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  • Review Article
  • Special Issue: Current evidence and perspectives for hypertension management in Asia
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Systemic hemodynamic atherothrombotic syndrome: from hypothesis to evidence

Hypertension Research volume 47, pages 579–585 (2024)Cite this article

Abstract

Hypertension is a risk factor for cardiovascular disease (CVD). However, the association between blood pressure (BP) and CVD events has been based on mean BP alone. BP variability (BPV) is associated with increased organ damage and CVD events independently or beyond average home BP. To explain this association, we propose the systemic hemodynamic atherothrombotic syndrome (SHATS) hypothesis. The SHATS hypothesis indicates that hemodynamic stress increases vascular disease and vice versa, leading to a vicious cycle of the association between hemodynamic stress and a vascular disease; this association provides not only the risk but also the trigger for CVD events. The evidences of SHATS were gradually accumulating. We showed arterial stiffness synergistically amplified the association between hemodynamic stress and cardiac overload / CVD events in patients with at least one CVD risk factor.

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References

  1. Imano H, Kitamura A, Sato S, Kiyama M, Ohira T, Yamagishi K, et al. Trends for blood pressure and its contribution to stroke incidence in the middle-aged Japanese population: the Circulatory Risk in Communities Study (CIRCS). Stroke 2009;40:1571–77.

    Article  PubMed  Google Scholar 

  2. Fujiyoshi A, Ohkubo T, Miura K, Murakami Y, Nagasawa SY, Okamura T, et al. Observational Cohorts in Japan (EPOCH-JAPAN) Research Group. Blood pressure categories and long-term risk of cardiovascular disease according to age group in Japanese men and women. Hypertens Res. 2012;35:947–53.

    Article  PubMed  Google Scholar 

  3. Takashima N, Ohkubo T, Miura K, Okamura T, Murakami Y, Fujiyoshi A, et al. NIPPON DATA80 Research Group. Long-term risk of BP values above normal for cardiovascular mortality: a 24-year observation of Japanese aged 30 to 92 years. J Hypertens. 2012;30:2299–306.

    Article  CAS  PubMed  Google Scholar 

  4. Ikeda A, Iso H, Yamagishi K, Inoue M, Tsugane S. Blood pressure and the risk of stroke, cardiovascular disease, and all-cause mortality among Japanese: the JPHC Study. Am J Hypertens. 2009;22:273–80.

    Article  PubMed  Google Scholar 

  5. Arima H, Tanizaki Y, Yonemoto K, Doi Y, Ninomiya T, Hata J, et al. Impact of blood pressure levels on different types of stroke: the Hisayama study. J Hypertens. 2009;27:2437–43.

    Article  CAS  PubMed  Google Scholar 

  6. Lawes CM, Rodgers A, Bennett DA, Parag V, Suh I, Ueshima H, et al. Asia Pacific Cohort Studies Collaboration. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens. 2003;21:707–16.

    Article  CAS  PubMed  Google Scholar 

  7. Lida M, Ueda K, Okayama A, Kodama K, Sawai K, Shibata S, et al. Nippon Data 80 Research Group. Impact of elevated blood pressure on mortality from all causes, cardiovascular diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly selected population from Japanese – Nippon data 80. J Hum Hypertens. 2003;17:851–7.

    Article  PubMed  Google Scholar 

  8. Tanizaki Y, Kiyohara Y, Kato I, Iwamoto H, Nakayama K, Shinohara N, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study. Stroke 2000;31:2616–22.

    Article  CAS  PubMed  Google Scholar 

  9. Asayama K, Satoh M, Murakami Y, Ohkubo T, Nagasawa SY, Tsuji I, et al. Evidence for cardiovascular prevention from observational cohorts in Japan (EPOCH-JAPAN) Research Group. Cardiovascular risk with and without antihypertensive drug treatment in the Japanese general population: participant-level meta-analysis. Hypertension 2014;63:1189–97.

    Article  CAS  PubMed  Google Scholar 

  10. Ward AM, Takahashi O, Stevens R, Heneghan C. Home measurement of blood pressure and cardiovascular disease: Systematic review and meta-analysis of prospective studies. J Hypertens. 2012;30:449–56.

    Article  CAS  PubMed  Google Scholar 

  11. Noguchi Y, Asayama K, Staessen JA, Inaba M, Ohkubo T, Hosaka M, et al. HOMED-BP study group. Predictive power of home blood pressure and clinic blood pressure in hypertensive patients with impaired glucose metabolism and diabetes. J Hypertens. 2013;31:1593–602.

    Article  CAS  PubMed  Google Scholar 

  12. Ohkubo T, Imai Y, Tsuji I, Nagai K, Kato J, Kikuchi N, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens. 1998;16:971–5.

