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Impact of hypertension on cerebral microvascular structure in CPAP-treated obstructive sleep apnoea patients: a diffusion magnetic resonance imaging study

  • Functional Neuroradiology
  • Published:
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Abstract

Purpose

Obstructive sleep apnoea (OSA) is a highly prevalent sleep-related breathing disorder associated with hypertension, impaired peripheral vascular function and an increased risk of stroke. Evidence suggests that abnormalities of the cerebral microcirculation, such as capillary rarefication, may be present in these patients. We evaluated whether the presence of hypertension may affect the cerebral capillary architecture and function assessed by Intravoxel Incoherent Motion (IVIM) magnetic resonance imaging (MRI) in patients with continuous positive airway pressure (CPAP)-treated OSA.

Methods

Forty-one patients (88% male, mean age 57 ± 10 years) with moderate-to-severe OSA were selected and divided into two groups (normotensive vs. hypertensive). All hypertensive OSA patients were adherent with their antihypertensive medication. Cerebral microvascular structure was assessed in grey (GM) and white matter (WM) using an echo-planar diffusion imaging sequence with 14 different b values. A step-wise IVIM analysis algorithm was applied to compute true diffusion (D), perfusion fraction (f) and pseudo-diffusion (D*) values. Group comparisons were performed with the Wilcoxon-Mann-Whitney-Test. Regression analysis was adjusted for age.

Results

Diffusion- and perfusion-related indexes in middle-aged OSA normotensive patients were quantified in both tissue types (D [10−3 mm2/s]: GM = 0.83 ± 0.03; WM = 0.72 ± 0.03; f (%) GM = 0.09 ± 0.01; WM = 0.06 ± 0.01; D* [10−3 mm2/s]: GM = 7.72 ± 0.89; WM = 7.38 ± 0.98). In the examined tissue types, hypertension did not result in changes on the estimated MRI IVIM index values.

Conclusion

Based on IVIM analysis, cerebral microvascular structure and function showed no difference between hypertensive and normotensive patients with moderate-to-severe OSA treated with CPAP. Treatment adherence with antihypertensive drug regime and, in turn, controlled hypertension seems not to affect microvascular structure and perfusion of the brain.

Trial registration

ClinicalTrials.gov Identifier: NCT02493673

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Abbreviations

AHI:

apnoea-hypopnoea-index

BP:

blood pressure

CPAP:

continuous positive airway pressure

ESS:

Epworth Sleepiness Scale

HR:

heart rate

ODI:

oxygen desaturation index

OSA:

obstructive sleep apnoea

References

  1. Gaisl T, Bratton DJ, Kohler M (2015) The impact of obstructive sleep apnoea on the aorta. Eur Respir J 46(2):532–544

    Article  PubMed  Google Scholar 

  2. Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, Mooser V, Preisig M, Malhotra A, Waeber G, Vollenweider P, Tafti M, Haba-Rubio J (2015) Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med 3(4):310–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014

    Article  PubMed  PubMed Central  Google Scholar 

  4. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118(10):1080–1111

    Article  PubMed  Google Scholar 

  5. Loke YK, Brown JW, Kwok CS, Niruban A, Myint PK (2012) Association of obstructive sleep apnea with risk of serious cardiovascular events: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 5(5):720–728

    Article  PubMed  Google Scholar 

  6. Arzt M, Young T, Finn L, Skatrud JB, Bradley TD (2005) Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 172(11):1447–1451

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sanchez-de-la-Torre M, Campos-Rodriguez F, Barbe F (2013) Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med 1(1):61–72

    Article  PubMed  Google Scholar 

  8. Bulte DP, Chiarelli PA, Wise RG, Jezzard P (2007) Cerebral perfusion response to hyperoxia. J Cereb Blood Flow Metab 27(1):69–75

    Article  PubMed  Google Scholar 

  9. Jennum P, Borgesen SE (1989) Intracranial pressure and obstructive sleep apnea. Chest 95(2):279–283

    Article  CAS  PubMed  Google Scholar 

  10. Yadav SK, Kumar R, Macey PM, Richardson HL, Wang DJ, Woo MA, Harper RM (2013) Regional cerebral blood flow alterations in obstructive sleep apnea. Neurosci Lett 555:159–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Triantafyllou A, Anyfanti P, Pyrpasopoulou A, Triantafyllou G, Aslanidis S, Douma S (2015) Capillary rarefaction as an index for the microvascular assessment of hypertensive patients. Curr Hypertens Rep 17(5):33

    Article  PubMed  Google Scholar 

  12. Schwarz EI, Schlatzer C, Rossi VA, Stradling JR, Kohler M (2016) Effect of CPAP withdrawal on BP in OSA: data from three randomized controlled trials. Chest 150(6):1202–1210

