Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Differences in longitudinal associations of cardiovascular risk factors with arterial stiffness and pressure wave reflection in middle-aged Japanese men

Hypertension Research volume 44, pages 98–106 (2021)Cite this article

Abstract

The present prospective observational study was conducted to examine the differences in longitudinal associations of the conventional risk factors for cardiovascular disease (CVD) with arterial stiffness and with abnormal pressure wave reflection using repeated measurement data. In 4016 healthy middle-aged (43 ± 9 years) Japanese men without CVD at baseline, the conventional risk factors for CVD, brachial–ankle pulse wave velocity (brachial–ankle PWV) and radial augmentation index (rAI) were measured annually over a 9-year period. Mixed-model linear regression analysis demonstrated a significant independent positive longitudinal association of the mean blood pressure with both the brachial–ankle PWV (estimate = 5.51, standard error = 0.30, P < 0.01) and the rAI (estimate = 0.19, standard error = 0.02, P < 0.01). On the other hand, the serum levels of glycohemoglobin, low-density lipoprotein cholesterol and triglycerides showed longitudinal associations only with the brachial–ankle PWV and not the rAI. In addition, while the radial AI was found to show a significant longitudinal association with the brachial–ankle PWV, the inverse association was not significant. In conclusion, the conventional risk factors for CVD showed heterogeneous longitudinal associations with arterial stiffness and/or abnormal pressure wave reflection. Elevated blood pressure showed independent longitudinal associations with both arterial stiffness (macrovascular damage) and abnormal pressure wave reflection, suggesting that BP is also longitudinally associated, at least in part, with microvascular damage. On the other hand, abnormal glucose metabolism and dyslipidemia showed independent longitudinal associations with only arterial stiffness (macrovascular damage).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ohkuma T, Ninomiya T, Tomiyama H, Kario K, Hoshide S, Kita Y, et al. Brachial-ankle pulse wave velocity and the risk prediction of cardiovascular disease: an individual participant data meta-analysis. Hypertension. 2017;69:1045–52. https://doi.org/10.1161/HYPERTENSIONAHA.117.09097.

    Article  CAS  PubMed  Google Scholar 

  2. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol. 2014;63:636–46. https://doi.org/10.1016/j.jacc.2013.09.063.

    Article  PubMed  Google Scholar 

  3. Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31:1865–71. https://doi.org/10.1093/eurheartj/ehq024.

    Article  PubMed  Google Scholar 

  4. O’Rourke MF, Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol. 2007;50:1–13. https://doi.org/10.1016/j.jacc.2006.12.050.

    Article  PubMed  Google Scholar 

  5. Tomiyama H, Komatsu S, Shiina K, Matsumoto C, Kimura K, Fujii M, et al. Effect of wave reflection and arterial stiffness on the risk of development of hypertension in Japanese men. J Am Heart Assoc. 2018;7:e008175. https://doi.org/10.1161/JAHA.117.008175.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Climie RED, Picone DS, Blackwood S, Keel SE, Qasem A, Rattigan S, et al. Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes. Eur J Appl Physiol. 2018;118:2455–63. https://doi.org/10.1007/s00421-018-3972-2.

    Article  CAS  PubMed  Google Scholar 

  7. Tomiyama H, Yamashina A. Non-invasive vascular function tests: their pathophysiological background and clinical application. Circ J. 2010;74:24–33. https://doi.org/10.1253/circj.cj-09-0534.

    Article  PubMed  Google Scholar 

  8. Rizzoni D, De Ciuceis C, Salvetti M, Paini A, Rossini C, Agabiti-Rosei C, et al. Interactions between macro- and micro-circulation: are they relevant? High Blood Press Cardiovasc Prev. 2015;22:119–28. https://doi.org/10.1007/s40292-015-0086-3.

    Article  CAS  PubMed  Google Scholar 

  9. Climie RE, van Sloten TT, Bruno RM, Taddei S, Empana JP, Stehouwer CDA, et al. Macrovasculature and microvasculature at the crossroads between type 2 diabetes mellitus and hypertension. Hypertension. 2019;73:1138–49. https://doi.org/10.1161/HYPERTENSIONAHA.118.11769.

    Article  CAS  PubMed  Google Scholar 

  10. Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015;116:1007–21. https://doi.org/10.1161/CIRCRESAHA.116.303596.

