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The independent association between salivary alpha-amylase activity and arterial stiffness in Japanese men and women: the Toon Health Study

A Comment to this article was published on 16 August 2022

Abstract

Psychological stress is considered to be a potential contributor in the development of arterial stiffness. However, an independent association between arterial stiffness and biological markers of stress has not yet been established. We examined the independent association between salivary alpha-amylase (sAA) activity and arterial stiffness, not mediated by cardiometabolic disease associated with arterial stiffness, in a sample of healthy Japanese men and women. Participants (992 in total, 296 men and 696 women aged 30–79 years) had neither previous cardiovascular events or stroke, nor coexisting hypertension, diabetes, or dyslipidemia. Arterial stiffness was measured by the cardio-ankle vascular index (CAVI), and increased CAVI was defined as a CAVI value of 9 or higher. A saliva sample was collected in the morning and sAA was measured with a commercial assay kit. Higher sAA activity was positively associated with greater arterial stiffness particularly among women (β = 0.070; 95% CI = 0.014–0.126; p = 0.01), and not across all participants (β = 0.042; 95% CI = −0.005–0.089; p = 0.08) and in men (β = −0.005; 95% CI = −0.097–0.087; p = 0.91). The association was strongest in the group of women aged 60 years and older (β = 0.121; 95% CI = 0.018–0.224; p = 0.02). Although the association between sAA and increased CAVI (CAVI ≥ 9) was not significant in all and sex subgroups, odds ratios (OR) for CAVI ≥ 7 were significantly high in all participants (OR = 1.25; 95% CI = 1.03–1.53) and women (OR = 1.43; 95% CI = 1.12–1.82). Elevation of sAA was associated with an increase in arterial stiffness, particularly for women aged 60 years or older.

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References

  1. World Health Organization: The top 10 causes of death. 9 December 2020. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (accessed May 13, 2022).

  2. Ministry of Health, Labour and Welfare: Demographis statistics in 2019. https://www.mhlw.go.jp/toukei/saikin/hw/jinkou/geppo/nengai19/dl/gaikyouR1.pdf. (accessed May 13, 2022) (in Japanese).

  3. Matsushita K, Ding N, Kim ED, Budoff M, Chirinos JA, Fernhall B, et al. Cardio-ankle vascular index and cardiovascular disease: Systematic review and meta-analysis of prospective and cross-sectional studies. J Clin Hypertens (Greenwich). 2019;21:16–24.

    Article  CAS  Google Scholar 

  4. Shirai K, Hiruta N, Song M, Kurosu T, Suzuki J, Tomaru T, et al. Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives. J Atheroscler Thromb. 2011;18:924–38.

    Article  PubMed  Google Scholar 

  5. Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, et al. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23:233–46.

    Article  CAS  PubMed  Google Scholar 

  6. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012;9:360–70.

    Article  CAS  PubMed  Google Scholar 

  7. Kivimäki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol. 2018;15:215–29.

    Article  PubMed  CAS  Google Scholar 

  8. Chinnaiyan KM. Role of stress management for cardiovascular disease prevention. Curr Opin Cardiol. 2019;34:531–5.

    Article  PubMed  Google Scholar 

  9. Kume D, Nishiwaki M, Hotta N, Endoh H. Impact of acute mental stress on segmental arterial stiffness. Eur J Appl Physiol. 2020;120:2247–57.

    Article  PubMed  Google Scholar 

  10. Shimizu K, Takahashi M, Shirai K. A huge earthquake hardened arterial stiffness monitored with cardio-ankle vascular index. J Atheroscler Thromb. 2013;20:503–11.

    Article  PubMed  Google Scholar 

  11. Binder EB, Nemeroff CB. The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol Psychiatry. 2010;15:574–88.

    Article  CAS  PubMed  Google Scholar 

  12. Ali N, Nater UM. Salivary alpha-amylase as a biomarker of stress in behavioral medicine. Int J Behav Med. 2020;27:337–42.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Adam EK, Kumari M. Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology. 2009;34:1423–36.

