Skip to main content
SpringerLink
Log in

The Role of the Brain in Neurogenic Prehypertension

  • Chapter
  • First Online:
Prehypertension and Cardiometabolic Syndrome

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

  • 652 Accesses

Abstract

The association between blood pressure (BP) levels and increased risk for cardiovascular (CV) events is a continuum. The negative impact of elevated BP on patient outcomes is evident in the prehypertensive state which includes both subjects with normal (120–129/80–84 mmHg) and high-normal (130–139/85–89 mmHg) BP. The underlying pathophysiology linking prehypertension to poor CV prognosis is complex and not entirely understood. Available evidence indicates that particular consideration should be given to subjects in the upper end of BP values (stage 2 prehypertension), in whom neurohumoral activation with heightened activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), along with the presence of CV risk factors, play a causative role in BP initiation, adverse complications, and transition to hypertension. Therapy with candesartan found an absolute reduction in new-onset hypertension in subjects with high-normal BP, possibly through an inhibition of relevant neurohormonal pathways acting on the brain RAS and sympathetic outflow. However, until randomized clinical trials prove benefits of antihypertensive therapy on hard CV endpoints in stage 2 prehypertension, intensive lifestyle interventions should be widely implemented to prevent the incidence of hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Julius S, Schork MA. Borderline hypertension—a critical review. J Chronic Dis. 1971;23:723–54.

    Article  CAS  PubMed  Google Scholar 

  2. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997;157:2413–46.

    Google Scholar 

  3. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105–87.

    Article  CAS  PubMed  Google Scholar 

  4. Yamada Y, Miyajima E, Tochikubo O, Matsukawa T, Shionoiri H, Ishii M, Kaneko Y. Impaired baroreflex changes in muscle sympathetic nerve activity in adolescents who have a family history of essential hypertension. J Hypertens. 1988;6:S525–8.

    Article  CAS  Google Scholar 

  5. Davis JT, Rao F, Naqshbandi D, Fung MM, Zhang K, Schork AJ, Nievergelt CM, Ziegler MG, O’Connor DT. Autonomic and hemodynamic origins of prehypertension: central role of heredity. J Am Coll Cardiol. 2012;59:2206–16.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhang M, Ardile K, Wacholder S, Weich R, Chanock S, O’Brien TR. Genetic variations in CC chemokine receptors and hypertension. Am J Hypertens. 2006;19:67–72.

    Article  CAS  PubMed  Google Scholar 

  7. Delles C, McBride MW, Graham D, Padmanabhan S, Dominiczak AF. Genetics of hypertension: from experimental animals to humans. Biochim Biophys Acta. 2010;1802:1299–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hottenga JJ, Whitfield JB, de Geus EJ, Booms DI, Martin NG. Heritability and stability of resting blood pressure in Australia twins. Twin Res Hum Genet. 2006;9:205–9.

    Article  PubMed  Google Scholar 

  9. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.

    Article  PubMed  Google Scholar 

  10. Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y. Is prehypertension a risk factor for cardiovascular diseases? Stroke. 2005;36(9):1859–63.

    Article  PubMed  Google Scholar 

  11. Ninomiya T, Kubo M, Doi Y, Yonemoto K, Tanizaki Y, Tsuruya K, et al. Prehypertension increases the risk for renal arteriosclerosis in autopsies: the Hisayama Study. J Am Soc Nephrol. 2007;18(7):2135–42.

    Article  PubMed  Google Scholar 

  12. Wikstrom AK, Gunnarsdottir J, Nelander M, Simic M, Stephansson O, Cnattingius S. Prehypertension in pregnancy and risks of small for gestational age infant and stillbirth. Hypertension. 2016;67(3):640–6.

    Article  PubMed  Google Scholar 

  13. Greenlund KJ, Croft JB, Mensah GA. Prevalence of heart disease and stroke risk factors in persons with prehypertension in the United States, 1999–2000. Arch Intern Med. 2004;164(19):2113–8.

