Soc. 1985;33:800–7.

    Article  CAS  Google Scholar 

  2. Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Investig. 1981;67:1361–9.

    Article  CAS  Google Scholar 

  3. Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, et al. Effects of human growth hormone in men over 60 years old. N. Engl J Med. 1990;323:1–6.

    Article  CAS  Google Scholar 

  4. Florini JR, Prinz PN, Vitiello MV, Hintz RL. Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol. 1985;40:2–7.

    Article  CAS  Google Scholar 

  5. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: The Rancho Bernardo Study. J Clin Endocrinol Metab. 2004;89:114–20.

    Article  CAS  Google Scholar 

  6. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. 1995;16:143–63.

    Article  CAS  Google Scholar 

  7. Caicedo D, Díaz O, Devesa P, Devesa J. Growth hormone (GH) and cardiovascular system. Int J Mol Sci. 2018;19:E290.

    Article  Google Scholar 

  8. Rizza RA, Mandarino LJ, Gerich JE. Effects of growth hormone on insulin action in man. Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes. 1982;31:663–9.

    Article  CAS  Google Scholar 

  9. Ciresi A, Radellini S, Guarnotta V, Giordano C. The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency. Endocrine. 2017;56:579–88.

    Article  CAS  Google Scholar 

  10. Isgaard J. Cardiovascular disease and risk factors: the role of growth hormone. Horm Res. 2004;62:31–8.

    Article  CAS  Google Scholar 

  11. Toshima H, Tashiro H, Sumie M, Koga Y, Kimura N. Nutritional prevention of cardiovascular disease. In: Lovenberg W, Yamori Y, (eds). Changes in risk factors and cardiovascular mortality and morbidity within Tanushimaru 1958-1982. New York: Academic Press; 1984. pp. 203–10.

    Google Scholar 

  12. Hirai Y, Geleijnse JM, Adachi H, Imaizumi T, Kromhout D. Systolic blood pressure predicts cardiovascular mortality in a farming but not in a fishing community. A 40-year follow up of the Japanese cohorts of the seven countries study-. Circ J. 2011;75:1890–6.

    Article  Google Scholar 

  13. Adachi H, Enomoto M, Fukami A, Kumagai E, Nakamura S, Yoshimura A, et al. Plasma renin activity and resting heart rate in a population of community-dwelling Japanese: The Tanushimaru Study. Am J Hypertens. 2015;28:894–9.

    Article  CAS  Google Scholar 

  14. Nakamura S, Adachi H, Enomoto M, Fukami A, Kumagai E, Nohara Y, et al. Trends in coronary risk factors and electrocardiogram findings from 1977 to 2009 with 10-year mortality in Japanese elderly males—The Tanushimaru Study. J Cardiol. 2017;70:353–8.

    Article  Google Scholar 

  15. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.

    Article  CAS  Google Scholar 

  16. Guha N. Assays for GH, IGF-I, and IGF binding protein-3. Methods Mol Biol. 2013;1065:117–28.

    Article  CAS  Google Scholar 

  17. McGrath MF, Bogosian G, Fabellar AC, Staub RL, Vicini JL, Widger LA. Measurement of bovine somatotropin (bST) and insulin-like growth factor-1 (IGF-1) in bovine milk using an electrochemiluminescent assay. J Agric Food Chem. 2008;56:7044–8.

    Article  CAS  Google Scholar 

  18. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  Google Scholar 

  19. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  Google Scholar 

  20. Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, Hizuka N, et al. Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J. 2012;59:771–80.

    Article  CAS  Google Scholar 

  21. Page JH, Ma J, Pollak M, Manson JE, Hankinson SE. Plasma insulinlike growth factor 1 and binding-protein 3 and risk of myocardial infarction in women: a prospective study. Clin Chem. 2008;54:1682–8.

    Article  CAS  Google Scholar 

  22. Ameri P, Canepa M, Fabbi P, Leoncini G, Milaneschi Y, Mussap M, et al. Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness. Atherosclerosis. 2014;236:418–25.

    Article  CAS  Google Scholar 

  23. Bian A, Ma Y, Zhou X, Guo Y, Wang W, Zhang Y, et al. Association between sarcopenia and levels of growth hormone and insulin-like growth factor-1 in the elderly. BMC Musculoskelet Disord. 2020;21:214.

    Article  CAS  Google Scholar 

  24. Schneider DJ, Sobel BE. Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: implications for vascular disease in hyperinsulinemic states. Proc Natl Acad Sci USA. 1991;88:9959–63.

    Article  CAS  Google Scholar 

  25. Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Investig. 1995;95:2266–74.

    Article  CAS  Google Scholar 

  26. Colangelo LA, Liu K, Gapstur SM, CARDIA Male Hormone Study. Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and cardiovascular disease risk factors in young black men and white men: the CARDIA Male Hormone Study. Am J Epidemiol. 2004;160:750–7.

    Article  Google Scholar 

  27. Erlandsson MC, Lyngfelt L, Åberg ND, Wasén C, Espino RA, Silfverswärd ST, et al. Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis. BMC Med. 2019;17:141.

    Article  Google Scholar 

  28. Strazhesko ID, Tkacheva ON, Akasheva DU, Dudinskaya EN, Plokhova EV, Pykhtina VS, et al. Growth hormone, insulin-like growth factor-1, insulin resistance, and leukocyte telomere length as determinants of arterial aging in subjects free of cardiovascular diseases. Front Genet. 2017;8:198.

    Article  Google Scholar 

  29. van der Klaauw AA, Biermasz NR, Feskens EJ, Bos MB, Smit JW, Roelfsema F, et al. The prevalence of the metabolic syndrome is increased in patients with GH deficiency, irrespective of long-term substitution with recombinant human GH. Eur J Endocrinol. 2007;156:455–62.

    Article  Google Scholar 

  30. Irie M, Itoh Y, Miyashita Y, Tsushima T, Shirai K. Complications in adults with growth hormone deficiency—A Survey Study in Japan. Endocr J. 2004;51:479–85.

    Article  Google Scholar 

  31. McCarty MF. IGF-I activity may be a key determinant of stroke risk—a cautionary lesson for vegans. Med Hypotheses. 2003;61:323–34.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by the Kimura Memorial Heart Foundation, Fukuoka, Japan, and by a Grant-in-Aid for Scientific Research (C), from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We are grateful to the members of the Japan Medical Association of Ukiha, the elected officials and residents of Tanushimaru, and the team of physicians who carried out the health examinations.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan

    Hideki Ohshima, Hisashi Adachi, Mika Enomoto, Ako Fukami, Sachiko Nakamura, Yume Nohara, Akiko Sakaue, Nagisa Morikawa, Hitoshi Hamamura, Kenta Toyomasu, Maki Yamamoto & Yoshihiro Fukumoto

  2. Department of Community Medicine, Kurume University School of Medicine, Kurume, Japan

    Hisashi Adachi

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  1. Hideki Ohshima
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Ohshima, H., Adachi, H., Enomoto, M. et al. Association between growth hormone and hypertension in a general population. Hypertens Res 43, 1430–1436 (2020). https://doi.org/10.1038/s41440-020-0500-7

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