Advertisement

Orthostatic hypotension and health outcomes: an umbrella review of observational studies

  • Pinar SoysalEmail author
  • Nicola Veronese
  • Lee Smith
  • Gabriel Torbahn
  • Sarah E. Jackson
  • Lin Yang
  • Andrea Ungar
  • Giulia Rivasi
  • Martina Rafanelli
  • Mirko Petrovic
  • Stefania Maggi
  • Ahmet Turan Isik
  • Jacopo Demurtas
  • The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS)
Research Paper

Key summary points

Aim

To investigate potential relationships between orthostatic hypotension (OH) and negative health outcomes and mortality, through an umbrella review with integrated meta-analyses.

Findings

Orthostatic hypotension is significantly associated with several negative outcomes in older people, but a suggestive evidence is available only for higher risk of coronary heart disease congestive heart failure, stroke, falls dementia, and all-cause mortality.

Message

Orthostatic hypotension seems to be significantly associated with several negative health outcomes in older people, even if only associations with coronary heart disease, congestive heart failure, stroke, falls, dementia, and all-cause mortality are supported by suggestive evidence.

Abstract

Purpose

Orthostatic hypotension (OH) is associated with older age and many negative clinical outcomes in geriatric practice. We aimed to capture the breadth of outcomes that have been associated with the presence of OH and systematically assess the quality, strength and credibility of these associations using an umbrella review with integrated meta-analyses.

Methods

We systematically searched several major databases from their commencements through to 16th May 2019 for meta-analyses of observational studies of OH and any health-related outcome. We used these metrics to categorize the strength of evidence of significant outcomes (p < 0.05) from class I (convincing) to class IV (weak), according to the pre-established criteria.

Results

From 975 abstracts, seven meta-analyses of 12 outcomes were included. For each outcome, the median number of studies was four, and the median number of participants was 46,493, with a median of 3630 incident cases. There was suggestive (class III) evidence that OH was associated with significantly higher risk of coronary heart disease (HR = 1.32, 95% CI 1.12–1.56), stroke (HR = 1.22, 95% CI 1.08–1.38), congestive heart failure (HR = 1.30, 95% CI 1.09–1.55), all-cause mortality (RR = 1.50, 95% CI 1.24–1.81), falls (OR = 1.84, 95% CI 1.39–2.44), and dementia (HR = 1.22, 95% CI 1.11–1.35).

Conclusion

The current evidence base indicates that OH is significantly associated with a range of adverse cardiovascular, cognitive, and mortality outcomes in older people, although the strength of this evidence remains only suggestive. Further research in larger samples and with lower risk of bias is required to build a fuller picture of the impact of OH on health.

Keywords

Orthostatic hypotension Umbrella review Meta-analysis Mortality Fall Heart failure Heart disease Stroke 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

It was not requested being a revision of already published literature. This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

No patients were included in this review.

Sponsor’s role

None.

Supplementary material

41999_2019_239_MOESM1_ESM.docx (38 kb)
Supplementary material 1 (DOCX 37 kb)