    Article  CAS  PubMed  Google Scholar 

  14. Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. 2009;34:486–96.

    Article  CAS  PubMed  Google Scholar 

  15. Booij SH, Bos EH, Bouwmans ME, van Faassen M, Kema IP, Oldehinkel AJ, et al. Cortisol and α-amylase secretion patterns between and within depressed and non-depressed individuals. PLoS One. 2015;10:e0131002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Ikeda A, Steptoe A, Brunner EJ, Maruyama K, Tomooka K, Kato T, et al. Salivary alpha-amylase activity in relation to cardiometabolic status in Japanese adults without history of cardiovascular disease. J Atheroscler Thromb. 2020;28:852–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Saiki A, Ohira M, Yamaguchi T, Nagayama D, Shimizu N, Shirai K, et al. New horizons of arterial stiffness developed using cardio-ankle vascular index (CAVI). J Atheroscler Thromb. 2020;27:732–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Alberto EC, Tanigawa T, Maruyama K, Kawasaki Y, Eguchi E, Mori H, et al. Relationships between nocturnal intermittent hypoxia, arterial stiffness and cardiovascular risk factors in a community-based population: the toon health study. J Atheroscler Thromb. 2014;21:1290–7.

    Article  PubMed  Google Scholar 

  19. Miyano I, Takata J, Nishinaga M, Okumiya K, Hamada T, Kubo T, et al. Quantitative analysis of carotid atherosclerotic lesions and high-sensitivity C-reactive protein in community-welling elderly 80 years or older. Geriatr Gerontol Int. 2006;6:186–93.

    Article  Google Scholar 

  20. Bramwell JC, Hill AV. The velocity of pulse wave in man. Proc Roy Soc of London Series B. 1922;13:293–8.

    Google Scholar 

  21. Hayashi K, Sato M, Niimi H, Handa H, Moritake K. Analysis of the constitutive laws of the vascular wall by finite deformation theory. Iyodenshi To Seitai Kogaku. 1975;13:293–8.

    CAS  PubMed  Google Scholar 

  22. Hasegawa M. Fundamental research on human aortic pulse wave velocity. Jikei Med J. 1970;85:742–60.

    Google Scholar 

  23. Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S, et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan −2012 version. J Atheroscler Thromb. 2013;20:517–23.

    Article  PubMed  Google Scholar 

  24. Tanaka A, Tomiyama H, Maruhashi T, Matsuzawa Y, Miyoshi T, Kabutoya T. Physiological diagnosis criteria for vascular failure committee. physiological diagnostic criteria for vascular failure. Hypertension. 2018;72:1060–71.

    Article  CAS  PubMed  Google Scholar 

  25. Ishikawa-Takata K, Naito Y, Tanaka S, Ebine N, Tabata I. Use of doubly labeled water to validate a physical activity questionnaire developed for the Japanese population. J Epidemiol. 2011;21:114–21.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32:S498–504.

    Article  CAS  PubMed  Google Scholar 

  27. Otsuka K, Fukuda S, Shimada K, Suzuki K, Nakanishi K, Yoshiyama M, et al. Serial assessment of arterial stiffness by cardio-ankle vascular index for prediction of future cardiovascular events in patients with coronary artery disease. Hypertens Res. 2014;37:1014–20.

    Article  PubMed  Google Scholar 

  28. van Stegeren A, Rohleder N, Everaerd W, Wolf OT. Salivary alpha amylase as marker for adrenergic activity during stress: effect of betablockade. Psychoneuroendocrinology. 2006;31:137–41.

    Article  PubMed  CAS  Google Scholar 

  29. Giacomello G, Scholten A, Parr MK. Current methods for stress marker detection in saliva. J Pharm Biomed Anal. 2020;191:113604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Logan JG, Barksdale DJ, Carlson J, Carlson BW, Rowsey PJ. Psychological stress and arterial stiffness in Korean Americans. J Psychosom Res. 2012;73:53–58.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Logan JG, Teachman BA, Liu X, Farber CR, Liu Z, Annex BH. Acute psychological stress, autonomic function, and arterial stiffness among women. Int J Psychophysiol. 2020;155:219–26.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mozos I, Luca CT. Crosstalk between oxidative and nitrosative stress and arterial stiffness. Curr Vasc Pharmacol. 2017;15:446–56.