    Article  PubMed  Google Scholar 

  13. Joyeux-Faure M, Baguet JP, Barone-Rochette G, Faure P, Sosner P, Mounier-Vehier C, Levy P, Tamisier R, Pepin JL (2018) Continuous positive airway pressure reduces night-time blood pressure and heart rate in patients with obstructive sleep apnea and resistant hypertension: the RHOOSAS randomized controlled trial. Front Neurol 9:318

    Article  PubMed  PubMed Central  Google Scholar 

  14. Prasad A, Dunnill GS, Mortimer PS, MacGregor GA (1995) Capillary rarefaction in the forearm skin in essential hypertension. J Hypertens 13(2):265–268

    Article  CAS  PubMed  Google Scholar 

  15. Jumar A, Harazny JM, Ott C, Kistner I, Friedrich S, Schmieder RE (2016) Improvement in retinal capillary rarefaction after valsartan treatment in hypertensive patients. JHC, The Journal of Clinicl Hypertension 18(11):1112–1118

    Article  CAS  Google Scholar 

  16. Nazzaro P, Schirosi G, Clemente R, Battista L, Serio G, Boniello E, Carratu PL, Lacedonia D, Federico F, Resta O (2008) Severe obstructive sleep apnoea exacerbates the microvascular impairment in very mild hypertensives. Eur J Clin Investig 38(10):766–773

    Article  CAS  Google Scholar 

  17. Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161(2):401–407

    Article  PubMed  Google Scholar 

  18. Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168(2):497–505

    Article  PubMed  Google Scholar 

  19. Le Bihan D, Turner R (1992) The capillary network: a link between IVIM and classical perfusion. Magn Reson Med 27(1):171–178

    Article  PubMed  Google Scholar 

  20. Lemke A, Laun FB, Klauss M, Re TJ, Simon D, Delorme S, Schad LR, Stieltjes B (2009) Differentiation of pancreas carcinoma from healthy pancreatic tissue using multiple b-values: comparison of apparent diffusion coefficient and intravoxel incoherent motion derived parameters. Investig Radiol 44(12):769–775

    Article  Google Scholar 

  21. Sigmund EE, Cho GY, Kim S, Finn M, Moccaldi M, Jensen JH, Sodickson DK, Goldberg JD, Formenti S, Moy L (2011) Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer. Magn Reson Med 65(5):1437–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sumi M, Nakamura T (2013) Head and neck tumors: assessment of perfusion-related parameters and diffusion coefficients based on the intravoxel incoherent motion model. AJNR Am J Neuroradiol 34(2):410–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Togao O, Hiwatashi A, Yamashita K, Kikuchi K, Momosaka D, Yoshimoto K, Kuga D, Mizoguchi M, Suzuki SO, Iwaki T, Van Cauteren M, Iihara K, Honda H (2018) Measurement of the perfusion fraction in brain tumors with intravoxel incoherent motion MR imaging: validation with histopathological vascular density in meningiomas. Br J Radiol 91(1085):20170912

    Article  PubMed  PubMed Central  Google Scholar 

  24. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 39(33):3021–3104

    Article  PubMed  Google Scholar 

  25. Thiel S, Lettau F, Rejmer P, Rossi C, Haile SR, Schwarz EI, Stoberl AS, Sievi NA, Boss A, Becker AS, Winklhofer S, Stradling JR, Kohler M (2018) Effects of short-term CPAP withdrawal on cerebral vascular reactivity measured by BOLD MRI in OSA: a randomised controlled trial. Eur Respir J

  26. Patel J, Sigmund EE, Rusinek H, Oei M, Babb JS, Taouli B (2010) Diagnosis of cirrhosis with intravoxel incoherent motion diffusion MRI and dynamic contrast-enhanced MRI alone and in combination: preliminary experience. J Magn Reson Imaging 31(3):589–600

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chen II, Prewitt RL, Dowell RF (1981) Microvascular rarefaction in spontaneously hypertensive rat cremaster muscle. Am J Phys 241(3):H306–H310

    CAS  Google Scholar 

  28. Sokolova IA, Manukhina EB, Blinkov SM, Koshelev VB, Pinelis VG, Rodionov IM (1985) Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension. Microvasc Res 30(1):1–9

    Article  CAS  PubMed  Google Scholar 

  29. Hasan KM, Manyonda IT, Ng FS, Singer DR, Antonios TF (2002) Skin capillary density changes in normal pregnancy and pre-eclampsia. J Hypertens 20(12):2439–2443

    Article  CAS  PubMed  Google Scholar 

  30. Brassard P, Tymko MM, Ainslie PN (2017) Sympathetic control of the brain circulation: appreciating the complexities to better understand the controversy. Auton Neurosci 207:37–47

    Article  PubMed  Google Scholar 

  31. Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5(5):347–360

    Article  CAS  PubMed  Google Scholar 

  32. Debbabi H, Bonnin P, Levy BI (2010) Effects of blood pressure control with perindopril/indapamide on the microcirculation in hypertensive patients. Am J Hypertens 23(10):1136–1143