    Article  CAS  PubMed  Google Scholar 

  13. Sega R, Facchetti R, Bombelli M, Cesana G, Corrao G, Grassi G, et al. Prognostic value of ambulatory and home bloodpressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation 2005;111:1777–83.

    Article  PubMed  Google Scholar 

  14. Shimada K, Kario K, Kushiro T, Teramukai S, Zenimura N, Ishikawa Y, et al. Prognostic significance of on-treatment home and clinic blood pressure for predicting cardiovascular events in hypertensive patients in the HONEST study. J Hypertens. 2016;34:1520–7.

    Article  CAS  PubMed  Google Scholar 

  15. Kario K, Saito I, Kushiro T, Teramukai S, Tomono Y, Okuda Y, et al. Morning Home Blood Pressure Is a Strong Predictor of Coronary Artery Disease: The HONEST Study. J Am Coll Cardiol. 2016;67:1519–27.

    Article  PubMed  Google Scholar 

  16. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127–e248.

    Article  PubMed  Google Scholar 

  17. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041.

    Article  CAS  PubMed  Google Scholar 

  18. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

    Article  PubMed  Google Scholar 

  19. Johansson JK, Niiranen TJ, Puukka PJ, Jula AM. Prognostic value of the variability in home-measured blood pressure and heart rate: The Finn-Home Study. Hypertension 2012;59:212–8.

    Article  CAS  PubMed  Google Scholar 

  20. Kikuya M, Ohkubo T, Metoki H, Asayama K, Hara A, Obara T, et al. Day-by-day variability of blood pressure and heart rate at home as a novel predictor of prognosis: The Ohasama study. Hypertension 2008;52:1045–50.

    Article  CAS  PubMed  Google Scholar 

  21. Hoshide S, Yano Y, Mizuno H, Kanegae H, Kario K. Day-by-day variability of home blood pressure and incident cardiovascular disease in clinical practice: The J-HOP Study (Japan Morning Surge-Home Blood Pressure). Hypertension 2018;71:177–84.

    Article  CAS  PubMed  Google Scholar 

  22. Hoshide S, Yano Y, Haimoto H, Yamagiwa K, Uchiba K, Nagasaka S, et al. J-HOP Study Group. Morning and evening home blood pressure and risks of incident stroke and coronary artery disease in the Japanese general practice population: The Japan Morning Surge-Home Blood Pressure Study. Hypertension 2016;68:54–61.

    Article  CAS  PubMed  Google Scholar 

  23. Asayama K, Kikuya M, Schutte R, Thijs L, Hosaka M, Satoh M, et al. Home blood pressure variability as cardiovascular risk factor in the population of Ohasama. Hypertension 2013;61:61–9.

    Article  CAS  PubMed  Google Scholar 

  24. Ishiyama Y, Hoshide S, Mizuno H, Kario K. Constipation‐induced pressor effects as triggers for cardiovascular events. J Clin Hypertens (Greenwich). 2019;21:421–5.

    Article  PubMed  Google Scholar 

  25. Kario K. Systemic hemodynamic atherothrombotic syndrome: A blind spot in the current management of hypertension. J Clin Hypertens (Greenwich). 2015;17:328–31.

    Article  PubMed  Google Scholar 

  26. Kario K. Systemic hemodynamic atherothrombotic syndrome (SHATS): Diagnosis and severity assessment score. J Clin Hypertens (Greenwich). 2019;21:1011–5.

    Article  PubMed  Google Scholar 

  27. Kario K, Chirinos JA, Townsend RR, Weber MA, Scuteri A, Avolio A, et al. Systemic hemodynamic atherothrombotic syndrome (SHATS) - coupling vascular disease and blood pressure variability: proposed concept from pulse of Asia. Prog Cardiovasc Dis. 2020;63:22–32.

    Article  PubMed  Google Scholar 

  28. Belz GG. Elastic properties and windkessel function of the human aorta. Cardiovasc Drugs Ther. 1995;9:73–83.

    Article  CAS  PubMed  Google Scholar 

  29. Pucci G, Battista F, Anastasio F, Schillaci G. Morning pressor surge, blood pressure variability, and arterial stiffness in essential hypertension. J Hypertens. 2017;35:272–8.

    Article  CAS  PubMed  Google Scholar 

  30. Mancia G, Parati G, Pomidossi G, Casadei R, Rienzo MD, Zanchetti A. Arterial baroreflexes and blood pressure and heart rate variabilities in humans. Hypertension 1986;8:147–53.

    Article  CAS  PubMed  Google Scholar 

  31. Monahan KD, Dinenno FA, Seals DR, Clevenger CM, Desouza CA, Tanaka H. Age-associated changes in cardiovagal baroreflex sensitivity are related to central arterial compliance. Am J Physiol Heart Circ Physiol. 2001;281:H284–9.