References

  1. 1.
    American Autonomic Society, The American Academy of Neurology (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 46:1470CrossRefGoogle Scholar
  2. 2.
    Low PA (2008) Prevalence of orthostatic hypotension. Clin Auton Res 18:8–13CrossRefGoogle Scholar
  3. 3.
    Soysal P, Aydin AE, Okudur SK, Isik AT (2016) When should orthostatic blood pressure changes be evaluated in elderly: 1st, 3rd or 5th minute? Arch Gerontol Geriatr 65:199–203CrossRefGoogle Scholar
  4. 4.
    Aydin AE, Soysal P, Isik AT (2017) Which is preferable for orthostatic hypotension diagnosis in older adults: active standing test or head-up tilt table test? Clin Interv Aging 12:207CrossRefGoogle Scholar
  5. 5.
    Low PA, Tomalia VA (2015) Orthostatic hypotension: mechanisms, causes, management. J Clin Neurol 11:220–226CrossRefGoogle Scholar
  6. 6.
    Verwoert GC, Mattace-Raso FU, Hofman A, Heeringa J, Stricker BH, Breteler MM, Witteman JC (2008) Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. J Am Geriatr Soc 56:1816–1820CrossRefGoogle Scholar
  7. 7.
    Atkins D, Hanusa B, Sefcik T, Kapoor W (1991) Syncope and orthostatic hypotension. Am J Med 91:179–185CrossRefGoogle Scholar
  8. 8.
    Yap PLK, Niti M, Yap KB, Ng TP (2008) Orthostatic hypotension, hypotension and cognitive status: early comorbid markers of primary dementia? Dement Geriatr Cogn Disord 26:239CrossRefGoogle Scholar
  9. 9.
    Gupta V, Lipsitz LA (2007) Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 120:841–847CrossRefGoogle Scholar
  10. 10.
    Schneider L, Sloane RB, Staples FR, Bender M (1986) Pretreatment orthostatic hypotension as a predictor of response to nortriptyline in geriatric depression. J Clin Psychopharmacol 6:172–176CrossRefGoogle Scholar
  11. 11.
    Chen L, Xu Y, Chen X, Lee W-J, Chen L-K (2019) Association between orthostatic hypotension and frailty in hospitalized older patients: a geriatric syndrome more than a cardiovascular condition. J Nutr Health Aging 23:318–322CrossRefGoogle Scholar
  12. 12.
    Ioannidis JP (2009) Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses. CMAJ 181:488–493CrossRefGoogle Scholar
  13. 13.
    Whiting P, Savović J, Higgins JP, Caldwell DM, Reeves BC, Shea B, Davies P, Kleijnen J, Churchill R (2016) ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol 69:225–234CrossRefGoogle Scholar
  14. 14.
    Avelino-Silva TJ, Jaluul O (2017) Malnutrition in hospitalized older patients: management strategies to improve patient care and clinical outcomes. Int J Gerontol 11:56–61CrossRefGoogle Scholar
  15. 15.
    Stroud M, Duncan H, Nightingale J (2003) Guidelines for enteral feeding in adult hospital patients. Gut 52:vii1CrossRefGoogle Scholar
  16. 16.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefGoogle Scholar
  17. 17.
    Veronese N, Notarnicola M, Osella A et al (2018) Menopause does not affect fatty liver severity in women: a population study in a Mediterranean area. Endocr Metabol Immune Disord Drug Targets 18(5):513–521.  https://doi.org/10.2174/1871530318666180423101755 CrossRefGoogle Scholar
  18. 18.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634CrossRefGoogle Scholar
  19. 19.
    Carvalho AF, Kohler CA, Brunoni AR, Miskowiak KW, Herrmann N, Lanctot KL, Hyphantis TN, Quevedo J, Fernandes BS, Berk M (2016) Bias in peripheral depression biomarkers. Psychother Psychosom 85:81–90CrossRefGoogle Scholar
  20. 20.
    Ioannidis JP, Trikalinos TA (2007) An exploratory test for an excess of significant findings. Clin Trials 4:245–253CrossRefGoogle Scholar
  21. 21.
    Aromataris E, Fernandez R, Godfrey CM, Holly C, Khalil H, Tungpunkom P (2015) Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. Int J Evid Based Health Care 13:132–140CrossRefGoogle Scholar
  22. 22.
    Belbasis L, Savvidou MD, Kanu C, Evangelou E, Tzoulaki I (2016) Birth weight in relation to health and disease in later life: an umbrella review of systematic reviews and meta-analyses. BMC Med 14:147CrossRefGoogle Scholar
  23. 23.
    Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JP (2016) Environmental risk factors and Parkinson’s disease: an umbrella review of meta-analyses. Parkinsonism Relat Disord 23:1–9CrossRefGoogle Scholar
  24. 24.
    Dinu M, Pagliai G, Casini A, Sofi F (2017) Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomized trials. Nutr Metabol Cardiovasc Dis 27:e21Google Scholar
  25. 25.
    Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, Martin-Hirsch P, Tsilidis KK (2017) Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ 356:j477CrossRefGoogle Scholar
  26. 26.
    Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis KK, Ioannidis PA, Campbell H, Theodoratou E (2017) Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ 357:j2376CrossRefGoogle Scholar
  27. 27.
    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035CrossRefGoogle Scholar
  28. 28.
    Veronese N, Solmi M, Caruso MG, Giannelli G, Osella AR, Evangelou E, Maggi S, Fontana L, Stubbs B, Tzoulaki I (2018) Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses. Am J Clin Nutr 107:436–444CrossRefGoogle Scholar
  29. 29.
    Machado MO, Veronese N, Sanches M et al (2018) The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med 16:112CrossRefGoogle Scholar
  30. 30.
    Veronese N, Demurtas J, Celotto S et al (2018) Is chocolate consumption associated with health outcomes? An umbrella review of systematic reviews and meta-analyses. Clin Nutr 38(3):1101–1108CrossRefGoogle Scholar
  31. 31.
    Veronese N, Demurtas J, Pesolillo G et al (2019) Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr.  https://doi.org/10.1007/s00394-019-01905-w Google Scholar
  32. 32.
    Köhler CA, Evangelou E, Stubbs B et al (2018) Mapping risk factors for depression across the lifespan: an umbrella review of evidence from meta-analyses and Mendelian randomization studies. J Psychiatr Res 103:189–207CrossRefGoogle Scholar
  33. 33.
    Smith L, Luchini C, Demurtas J et al (2019) Telomere length and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational studies. Ageing Res Rev 51:1–10CrossRefGoogle Scholar
  34. 34.
    Iseli R, Nguyen VTV, Sharmin S, Reijnierse EM, Lim WK, Maier AB (2019) Orthostatic hypotension and cognition in older adults: a systematic review and meta-analysis. Exp Gerontol 120:40–49CrossRefGoogle Scholar