    Article  CAS  PubMed  Google Scholar 

  11. Milwidsky A, Kivity S, Kopel E, Klempfner R, Berkovitch A, Segev S, et al. Time dependent changes in high density lipoprotein cholesterol and cardiovascular risk. Int J Cardiol. 2014;173:295–9. https://doi.org/10.1016/j.ijcard.2014.03.022.

    Article  PubMed  Google Scholar 

  12. Bangalore S, Fayyad R, DeMicco DA, Colhoun HM, Waters DD. Body weight variability and cardiovascular outcomes in patients with type 2 diabetes mellitus. Circ Cardiovasc Qual Outcomes. 2018;11:e004724. https://doi.org/10.1161/CIRCOUTCOMES.118.004724.

    Article  PubMed  Google Scholar 

  13. Yang J, Zaitlen NA, Goddard ME, Visscher PM, Price AL. Advantages and pitfalls in the application of mixed-model association methods. Nat Genet. 2014;46:100–6. https://doi.org/10.1038/ng.2876.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Tomiyama H, Shiina K, Matsumoto-Nakano C, Ninomiya T, Komatsu S, Kimura K, et al. The contribution of inflammation to the development of hypertension mediated by increased arterial stiffness. J Am Heart Assoc. 2017;30:e005729. https://doi.org/10.1161/JAHA.117.005729.

    Article  Google Scholar 

  15. Tomiyama H, Shiina K, Vlachopoulos C, Iwasaki Y, Matsumoto C, Kimura K, et al. Involvement of arterial stiffness and inflammation in hyperuricemia-related development of hypertension. Hypertension. 2018;72:739–45. https://doi.org/10.1161/HYPERTENSIONAHA.118.11390.

    Article  CAS  PubMed  Google Scholar 

  16. Smulyan H, Lieber A, Safar ME. Hypertension, diabetes type II, and their association: role of arterial stiffness. Am J Hypertens. 2016;29:5–13. https://doi.org/10.1093/ajh/hpv107.

    Article  CAS  PubMed  Google Scholar 

  17. Cypienė A, Dadonienė J, Rugienė R, Ryliškytė L, Kovaitė M, Petrulionienė Z, et al. The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus. Medicina. 2010;46:522–30. https://doi.org/10.3390/medicina46080075.

    Article  PubMed  Google Scholar 

  18. Safar ME, Boudier HS. Vascular development, pulse pressure, and the mechanisms of hypertension. Hypertension. 2005;46:205–9. https://doi.org/10.1161/01.HYP.0000167992.80876.26.

    Article  CAS  PubMed  Google Scholar 

  19. Tomiyama H, Yamazaki M, Sagawa Y, Teraoka K, Shirota T, Miyawaki Y, et al. Synergistic effect of smoking and blood pressure on augmentation index in men, but not in women. Hypertens Res. 2009;32:122–6. https://doi.org/10.1038/hr.2008.20.

    Article  PubMed  Google Scholar 

  20. Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res. 2002;25:359–64. https://doi.org/10.1291/hypres.25.359.

    Article  PubMed  Google Scholar 

  21. Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus, Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1:212–28. https://doi.org/10.1111/j.2040-1124.2010.00074.x.

    Article  Google Scholar 

  22. Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S. Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. Am J Kidney Dis. 2010;56:32–8. https://doi.org/10.1053/j.ajkd.2010.02.344.

    Article  PubMed  Google Scholar 

  23. Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension. 2009;54:1328–36. https://doi.org/10.1161/HYPERTENSIONAHA.109.137653.

    Article  CAS  PubMed  Google Scholar 

  24. Scuteri A, Morrell CH, Orrù M, Strait JB, Tarasov KV, Ferreli LA, et al. Longitudinal perspective on the conundrum of central arterial stiffness, blood pressure, and aging. Hypertension. 2014;64:1219–27. https://doi.org/10.1161/HYPERTENSIONAHA.114.04127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. McEniery CM, Spratt M, Munnery M, Yarnell J, Lowe GD, Rumley A, et al. An analysis of prospective risk factors for aortic stiffness in men: 20-year follow-up from the Caerphilly prospective study. Hypertension. 2010;56:36–43. https://doi.org/10.1161/HYPERTENSIONAHA.110.150896.