    Article  PubMed  Google Scholar 

  14. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354(16):1685–97.

    Article  CAS  PubMed  Google Scholar 

  15. Egan BM, Julius S. Prehypertension: risk stratification and management considerations. Curr Hypertens Rep. 2008;10(5):359–66.

    Article  PubMed  Google Scholar 

  16. Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003;42(4):474–80.

    Article  CAS  PubMed  Google Scholar 

  17. Hering D, Kara T, Kucharska W, Somers VK, Narkiewicz K. Longitudinal tracking of muscle sympathetic nerve activity and its relationship with blood pressure in subjects with prehypertension. Blood Press. 2016;25(3):184–92.

    Article  PubMed  Google Scholar 

  18. Seravalle G, Lonati L, Buzzi S, Cairo M, Quarti trevano F, Dell’Oro R, Facchetti R, Mancia G, Grassi G. Sympathetic nerve traffic and baroreflex function in optimal, normal, and high-normal blood pressure states. J Hypertens. 2015;33:1411–7.

    Article  CAS  PubMed  Google Scholar 

  19. Julius S, Feldstein CA. Prehypertension: definitions, clinical significance and therapeutic approaches—to treat or not to treat? In: Berbari E, Mancia G, editors. Special issue on hypertension: Springer-Verlag; 2012. p. 3–12.

    Google Scholar 

  20. Smith PA, Graham LN, Mackintosh AF, Stoker JB, Mary DA. Sympathetic neural mechanisms in white-coat hypertension. J Am Coll Cardiol. 2002;40:126–33.

    Article  PubMed  Google Scholar 

  21. Grassi G, Seravalle G, Trevano FQ, Dell’Oro R, Bolla GB, Cuspidi C, et al. Neurogenic abnormalities in masked hypertension. Hypertension. 2007;50:537–42.

    Article  CAS  PubMed  Google Scholar 

  22. Fagard RH, Stolarz K, Kuznestova T, Seidlerova J, Tikhonoff V, Grodzicki T, et al. Sympathetic activity assessed by power spectral analysis of heart rate variability in white-coat, masked and sustained hypertension versus true normotension. J Hypertens. 2007;25:2280–5.

    Article  CAS  PubMed  Google Scholar 

  23. Pal GK, Adithan C, Dutta TK, Amudharaj D, Pravati P, Nandan PG, et al. Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population. Clin Exp Hypertens. 2011;33:478–83.

    Article  CAS  PubMed  Google Scholar 

  24. Grassi G, Esler M. How to assess sympathetic activity in humnans. J Hypertens. 1999;17:719–34.

    Article  CAS  PubMed  Google Scholar 

  25. Grassi G, Vailati S, Bertinieri G, Seravalle G, Stella ML, Dell’Oro R, Mancia G. Heart rate as a marker of sympathetic activity. J Hypertens. 1998;16:1635–9.

    Article  CAS  PubMed  Google Scholar 

  26. Flaa A, Eide IK, Kjeldsen SE, Rostrup M. Sympathoadrenal stress reactivity is a predictor of future blood pressure: an 18-year follow-up study. Hypertension. 2008;52:336–41.

    Article  CAS  PubMed  Google Scholar 

  27. Wilkinson DJ, Thompson JM, Lambert GW, Jennings GL, Schwarz RG, Jefferys D, Turner AG, Esler MD. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch Gen Psychiatry. 1998;55:511–20.

    Article  CAS  PubMed  Google Scholar 

  28. Vasan R, Larson M, Leip E, Kannel W, Levy D. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet. 2001;358:1682–6.

    Article  CAS  PubMed  Google Scholar 

  29. Ishikawa Y, Ishikawa J, Ishikawa S, Kayaba K, Nakamura Y, Shimada K, et al. Prevalence and determinants of prehypertension in a Japanese general population: the Jichi Medical School Cohort Study. Hypertens Res. 2008;31:1323–30.