  35. 35.
    Min M, Shi T, Sun C, Liang M, Zhang Y, Wu Y, Sun Y (2018) The association between orthostatic hypotension and dementia: a meta-analysis of prospective cohort studies. Int J Geriatr Psychiatry 33:1541–1547CrossRefGoogle Scholar
  36. 36.
    Mol A, Hoang PTSB, Sharmin S, Reijnierse EM, van Wezel RJ, Meskers CG, Maier AB (2018) Orthostatic hypotension and falls in older adults: a systematic review and meta-analysis. J Am Med Dir Assoc 20(5):589–597CrossRefGoogle Scholar
  37. 37.
    Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, Zimarino M, De Caterina R (2015) Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies. Eur Heart J 36:1609–1617CrossRefGoogle Scholar
  38. 38.
    Xin W, Lin Z, Li X (2013) Orthostatic hypotension and the risk of congestive heart failure: a meta-analysis of prospective cohort studies. PLoS One 8:e63169CrossRefGoogle Scholar
  39. 39.
    Xin W, Lin Z, Mi S (2014) Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies. Heart 100:406–413CrossRefGoogle Scholar
  40. 40.
    Xin W, Mi S, Lin Z, Wang H, Wei W (2016) Orthostatic hypotension and the risk of incidental cardiovascular diseases: a meta-analysis of prospective cohort studies. Prev Med 85:90–97CrossRefGoogle Scholar
  41. 41.
    Smit AA, Halliwill JR, Low PA, Wieling W (1999) Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol 519(Pt 1):1–10CrossRefGoogle Scholar
  42. 42.
    Mattace-Raso FU, van der Cammen TJ, Knetsch AM, van den Meiracker AH, Schalekamp MA, Hofman A, Witteman JC (2006) Arterial stiffness as the candidate underlying mechanism for postural blood pressure changes and orthostatic hypotension in older adults: the Rotterdam study. J Hypertens 24:339–344CrossRefGoogle Scholar
  43. 43.
    Fedorowski A, Ostling G, Persson M, Struck J, Engstrom G, Nilsson PM, Hedblad B, Melander O (2012) Orthostatic blood pressure response, carotid intima-media thickness, and plasma fibrinogen in older nondiabetic adults. J Hypertens 30:522–529CrossRefGoogle Scholar
  44. 44.
    Fan XH, Wang Y, Sun K, Zhang W, Wang H, Wu H, Zhang H, Zhou X, Hui R (2010) Disorders of orthostatic blood pressure response are associated with cardiovascular disease and target organ damage in hypertensive patients. Am J Hypertens 23:829–837CrossRefGoogle Scholar
  45. 45.
    Pepersack T, Gilles C, Petrovic M, Spinnewine A, Baeyens H, Beyer I, Boland B, Dalleur O, De Lepeleire J, Even-Adin D, Van Nes MC, Samalea-Suarez A, Somers A, Working Group Clinical Pharmacology, Pharmacotherapy and Pharmaceutical Care, Belgian Society for Gerontology and Geriatrics (2013) Prevalence of orthostatic hypotension and relationship with drug use amongst older patients. Acta Clin Belg 68:107–112CrossRefGoogle Scholar
  46. 46.
    Mager DR (2012) Orthostatic hypotension: pathophysiology, problems, and prevention. Home Healthc Nurse 30:525–530CrossRefGoogle Scholar
  47. 47.
    Aoki M, Tanaka K, Wakaoka T, Kuze B, Hayashi H, Mizuta K, Ito Y (2013) The association between impaired perception of verticality and cerebral white matter lesions in the elderly patients with orthostatic hypotension. J Vestib Res 23:85–93Google Scholar
  48. 48.
    Humm AM, Bostock H, Troller R, Z’Graggen WJ (2011) Muscle ischaemia in patients with orthostatic hypotension assessed by velocity recovery cycles. J Neurol Neurosurg Psychiatry 82:1394–1398CrossRefGoogle Scholar
  49. 49.
    Chisholm P, Anpalahan M (2017) Orthostatic hypotension: pathophysiology, assessment, treatment and the paradox of supine hypertension. Intern Med J 47:370–379CrossRefGoogle Scholar
  50. 50.
    Elmstahl S, Rosen I (1997) Postural hypotension and EEG variables predict cognitive decline: results from a 5-year follow-up of healthy elderly women. Dement Geriatr Cogn Disord 8:180–187CrossRefGoogle Scholar
  51. 51.
    Toyry JP, Kuikka JT, Lansimies EA (1997) Regional cerebral perfusion in cardiovascular reflex syncope. Eur J Nucl Med 24:215–218CrossRefGoogle Scholar
  52. 52.
    Brown WR, Thore CR (2011) Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol 37:56–74CrossRefGoogle Scholar
  53. 53.
    Liu H, Zhang J (2012) Cerebral hypoperfusion and cognitive impairment: the pathogenic role of vascular oxidative stress. Int J Neurosci 122:494–499CrossRefGoogle Scholar
  54. 54.
    Foster-Dingley JC, Moonen JEF, de Ruijter W, van der Mast RC, van der Grond J (2018) Orthostatic hypotension in older persons is not associated with cognitive functioning, features of cerebral damage or cerebral blood flow. J Hypertens 36:1201–1206CrossRefGoogle Scholar
  55. 55.
    Flachenecker P, Wolf A, Krauser M, Hartung H-P, Reiners K (1999) Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance. J Neurol 246:578–586CrossRefGoogle Scholar
  56. 56.
    Lim SY, Lang AE (2010) The nonmotor symptoms of Parkinson’s disease: an overview. Mov Disord 25(Suppl 1):S123–S130CrossRefGoogle Scholar
  57. 57.
    Gaspar L, Kruzliak P, Komornikova A et al (2016) Orthostatic hypotension in diabetic patients: 10-year follow-up study. J Diabetes Complicat 30:67–71CrossRefGoogle Scholar
  58. 58.
    Isik AT, Kocyigit SE, Smith L, Aydin AE, Soysal P (2019) A comparison of the prevalence of orthostatic hypotension between older patients with Alzheimer’s disease, Lewy body dementia, and without dementia. Exp Gerontol 124:110628.  https://doi.org/10.1016/j.exger.2019.06.001 CrossRefGoogle Scholar
  59. 59.
    Xin W, Lin Z, Mi S (2014) Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies. Heart 100:406–413CrossRefGoogle Scholar
  60. 60.
    Robertson D (2008) The pathophysiology and diagnosis of orthostatic hypotension. Clin Auton Res 18(Suppl 1):2–7CrossRefGoogle Scholar
  61. 61.
    Sabbah HN (2012) Baroreflex activation for the treatment of heart failure. Curr Cardiol Rep 14:326–333CrossRefGoogle Scholar
  62. 62.
    Schwartz PJ, La Rovere MT (1998) ATRAMI: a mark in the quest for the prognostic value of autonomic markers. Autonomic tone and reflexes after myocardial infarction. Eur Heart J 19:1593–1595CrossRefGoogle Scholar
  63. 63.
    La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (autonomic tone and reflexes after myocardial infarction) investigators. Lancet 351:478–484CrossRefGoogle Scholar
  64. 64.
    Ioannidis JP (2016) The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q 94:485–514CrossRefGoogle Scholar