    Article  CAS  PubMed  Google Scholar 

  33. Cho GY, Kim S, Jensen JH, Storey P, Sodickson DK, Sigmund EE (2012) A versatile flow phantom for intravoxel incoherent motion MRI. Magn Reson Med 67(6):1710–1720

    Article  PubMed  Google Scholar 

  34. Zhang CE, Wong SM, Uiterwijk R, Staals J, Backes WH, Hoff EI, Schreuder T, Jeukens CR, Jansen JF, van Oostenbrugge RJ (2017) Intravoxel incoherent motion imaging in small vessel disease: microstructural integrity and microvascular perfusion related to cognition. Stroke 48(3):658–663

    Article  PubMed  Google Scholar 

  35. Wu WC, Chen YF, Tseng HM, Yang SC, My PC (2015) Caveat of measuring perfusion indexes using intravoxel incoherent motion magnetic resonance imaging in the human brain. Eur Radiol 25(8):2485–2492

    Article  PubMed  PubMed Central  Google Scholar 

  36. Stieb S, Boss A, Wurnig MC, Ozbay PS, Weiss T, Guckenberger M, Riesterer O, Rossi C (2016) Non-parametric intravoxel incoherent motion analysis in patients with intracranial lesions: test-retest reliability and correlation with arterial spin labeling. Neuroimage Clin 11:780–788

    Article  PubMed  PubMed Central  Google Scholar 

  37. Pfefferbaum A, Sullivan EV (2003) Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming. Magn Reson Med 49(5):953–961

    Article  PubMed  Google Scholar 

  38. Pfefferbaum A, Adalsteinsson E, Rohlfing T, Sullivan EV (2010) Diffusion tensor imaging of deep gray matter brain structures: effects of age and iron concentration. Neurobiol Aging 31(3):482–493

    Article  PubMed  Google Scholar 

  39. Wong SM, Zhang CE, van Bussel FC, Staals J, Jeukens CR, Hofman PA, van Oostenbrugge RJ, Backes WH, Jansen JF (2017) Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging. NeuroImage Clinical 14:216–221

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chen JJ, Rosas HD, Salat DH (2011) Age-associated reductions in cerebral blood flow are independent from regional atrophy. NeuroImage 55(2):468–478

    Article  PubMed  Google Scholar 

  41. Brown WR, Thore CR (2011) Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol 37(1):56–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Galiano A, Mengual E, Garcia de Eulate R, Galdeano I, Vidorreta M, Recio M, Riverol M, Zubieta JL, Fernandez-Seara MA (2019) Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging. Brain imaging and behavior

  43. Asllani I, Habeck C, Borogovac A, Brown TR, Brickman AM, Stern Y (2009) Separating function from structure in perfusion imaging of the aging brain. Hum Brain Mapp 30(9):2927–2935

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lemaitre H, Goldman AL, Sambataro F, Verchinski BA, Meyer-Lindenberg A, Weinberger DR, Mattay VS (2012) Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging 33(3):617.e611–617.e619

    Article  Google Scholar 

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Funding

This work received support from the Swiss National Science Foundation (Grant no. 32003B_143365/1), Lunge Zurich and the University of Zurich Clinical Research Priority Program Sleep and Health. This work was also supported by the Clinical Research Priority Program of the University of Zurich for the Hypertension Research Network (HYRENE).

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Author notes

  1. ST and TG contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonology and Sleep Disorders Centre, University Hospital Zurich, Raemistrasse 100, Zurich, Switzerland

    Sira Thiel, Thomas Gaisl, Franziska Lettau & Malcolm Kohler

  2. Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland

    Andreas Boss & Cristina Rossi

  3. Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland

    Sebastian Winklhofer

  4. Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    Malcolm Kohler

Authors
  1. Sira Thiel
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  2. Thomas Gaisl
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  4. Andreas Boss
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  6. Malcolm Kohler
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  7. Cristina Rossi
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Contributions

Conception and design: MK, CR, AB. Funding: MK. Trial conduct: ST, FL. Analysis and interpretation of data: ST, FL, TG, CR, MK, AB, SW. Drafting the article: ST. Revising the article for important intellectual content and final approval: all authors.

Corresponding author

Correspondence to Sira Thiel.

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Conflict of interest

The authors declare the following conflicts of interest: ST, FL, CR, SW and AB have nothing to disclose. MK reports grants from University of Zurich and grants from Lunge Zurich during the conduct of the study. MK and TG report personal fees from Bayer AG, outside the submitted work.

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All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Thiel, S., Gaisl, T., Lettau, F. et al. Impact of hypertension on cerebral microvascular structure in CPAP-treated obstructive sleep apnoea patients: a diffusion magnetic resonance imaging study. Neuroradiology 61, 1437–1445 (2019). https://doi.org/10.1007/s00234-019-02292-z

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  • DOI: https://doi.org/10.1007/s00234-019-02292-z

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