    Article  PubMed  Google Scholar 

  30. Tirosh A, Afek A, Rudich A, Percik R, Gordon B, Ayalon N, et al. Progression of normotensive adolescents to hypertensive adults. A study of 26980 teenagers. Hypertension. 2010;56:203–9.

    Article  CAS  PubMed  Google Scholar 

  31. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischemic heart disease. Lancet. 1989;2:577–80.

    Article  CAS  PubMed  Google Scholar 

  32. Heijzer-veen MG, Finken MJ, Nauta J, Dekker FW, Hille ET, Frolich M, et al. Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in the Netherlands. Pediatrics. 2005;116:725–31.

    Article  Google Scholar 

  33. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannattasio C, Brunani A, Cavagnini F, Mancia G. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25:560–3.

    Article  CAS  PubMed  Google Scholar 

  34. Lund-Johansen P. Hemodynamic in early essential hypertension. Acta Med Scand. 1967;482:1–105.

    Google Scholar 

  35. Frolich ED, Kozul VJ, Tarazi RC, Dustan HP. Physiological comparison of labile and essential hypertension. Circ Res. 1970;26:55–69.

    Google Scholar 

  36. Julius S, Pascual A, Sannerstedt R, Mitchell C. Relationship between cardiac output and peripheral resistance in borderline hypertension. Circulation. 1971;43:382–90.

    Article  CAS  PubMed  Google Scholar 

  37. Takeshita A, Tanaka S, Kuroiwa A, Nakamura M. Reduced baroreceptor sensitivity in borderline hepertension. Circulation. 1975;51:738–42.

    Article  CAS  PubMed  Google Scholar 

  38. Eckberg DL. Carotid baroreflex function in young men with borderline blood pressure elevation. Circulation. 1979;59:632–6.

    Article  CAS  PubMed  Google Scholar 

  39. Levy RL, White PD, Stroud WD, Hillman CC. Transient tachycardia: prognostic significance alone and in association with transient hypertension. JAMA. 1945;129:585–8.

    Article  Google Scholar 

  40. Trimarco B, Volpe M, Ricciardelli B, et al. Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension. Hypertension. 1983;5:584–90.

    Article  CAS  PubMed  Google Scholar 

  41. Julius S, Randall OS, Esler MD, Kashima T, Ellis CN, Bennett J. Altered cardiac responsiveness and regulation in the normal cardiac output type of borderline hypertension. Circ Res. 1975;36–37(Suppl. I):I-199–207.

    Article  Google Scholar 

  42. Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982;62:347–503.

    Article  CAS  PubMed  Google Scholar 

  43. Mulvany MJ, Hansen PK, Aalkjaer C. Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layer. Circ Res. 1978;43:854–64.

    Article  CAS  PubMed  Google Scholar 

  44. Schiffrin EL. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens. 2004;17:1192–200.

    Article  CAS  PubMed  Google Scholar 

  45. Izzard AS, Rizzoni D, Agabiti Rosei E, Heagerty AM. Small artery structure and hypertension: adaptative changes and target organ damage. J Hypertens. 2005;23:247–50.

    Article  CAS  PubMed  Google Scholar 

  46. Grassi G, Buzzi S, Dell’Oro R, Mineo C, Dimitriadis K, Seravalle G, Lonati L, Cuspidi C. Structural alterations of the retinal microcirculation in the “prehypertensive” high-normal blood pressure state. Curr Pharmaceutical Des. 2013;19:2375–81.

    Article  CAS  Google Scholar 

  47. Psaty BM, Arnold AM, Olson J, et al. Association between levels of blood pressure and measures of subclinical disease multiethnic study of atherosclerosis. Am J Hypertens. 2006;19:1110–7.

    Article  PubMed  Google Scholar 

  48. Haffner SM, Miettinen H, Gaskill SP, Stern MP. Metabolic precursors of hypertension. The San Antonio Heart Study. Arch Intern Med. 1996;156:1994–2001.