Copyright information

© European Geriatric Medicine Society 2019

Authors and Affiliations

  • Pinar Soysal
    • 1
    Email author
  • Nicola Veronese
    • 2
  • Lee Smith
    • 3
  • Gabriel Torbahn
    • 4
  • Sarah E. Jackson
    • 5
  • Lin Yang
    • 6
  • Andrea Ungar
    • 7
  • Giulia Rivasi
    • 7
  • Martina Rafanelli
    • 7
  • Mirko Petrovic
    • 8
  • Stefania Maggi
    • 2
  • Ahmet Turan Isik
    • 9
  • Jacopo Demurtas
    • 10
  • The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS)
  1. 1.Department of Geriatric Medicine, Faculty of MedicineBezmialem Vakif UniversityIstanbulTurkey
  2. 2.National Research CouncilNeuroscience InstitutePaduaItaly
  3. 3.The Cambridge Centre for Sport and Exercise SciencesAnglia Ruskin UniversityCambridgeUK
  4. 4.Institute for Biomedicine of AgingFriedrich Alexander University Erlangen-NürnbergNurembergGermany
  5. 5.Department of Behavioural Science and HealthUniversity College LondonLondonUK
  6. 6.Department of Cancer Epidemiology and Prevention ResearchAlbert Health ServicesCalgaryCanada
  7. 7.Department of GeriatricsAzienda Ospedaliero-Universitaria Careggi and University of FlorenceFlorenceItaly
  8. 8.Department of Internal Medicine, Section of GeriatricsGhent UniversityGhentBelgium
  9. 9.Unit for Aging Brain and Dementia, Department of Geriatric Medicine, Faculty of MedicineDokuz Eylul UniversityIzmirTurkey
  10. 10.Primary Care Department Azienda USL Toscana Sud EstGrossetoItaly

Personalised recommendations