    Article  CAS  PubMed  Google Scholar 

  32. Tomiyama H, Matsumoto C, Kimura K, Odaira M, Shiina K, Yamashina A. Pathophysiological contribution of vascular function to baroreflex regulation in hypertension. Circ J. 2014;78:1414–9.

    Article  CAS  PubMed  Google Scholar 

  33. Mattace-Raso FU, van den Meiracker AH, Bos WJ, van der Cammen TJ, Westerhof BE, Elias-Smale S, et al. Arterial stiffness, cardiovagal baroreflex sensitivity and postural blood pressure changes in older adults: the Rotterdam Study. J Hypertens. 2007;25:1421–6.

    Article  CAS  PubMed  Google Scholar 

  34. Robinson TG, Dawson SL, Eames PJ, Panerai RB, Potter JF. Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke. Stroke 2003;34:705–12.

    Article  PubMed  Google Scholar 

  35. Hadase M, Azuma A, Zen K, Asada S, Kawasaki T, Kamitani T, et al. Very low frequency power of heart rate variability is a powerful predictor of clinical prognosis in patients with congestive heart failure. Circ J. 2004;68:343–7.

    Article  PubMed  Google Scholar 

  36. Matsui Y, Eguchi K, Shibasaki S, Ishikawa J, Hoshide S, Shimada K, et al. Impact of arterial stiffness reduction on urinary albumin excretion during antihypertensive treatment: the Japan morning Surge-1 study. J Hypertens. 2010;28:1752–60.

    Article  CAS  PubMed  Google Scholar 

  37. Satoh M, Hosaka M, Asayama K, Kikuya M, Inoue R, Metoki H, et al. Association between N-terminal pro B-type natriuretic peptide and day-to-day blood pressure and heart rate variability in a general population: the Ohasama study. J Hypertens. 2015;33:1536–41.

    Article  CAS  PubMed  Google Scholar 

  38. Nagai M, Hoshide S, Nishikawa M, Masahisa S, Kario K. Visit-to-visit blood pressure variability in the elderly: associations with cognitive impairment and carotid artery remodeling. Atherosclerosis 2014;233:19–26.

    Article  CAS  PubMed  Google Scholar 

  39. Ishiyama Y, Hoshide S, Kanegae H, Kario K. Increased Arterial Stiffness Amplifies the Association Between Home Blood Pressure Variability and Cardiac Overload: The J-HOP Study. Hypertension 2020;75:1600–6.

    Article  CAS  PubMed  Google Scholar 

  40. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236–41.

    Article  CAS  PubMed  Google Scholar 

  41. Takashima N, Turin TC, Matsui K, Rumana N, Nakamura Y, Kadota A, et al. The relationship of brachial-ankle pulse wave velocity to future cardiovascular disease events in the general Japanese population: The Takashima Study. J Hum Hypertens. 2014;28:323–7.

    Article  CAS  PubMed  Google Scholar 

  42. Fujiwara T, Hoshide S, Kanegae H, Kario K. Clinical Impact of the Maximum Mean Value of Home Blood Pressure on Cardiovascular Outcomes: A Novel Indicator of Home Blood Pressure Variability. Hypertension 2021;78:840–50.

    Article  CAS  PubMed  Google Scholar 

  43. Ishiyama Y, Hoshide S, Kanegae H, Kario K. Impact of home blood pressure variability on cardiovascular outcome in patients with arterial stiffness: Results of the J-HOP study. J Clin Hypertens (Greenwich). 2021;23:1529–37.

    Article  CAS  PubMed  Google Scholar 

  44. Hoshide S, Tomitani N, Kario K. Maximum ambulatory daytime blood pressure and risk of stroke in individuals with higher ambulatory arterial stiffness index: the JAMP study. Hypertens Res. 2023;46:84–90.

    Article  PubMed  Google Scholar 

  45. Scuteri A, Rovella V, Alunni Fegatelli D, Tesauro M, Gabriele M, Di Daniele N, et al. An operational definition of SHATS (Systemic Hemodynamic Atherosclerotic Syndrome): Role of arterial stiffness and blood pressure variability in elderly hypertensive subjects. Int J Cardiol. 2018;263:132–7.

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  1. Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Tochigi, Japan

    Yusuke Ishiyama, Satoshi Hoshide & Kazuomi Kario

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  1. Yusuke Ishiyama
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Correspondence to Kazuomi Kario.

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KK reports funded research/joint research expenses from Omron Healthcare, Fukuda Denshi, A&D; lecture fees from A&D and Omron Healthare, outside the submitted work. Other authors report no potential conflicts of interest in relation to this article.

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Ishiyama, Y., Hoshide, S. & Kario, K. Systemic hemodynamic atherothrombotic syndrome: from hypothesis to evidence. Hypertens Res 47, 579–585 (2024). https://doi.org/10.1038/s41440-023-01459-9

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