    Article  CAS  PubMed  Google Scholar 

  26. Mitchell GF, Conlin PR, Dunlap ME, Lacourcière Y, Arnold JM, Ogilvie RI, et al. Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension. 2008;51:105–11. https://doi.org/10.1161/HYPERTENSIONAHA.107.099721.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang M, Bai Y, Ye P, Luo L, Xiao W, Wu H, et al. Type 2 diabetes is associated with increased pulse wave velocity measured at different sites of the arterial system but not augmentation index in a Chinese population. Clin Cardiol. 2011;34:622–7. https://doi.org/10.1002/clc.20956.

    Article  PubMed  PubMed Central  Google Scholar 

  28. McEniery CM, Wilkinson IB, Johansen NB, Witte DR, Singh-Manoux A, Kivimaki M, et al. Nondiabetic glucometabolic status and progression of aortic stiffness: the Whitehall II study. Diabetes Care. 2017;40:599–606. https://doi.org/10.2337/dc16-1773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhao X, Wang H, Bo L, Zhao H, Li L, Zhou Y. Serum lipid level and lifestyles are associated with carotid femoral pulse wave velocity among adults: 4.4-year prospectively longitudinal follow-up of a clinical trial. Clin Exp Hypertens. 2018;40:487–94. https://doi.org/10.1080/10641963.2017.1384486.

    Article  PubMed  Google Scholar 

  30. Wilkinson IB, Prasad K, Hall IR, Thomas A, MacCallum H, Webb DJ, et al. Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia. J Am Coll Cardiol. 2002;39:1005–11. https://doi.org/10.1016/S0735-1097(02)01723-0.

    Article  PubMed  Google Scholar 

  31. Wang X, Ye P, Cao R, Yang X, Xiao W, Zhang Y, et al. Triglycerides are a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. Lipids Health Dis. 2016;15:97. https://doi.org/10.1186/s12944-016-0266-8.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Otsuka T, Kawada T, Ibuki C, Kusama Y. Radial arterial wave reflection is associated with the MEGA risk prediction score, an indicator of coronary heart disease risk, in middle-aged men with mild to moderate hypercholesterolemia. J Atheroscler Thromb. 2010;17:688–94. https://doi.org/10.5551/jat.2949.

    Article  PubMed  Google Scholar 

  33. Wilkinson I, Cockcroft JR. Cholesterol, lipids and arterial stiffness. Adv Cardiol. 2007;44:261–77. https://doi.org/10.1159/000096747.

    Article  CAS  PubMed  Google Scholar 

  34. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 2015;238:370–9. https://doi.org/10.1016/j.atherosclerosis.2014.12.023.

    Article  CAS  PubMed  Google Scholar 

  35. Badhwar S, Chandran DS, Jaryal AK, Narang R, Deepak KK. Regional arterial stiffness in central and peripheral arteries is differentially related to endothelial dysfunction assessed by brachial flow-mediated dilation in metabolic syndrome. Diab Vasc Dis Res. 2018;15:106–13. https://doi.org/10.1177/1479164117748840.

    Article  CAS  PubMed  Google Scholar 

  36. Wen J, Huang Y, Lu Y, Yuan H. Associations of non-high-density lipoprotein cholesterol, triglycerides and the total cholesterol/HDL-c ratio with arterial stiffness independent of low-density lipoprotein cholesterol in a Chinese population. Hypertens Res. 2019;42:1223–30. https://doi.org/10.1038/s41440-019-0251-5.

    Article  CAS  PubMed  Google Scholar 

  37. Roes SD, Alizadeh Dehnavi R, Westenberg JJ, Lamb HJ, Mertens BJ, Tamsma JT, et al. Assessment of aortic pulse wave velocity and cardiac diastolic function in subjects with and without the metabolic syndrome: HDL cholesterol is independently associated with cardiovascular function. Diabetes Care. 2008;31:1442–4. https://doi.org/10.2337/dc08-0055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adams SP, Tiellet N, Alaeiilkhchi N, Wright JM. Cerivastatin for lowering lipids. Cochrane Database Syst Rev. 2020;1:CD012501. https://doi.org/10.1002/14651858.CD012501.pub2.

    Article  PubMed  Google Scholar 

  39. Upala S, Wirunsawanya K, Jaruvongvanich V, Sanguankeo A. Effects of statin therapy on arterial stiffness: a systematic review and meta-analysis of randomized controlled trial. Int J Cardiol. 2017;227:338–41. https://doi.org/10.1016/j.ijcard.2016.11.073.