    Article  CAS  PubMed  Google Scholar 

  49. Bo S, Gambino R, Gentile L, et al. High-normal blood pressure is associated with a cluster of cardiovascular and metabolic risk factors: a population-based study. J Hypertens. 2009;27:102–8.

    Article  CAS  PubMed  Google Scholar 

  50. Mancia G, Luscher TF, Shepherd JT, Noll G, Grassi G. Cardiovascular regulation: basic considerations. In: Willerson JT, Cohn JN, Wellens HJJ, Holmes Jr DR, editors. Cardiovascular medicine. London: Springer-Verlag; 2007. p. 1525–36.

    Chapter  Google Scholar 

  51. O’Rourke MF. Vascular impedance in studies of arterial and cardiac function. Physiol Rev. 1982;62:570–623.

    Article  PubMed  Google Scholar 

  52. Jennings JR, Zanstra Y. Is the brain the essential in hypertension? Neuroimage. 2009;47(3):914–21.

    Article  PubMed  Google Scholar 

  53. Jennings JR, Heim AF. From brain to behavior: hypertension’s modulation of cognition and affect. Int J Hypertens. 2012;2012:701385.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Gianaros PJ, Jennings JR, Sheu LK, Derbyshire SW, Matthews KA. Heightened functional neural activation to psychological stress covaries with exaggerated blood pressure reactivity. Hypertension. 2007;49(1):134–40.

    Article  CAS  PubMed  Google Scholar 

  55. Gianaros PJ, Sheu LK, Remo AM, Christie IC, Crtichley HD, Wang J. Heightened resting neural activity predicts exaggerated stressor-evoked blood pressure reactivity. Hypertension. 2009;53(5):819–25.

    Article  CAS  PubMed  Google Scholar 

  56. Ryan JP, Sheu LK, Gianaros PJ. Resting state functional connectivity within the cingulate cortex jointly predicts agreeableness and stressor-evoked cardiovascular reactivity. Neuroimage. 2011;55(1):363–70.

    Article  PubMed  Google Scholar 

  57. Naumczyk P, Sabisz A, Witkowska M, Graff B, Jodzio K, Gasecki D, et al. Compensatory functional reorganization may precede hypertension-related brain damage and cognitive decline: a functional magnetic resonance imaging study. J Hypertens. 2017;35(6):1252–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Conflict of Interest disclosures: none.

Each author does not have any personal or financial relationships that have any potential to inappropriately influence the manuscript; there are no financial or other potential conflicts of interest including involvement with any organization with a direct financial, intellectual, or other interest in the manuscript. In addition there are no grants and sources of financial support related to the topic of the manuscript.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing.

Author information

Authors and Affiliations

  1. Cardiology Department, Istituto Auxologico Italiano IRCCS Ospedale San Luca, Milano, Italy

    Gino Seravalle

  2. Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland

    Dagmara Hering & Krzysztof Narkiewicz

  3. Clinica Medica, Department of Medicine and Surgery, University Milano-Bicocca, Milan, Italy

    Guido Grassi

  4. IRCCS Multimedica, Milan, Italy

    Guido Grassi

Authors
  1. Gino Seravalle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dagmara Hering
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guido Grassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krzysztof Narkiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Krzysztof Narkiewicz .

Editor information

Editors and Affiliations

  1. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Reuven Zimlichman

  2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Stevo Julius

  3. Emeritus Professor of Medicine, University of Milano-Bicocca, Milan, Italy

    Giuseppe Mancia

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Seravalle, G., Hering, D., Grassi, G., Narkiewicz, K. (2019). The Role of the Brain in Neurogenic Prehypertension. In: Zimlichman, R., Julius, S., Mancia, G. (eds) Prehypertension and Cardiometabolic Syndrome. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-75310-2_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-75310-2_25

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-75309-6

  • Online ISBN: 978-3-319-75310-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation