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Hypertension, cardiovascular disease, and nocturia: a systematic review of the pathophysiological mechanisms

Hypertension Research volume 44, pages 733–739 (2021)Cite this article

Abstract

Nocturia significantly impairs quality of life, especially in the elderly population, and urinary retention is a main target of treatment for urologists. In addition to nocturia, cardiovascular diseases are common in the elderly population, and a systematic review showed that hypertension and heart failure are often associated with nocturia. One possible pathogenic mechanism underlying the development of hypertension is an increase in blood pressure due to excessive salt intake in people with high-salt sensitivity. From Guyton’s natriuretic curve, we can infer that salt-sensitive hypertensive patients who consume too much salt do not excrete salt during the daytime and are forced to excrete salt at night, resulting in increased urine production and nocturia. In patients with heart failure, the nocturnal supine position leads to an increase in central fluid volume due to an increase in venous return from the periphery, and the secretion of natriuretic peptide is stimulated by the stretching of the atria and ventricles. Thus, natriuresis due to hypertension and hydrodiuresis due to heart failure may cause nocturia, which can effectively be treated by the administration of thiazide diuretics and loop diuretics in the morning, respectively. Because cardiovascular diseases, such as hypertension and heart failure, can cause nocturia and because the treatment methods differ depending on the cause, it is necessary to pay close attention to nocturia in the management of lifestyle-related diseases, such as cardiovascular disease.

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References

  1. Hisamatsu T, Segawa H, Kadota A, Ohkubo T, Arima H, Miura K. Epidemiology of hypertension in Japan: beyond the new 2019 Japanese guidelines. Hypertens Res. 2020;43:1344–51.

    Article  CAS  PubMed  Google Scholar 

  2. Tsuchihashi T, Ishimitsu T, Ando K, Kusaka M, Ichihara A, Miura K, et al. JSH statement: Tokyo declaration promoting salt reduction by the Japanese Society of Hypertension-the JSH Tokyo declaration. Hypertens Res. 2020;43:1133–4.

    Article  PubMed  Google Scholar 

  3. Yoshimura R, Yamamoto R, Shinzawa M, Tomi R, Ozaki S, Fujii Y, et al. Frequency of alcohol drinking modifies the association between salt intake and albuminuria: a 1-year observational study. Hypertens Res. 2020;43:1249–56.

    Article  CAS  PubMed  Google Scholar 

  4. Kogure M, Nakaya N, Hirata T, Tsuchiya N, Nakamura T, Narita A, et al. Sodium/potassium ratio change was associated with blood pressure change: possibility of population approach for sodium/potassium ratio reduction in health checkup. Hypertens Res. 2021;44:225–31.

    Article  CAS  PubMed  Google Scholar 

  5. The Japanese Continence Society and the Japanese Urological Association. 2nd edition of the Clinical Guidelines for Nocturia. Tokyo, Japan: RichHill Medical; 2020.

  6. Bower WF, Whishaw DM, Khan F. Nocturia as a marker of poor health: causal associations to inform care. Neurourol Urodyn. 2017;36:697–705.

    Article  PubMed  Google Scholar 

  7. Rahman SN, Cao DJ, Monaghan TF, Flores VX, Vaysblat M, Moy MW, et al. Phenotyping the association between nocturia and hypertension: a systematic review and meta-analysis. J Urol. 2020. https://doi.org/10.1097/JU.0000000000001433. Online ahead of print.

  8. Chow PM, Liu SP, Chuang YC, Lee KS, Yoo TK, Liao L, et al. The prevalence and risk factors of nocturia in China, South Korea, and Taiwan: results from a cross-sectional, population-based study. World J Urol. 2018;36:1853–62.

    Article  CAS  PubMed  Google Scholar 

  9. Yokoyama O, Nishizawa O, Homma Y, Takeda M, Gotoh M, Kakizaki H, et al. Nocturnal polyuria and hypertension in patients with lifestyle related diseases and overactive bladder. J Urol. 2017;197:423–31.

    Article  PubMed  Google Scholar 

  10. Matsuo T, Miyata Y, Sakai H. Daily salt intake is an independent risk factor for pollakiuria and nocturia. Int J Urol. 2017;24:384–9.

    Article  CAS  PubMed  Google Scholar 

  11. Kim SY, Bang W, Kim MS, Park B, Kim JH, Choi HG. Analysis of the prevalence and factors associated with nocturia in adult Korean men. Sci Rep. 2017;7:41714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Obayashi K, Saeki K, Negoro H, Kurumatani N. Nocturia increases the incidence of depressive symptoms: a longitudinal study of the HEIJO-KYO cohort. BJU Int. 2017;120:280–5.

    Article  PubMed  Google Scholar 

  13. Wang Y, Hu H, Xu K, Zhang X, Wang X, Na Y, et al. Prevalence, risk factors, and symptom bother of nocturia: a population-based survey in China. World J Urol. 2015;33:677–83.

    Article  CAS  PubMed  Google Scholar 

  14. Wen L, Wen YB, Wang ZM, Wen JG, Li ZZ, Shang XP, et al. Risk factors of nocturia (two or more voids per night) in Chinese people older than 40 years. Neurourol Urodyn. 2015;34:566–70.

    Article  PubMed  Google Scholar 

  15. Parthasarathy S, Fitzgerald M, Goodwin JL, Unruh M, Guerra S, Quan SFNocturia. sleep-disordered breathing, and cardiovascular morbidity in a community-based cohort. PLoS One. 2012;7:e30969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Burgio KL, Johnson TM 2nd, Goode PS, Markland AD, Richter HE, Roth DL, et al. Prevalence and correlates of nocturia in community-dwelling older adults. J Am Geriatr Soc. 2010;58:861–6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bing MH, Moller LA, Jennum P, Mortensen S, Lose G. Nocturia and associated morbidity in a Danish population of men and women aged 60-80 years. BJU Int. 2008;102:808–14.

    Article  PubMed  Google Scholar 

  18. Sugaya K, Nishijima S, Oda M, Owan T, Miyazato M, Ogawa Y. Biochemical and body composition analysis of nocturia in the elderly. Neurourol Urodyn. 2008;27:205–11.

    Article  CAS  PubMed  Google Scholar 

  19. Hsieh CH, Chen HY, Hsu CS, Chang ST, Chiang CD. Risk factors for nocturia in Taiwanese women aged 20-59 years. Taiwan J Obstet Gynecol. 2007;46:166–70.

    Article  PubMed  Google Scholar 

  20. Johnson TM 2nd, Sattin RW, Parmelee P, Fultz NH, Ouslander JG. Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults. J Am Geriatr Soc. 2005;53:1011–6.

    Article  PubMed  Google Scholar 

  21. Rembratt A, Norgaard JP, Andersson KE. Nocturia and associated morbidity in a community-dwelling elderly population. BJU Int. 2003;92:726–30.

    Article  CAS  PubMed  Google Scholar 

  22. Matsumoto T, Tabara Y, Murase K, Setoh K, Kawaguchi T, Nagashima S, et al. Nocturia and increase in nocturnal blood pressure: the Nagahama study. J Hypertens. 2018;36:2185–92.

    Article  CAS  PubMed  Google Scholar 

  23. Gourova LW, van de Beek C, Spigt MG, Nieman FH, van Kerrebroeck PE. Predictive factors for nocturia in elderly men: a cross-sectional study in 21 general practices. BJU Int. 2006;97:528–32.

    Article  PubMed  Google Scholar 

  24. Liu HY, Chung MS, Wang HJ, Liu RT, Chuang YC. Nocturia indicates a poor health status and increases mortality in male patients with type 2 diabetes mellitus. Int Urol Nephrol. 2016;48:1209–14.

    Article  CAS  PubMed  Google Scholar 

  25. Destors M, Tamisier R, Sapene M, Grillet Y, Baguet JP, Richard P, et al. Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients. Sleep Med. 2015;16:652–8.

    Article  PubMed  Google Scholar 

  26. Miyazato M, Tana T, Higa A, Wakugami K, Tokashiki T, Sakima H, et al. A questionnaire survey to assess lower urinary tract symptoms in patients with chronic stroke. Neurourol Urodyn. 2017;36:1890–5.

    Article  PubMed  Google Scholar 

  27. Lim J, Bhoo-Pathy N, Sothilingam S, Malek R, Sundram M, Tan GH, et al. Cardiovascular risk factors and ethnicity are independent factors associated with lower urinary tract symptoms. PLoS One. 2015;10:e0130820.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lightner DJ, Krambeck AE, Jacobson DJ, McGree ME, Jacobsen SJ, Lieber MM, et al. Nocturia is associated with an increased risk of coronary heart disease and death. BJU Int. 2012;110:848–53.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Guyton AC. Renal function curve –a key to understanding the pathogenesis of hypertension. Hypertension 1987;10:1–6.

    Article  CAS  PubMed  Google Scholar 

  30. Uzu T, Ishikawa K, Fujii T, Nakamura S, Inenaga T, Kimura G. Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. 1997;96:1859–62.

    Article  CAS  PubMed  Google Scholar 

  31. Mizuno M, Fukuda M, Miura T, Wakamatsu T, Naito T, Sato R, et al. Morning hypertension in chronic kidney disease is sustained type, but not surge type. Blood Press Monit. 2012;17:20–3.

    Article  PubMed  Google Scholar 

  32. Uzu T, Kimura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. 1999;100:1635–8.

    Article  CAS  PubMed  Google Scholar 

  33. Cho MC, Ku JH, Paick JS. Alpha-blocker plus diuretic combination therapy as second-line treatment for nocturia in men with LUTS: a pilot study. Urology 2009;73:549–53.

    Article  PubMed  Google Scholar 

  34. Mueller C, Frana B, Rodriguez D, Laule-Kilian K, Perruchoud AP. Emergency diagnosis of congestive heart failure: impact of signs and symptoms. Can J Cardiol. 2005;21:921–4.