    Article  PubMed  Google Scholar 

  40. Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI, et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol. 2009;20:2044–53. https://doi.org/10.1681/ASN.2009010074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tomiyama H, Tanaka H, Hashimoto H, Matsumoto C, Odaira M, Yamada J, et al. Arterial stiffness and declines in individuals with normal renal function/early chronic kidney disease. Atherosclerosis. 2010;212:345–50. https://doi.org/10.1016/j.atherosclerosis.2010.05.033.

    Article  CAS  PubMed  Google Scholar 

  42. Tomiyama H, Matsumoto C, Shiina K, Yamashina A, Brachial-Ankle PWV. Current status and future directions as a useful marker in the management of cardiovascular disease and/or cardiovascular risk factors. J Atheroscler Thromb. 2016;23:128–46. https://doi.org/10.5551/jat.32979.

    Article  CAS  PubMed  Google Scholar 

  43. Huang J, Chen Z, Yuan J, Zhang C, Chen H, Wu W, et al. Association between body mass index (BMI) and brachial-ankle pulse wave velocity (bapwv) in males with hypertension: a community-based cross-section study in North China. Med Sci Monit. 2019;25:5241–57. https://doi.org/10.12659/MSM.914881.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hernandez-Martinez A, Martinez-Rosales E, Alcaraz-Ibañez M, Soriano-Maldonado A, Artero EG. Influence of body composition on arterial stiffness in middle-aged adults: healthy UAL cross-sectional study. Medicina. 2019;55:E334. https://doi.org/10.3390/medicina55070334.

    Article  PubMed  Google Scholar 

  45. Maple-Brown LJ, Piers LS, O’Rourke MF, Celermajer DS, O’Dea K. Central obesity is associated with reduced peripheral wave reflection in Indigenous Australians irrespective of diabetes status. J Hypertens. 2007;23:1403–7. https://doi.org/10.1097/01.hjh.0000173524.80802.5a.

    Article  Google Scholar 

  46. Tang B, Luo F, Zhao J, Ma J, Tan I, Butlin M, et al. Relationship between body mass index and arterial stiffness in a health assessment Chinese population. Medicine. 2020;99:e18793. https://doi.org/10.1097/MD.0000000000018793.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Tomiyama H, Hashimoto H, Tanaka H, Matsumoto C, Odaira M, Yamada J, et al. Continuous smoking and progression of arterial stiffening: a prospective study. J Am Coll Cardiol. 2010;55:1979–87. https://doi.org/10.1016/j.jacc.2009.12.042.

    Article  CAS  PubMed  Google Scholar 

  48. Wilkinson IB, Mäki-Petäjä KM, Mitchell GF. Uses of arterial stiffness in clinical practice. Arterioscler Thromb Vasc Biol. 2020;40:1063–7. https://doi.org/10.1161/ATVBAHA.120.313130.

Download references

Acknowledgements

This study was supported by Omron Health Care Company (Kyoto, Japan), Asahi Calpis Wellness Company (Tokyo, Japan) and Teijin Pharma Company (Tokyo, Japan), which awarded funds to Professors Akira Yamashina and Hirofumi Tomiyama.

Author information

Authors and Affiliations

  1. Department of Cardiology and Division of Preemptive Medicine for Vascular Damage, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku City, Tokyo, 160-0023, Japan

    Masatsune Fujii, Hirofumi Tomiyama, Hiroki Nakano, Yoichi Iwasaki, Chisa Matsumoto, Kazuki Shiina, Akira Yamashina & Taishiro Chikamori

Authors
  1. Masatsune Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hirofumi Tomiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroki Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoichi Iwasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chisa Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuki Shiina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Yamashina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Taishiro Chikamori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hirofumi Tomiyama.

Ethics declarations

Conflict of interest

The sponsor (Omron Health Care Company) assisted in the data formatting (i.e., the data of the brachial–ankle PWV stored in the hard disc of the equipment used for measurement of the brachial–ankle PWV were transferred to an Excel file). Other than this, the company played no role in the design or conduct of the study, i.e., in the data collection, management, analysis or interpretation of the data or in the preparation, review or approval of the paper. The authors have no other disclosures to make.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujii, M., Tomiyama, H., Nakano, H. et al. Differences in longitudinal associations of cardiovascular risk factors with arterial stiffness and pressure wave reflection in middle-aged Japanese men. Hypertens Res 44, 98–106 (2021). https://doi.org/10.1038/s41440-020-0523-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-020-0523-0

Keywords

This article is cited by

Search

Advanced search

Quick links