    Article  CAS  PubMed  Google Scholar 

  33. Shimada K, Hirano E, Kimura T, Kishimoto C. Effects of three β-blockers, propranolol, metoprolol and carvedilol, upon experimental murine atherosclerosis. Shinzou. 2013;45:519–26.

    Google Scholar 

  34. Karibe H, Aoyagi K, Koda A, Kawakami T. Characteristics of the salivary alpha-amylase level in resting sublingual saliva as an index of psychological stress. Stress Health. 2011;27:282–8.

    Article  Google Scholar 

  35. Tanaka Y, Ishitobi Y, Inoue A, Oshita H, Okamoto K, Kawashima C, et al. Sex determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with avoidant personality disorder. Brain Behav. 2016;6:e00506.

    Article  PubMed  PubMed Central  Google Scholar 

  36. O’Neil A, Scovelle AJ, Milner AJ, Kavanagh A. Gender/sex as a social determinant of cardiovascular risk. Circulation. 2018;137:854–64.

    Article  PubMed  Google Scholar 

  37. Fischer AH, Mosquera PMR, van Vianen AEM, Manstead ASR. Gender and culture differences in emotion. Emotion. 2004;4:87–94.

    Article  PubMed  Google Scholar 

  38. Ogola BO, Zimmerman MA, Clark GL, Abshire CM, Gentry KM, Miller KS, et al. New insights into arterial stiffening: does sex matter? Am J Physiol Heart Circ Physiol. 2018;315:H1073–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ober C, Loisel DA, Gilad Y. Sex-specific genetic architecture of human disease. Nat Rev Genet. 2008;9:911–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Choi SY, Oh BH, Bae Park J, Choi DJ, Rhee MY, Park S. Age-associated increase in arterial stiffness measured according to the cardio-ankle vascular index without blood pressure changes in healthy adults. J Atheroscler Thromb. 2013;20:911–23.

    Article  PubMed  CAS  Google Scholar 

  41. Ministry of Health, Labour and Welfare: National health and nutrition examination survey in 2019. https://www.mhlw.go.jp/content/10900000/000687163.pdf (accessed May 13, 2022) (in Japanese).

  42. Mandel AL, Breslin PA. High endogenous salivary amylase activity is associated with improved glycemic homeostasis following starch ingestion in adults. J Nutr. 2012;142:853–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Marquina C, Mousa A, Belski R, Banaharis H, Naderpoor N, de Courten B. Increased inflammation and cardiometabolic risk in individuals with low AMY1 copy numbers. J Clin Med. 2019;8:382.

    Article  CAS  PubMed Central  Google Scholar 

  44. van den Bos E, de Rooij M, Miers AC, Bokhorst CL, Westenberg PM. Adolescents’ increasing stress response to social evaluation: pubertal effects on cortisol and alpha-amylase during public speaking. Child Dev. 2014;85:220–36.

    Article  PubMed  Google Scholar 

  45. Bae J, Lynch CD, Kim S, Sundaram R, Sapra KJ, Buck. et al. Preconception stress and the secondary sex ratio in a population-based preconception cohort. Fertil Steril. 2017;107:714–22.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Okamoto H, Hosoda T, Teruya K, Wada T. A cross-sectional study of the association between job stress and salivary amylase activity in Japanese urban emergency medical technicians. J Kyorin Med Soc. 2015;46:149–58.

    Google Scholar 

  47. Perroni F, Tessitore A, Cibelli G, Lupo C, D’Artibale E, Cortis C, et al. Effects of simulated firefighting on the responses of salivary cortisol, alpha-amylase and psychological variables. Ergonomics. 2009;52:484–91.

    Article  CAS  PubMed  Google Scholar 

  48. Gaspar PM, Ewing E. Feasibility and usability of salivary alpha-amylase to measure stress among individuals with dementia. Res Gerontol Nurs. 2020;13:120–4.