    PubMed  Google Scholar 

  35. Redeker NS, Adams L, Berkowitz R, Blank L, Freudenberger R, Gilbert M, et al. Rapoport D. Nocturia, sleep and daytime function in stable heart failure. J Card Fail. 2012;18:569–75.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kaszuba E, Wagner B, Odeberg H, Halling A. Using NT-proBNP to detect chronic heart failure in elderly patients with chronic obstructive pulmonary disease. ISRN Fam Med. 2013;2013:273864.

    Google Scholar 

  37. Siniorakis E, Kotsanis A, Kanderakis S, Exarchos S, Kapiris I. Nocturia in males with heart failure: prostatic edema and circadian neurohormonal rhythm. Int J Cardiol. 2008;123:361–3.

    Article  PubMed  Google Scholar 

  38. Shiga T, Suzuki A, Haruta S, Mori F, Ota Y, Yagi M, et al. Clinical characteristics of hospitalized heart failure patients with preserved, mid-range, and reduced ejection fractions in Japan. ESC Heart Fail. 2019;6:475–86.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kawasoe S, Maruguchi Y, Kajiya S, Uenomachi H, Miyata M, Kawasoe M, et al. Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes. BMC Pharm Toxicol. 2017;18:23.

    Article  Google Scholar 

  40. The Japanese Circulation Society and the Japanese Heart Failure Society. Guidelines for diagnosis and treatment of acute and chronic heart failure. The Japanese Circulation Society and the Japanese Heart Failure Society: Tokyo, Japan; 2017. in Japanese

  41. Bursztyn M, Jacob J, Stessman J. Usefulness of nocturia as a mortality risk factor for coronary heart disease among persons born in 1920 or 1921. Am J Cardiol. 2006;98:1311–5.

    Article  PubMed  Google Scholar 

  42. Tikkinen KA, Auvinen A, Johnson TM 2nd, Weiss JP, Keränen T, Tiitinen A, et al. A systematic evaluation of factors associated with nocturia-the population-based FINNO study. Am J Epidemiol. 2009;170:361–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Geovanini GR, Libby P. Atherosclerosis and inflammation: overview and updates. Clin Sci. 2018;132:1243–52.

    Article  CAS  Google Scholar 

  44. De Nunzio C, Aronson W, Freedland SJ, Giovannucci E, Parsons JK. The correlation between metabolic syndrome and prostatic diseases. Eur Urol. 2012;61:560–70.

    Article  PubMed  Google Scholar 

  45. Peyronnet B, Mironska E, Chapple C, Cardozo L, Oelke M, Dmochowski R, et al. A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment. Eur Urol. 2019;75:988–1000.

    Article  PubMed  Google Scholar 

  46. Ohishi M, Yamamoto K, Rakugi H. Angiotensin (1-7) and other angiotensin peptides. Curr Pharm Des. 2013;19:3060–4.

    Article  CAS  PubMed  Google Scholar 

  47. Ohishi M. Hypertension with diabetes mellitus: physiology and pathology. Hypertens Res. 2018;41:389–93.

    Article  PubMed  Google Scholar 

  48. Ohishi M, Ueda M, Rakugi H, Naruko T, Kojima A, Okamura A, et al. Enhanced expression of angiotensin-converting enzyme is associated with progression of coronary atherosclerosis in humans. J Hypertens. 1997;15:1295–302.

    Article  CAS  PubMed  Google Scholar 

  49. Ohishi M, Dusting GJ, Fennessy PA, Mendelsohn FAO, Li XC, Zhuo JL. Increased expression and co-localization of ACE, angiotensin II AT1 receptors and inducible nitric oxide synthase in atherosclerotic human coronary arteries. Int J Physiol Pathophysiol Pharm. 2010;2:111–24.

    CAS  Google Scholar 

  50. Nassis L, Frauman AG, Ohishi M, Zhuo JL, Casley DJ, Johnston CI, et al. Localization of angiotensin-converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia. J Pathol. 2001;195:571–9.

    Article  CAS  PubMed  Google Scholar 

  51. Dinh DT, Frauman AG, Somers GR, Ohishi M, Zhuo J, Casley DJ, et al. Evidence for activation of the renin–angiotensin system in the human prostate: increased angiotensin II and reduced AT1 receptor expression in prostatic hyperplasia. J Pathol. 2002;196:213–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Medicine and Hypertension, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Mitsuru Ohishi, Takuro Kubozono, Koji Higuchi & Yuichi Akasaki

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  1. Mitsuru Ohishi
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Correspondence to Mitsuru Ohishi.

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Ohishi, M., Kubozono, T., Higuchi, K. et al. Hypertension, cardiovascular disease, and nocturia: a systematic review of the pathophysiological mechanisms. Hypertens Res 44, 733–739 (2021). https://doi.org/10.1038/s41440-021-00634-0

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Keywords

  • Nocturnal hypertension
  • Nocturia
  • Nocturnal polyuria
  • Water diuresis
  • Natriuresis

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