    Article  PubMed  Google Scholar 

  49. Wan C, Couture-Lalande MÈ, Narain TA, Lebel S, Bielajew C. Salivary alpha-amylase reactivity in breast cancer survivors. Int J Environ Res Public Health. 2016;13:353.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Noto Y, Sato T, Kudo M, Kurata K, Hirota K. The relationship between salivary biomarkers and state-trait anxiety inventory score under mental arithmetic stress: a pilot study. Anesth Analg. 2005;101:1873–6.

    Article  CAS  PubMed  Google Scholar 

  51. Iso H, Date C, Yamamoto A, Toyoshima H, Tanabe N, Kikuchi S, et al. Perceived mental stress and mortality from cardiovascular disease among Japanese men and women: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Circulation. 2002;106:1229–36.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank all participants and staff members of the Toon Health Study for their painstaking efforts to conduct the baseline survey and follow-up.

Funding

This study was supported by JSPS KAKENHI Grant Numbers JP16K09072, JP17KK0175, JP18H03056, JP18K10087, and JP17K00881.

Author information

Authors and Affiliations

Authors

Contributions

T. Tajima, KT, AI, and T. Tanigawa had the original idea and developed the study design. T. Tanigawa, IS, KM, TK, and KT recruited study participants and collected data. T. Tajima performed the statistical analyses. T. Tajima wrote the first draft of the manuscript and all authors contributed to the critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takeshi Tanigawa.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was approved by the ethics committees of Juntendo University (Reference number: 2014003) and Ehime University (Reference number: 20–2).

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Appendices

Appendix 1 Association of salivary α-amylase (not log-transformed value) with CAVI (continuous values)

Table 5

Appendix 2 Scatter plot of sAA activity and CAVI value for sex and age subgroups

(A) Comparison between sAA (not log-transformed value) and natural log transformed sAA for all participants

(B) Sex and age subgroup using sAA activity (not log-transformed value)

(C) Sex and age subgroup using natural log-transformed sAA activity

Appendix 3 ROC analysis on various CAVI cut-off values

Appendix 4 Odds ratios (95% CI) of various CAVI cut-off values associated with 1-SD increment of natural log-transformed sAA

 

Total (n = 992)

Male (n = 296)

Female (n = 696)

 

Case, n

Case, %

Odds ratio (95% CI)

Case, n

Case, %

Odds ratio (95% CI)

Case, n

Case, %

Odds ratio (95% CI)

CAVI ≥ 6

971

97.9

1.31 (0.77–2.24)

294

99.3

677

97.3

1.79 (0.98–3.30)

CAVI ≥ 7

787

79.3

1.25 (1.03–1.53)

254

85.8

0.90 (0.59–1.37)

533

76.6

1.43 (1.12–1.82)

CAVI ≥ 8

416

41.9

1.05 (0.88–1.25)

154

52.0

1.02 (0.73–1.43)

262

37.6

1.13 (0.91–1.40)

CAVI ≥ 9

152

15.3

1.24 (1.00–1.53)

68

23.0

1.20 (0.86–1.66)

84

12.1

1.30 (0.97–1.76)

CAVI ≥ 10

29

2.9

1.24 (0.82–1.87)

16

5.4

0.94 (0.52–1.71)

13

1.9

1.53 (0.84–2.78)

CAVI ≥ 11

4

0.4

2.50 (0.40–15.51)

1

0.3

3

0.4

  1. adjusted by age, sex, education attainment level, marital status, employment status, BMI, smoking status, alcohol intake, physical activity, sleep, hypertension, LDL cholesterol, HDL cholesterol, triglyceride, blood glucose, and menopause status (female only). Missing data were addressed with specific dummy variables in the multivariate analyses

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Tajima, T., Ikeda, A., Steptoe, A. et al. The independent association between salivary alpha-amylase activity and arterial stiffness in Japanese men and women: the Toon Health Study. Hypertens Res 45, 1249–1262 (2022). https://doi.org/10.1038/s41440-022-00963-8

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