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  • Print publication year: 2012
  • Online publication date: January 2013

Chapter 7 - Patent foramen ovale, obstructive sleep apnea, and its association with ischemic stroke

Summary

The sleep apnea syndrome occurs in 4% of adult men and 2% of adult women. Inflammation and hypoxia are intertwined at the molecular, cellular, and clinical levels. Sleep apnea influences heart rate variability, during sleep and during wakefulness. It is also an independent risk factor for stroke. Sleep apnea may also lead to cognitive dysfunction from the effects of chronic hypoxia and sympathetic stress associated with small-vessel disease in the brain, white matter ischemia, and lacunar strokes. This syndrome is a modifiable risk factor and therefore efforts to control this condition in patients at risk of vascular disease is a clinical endeavor that should be pursued vigorously, even though clinical research needs to persist in its quest to answer pressing pathophysiological questions. Emerging evidence suggests that restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) represent risk factors for cardio- and cerebrovascular disease, even leading to stroke.

References

1. ConheimJ. Handbuch fur Artze und Studierende. Berlin: Hirschwald, 1877.
2. MeissnerI, WhisnantJP, KhandheriaBK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke prevention: assessment of risk in a community. Mayo Clin Proc 1999; 74: 862–9.
3. HamannGF, Schätzer-KlotzD, FröhligG, et al. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale. Neurology 1998; 50: 1423–8.
4. SpencerMP, MoehringMA, JesurumJ, et al. Power m-mode transcranial Doppler for diagnosis of patent foramen ovale and assessing transcatheter closure. J Neuroimaging 2004; 14: 342–9.
5. SerenaJ, SeguraT, Perez-AyusoMJ, et al. The need to quantify right-to-left shunt in acute ischemic stroke: a case-control study. Stroke 1998; 29: 1322–8.
6. JaussM, ZanetteE. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc Dis 2000; 10: 490–6.
7. Di TullioM, SaccoRL, VenketasubramanianN, et al. Comparison of diagnostic techniques for the detection of a patent foramen ovale in stroke patients. Stroke 1993; 24: 1020–4.
8. AzarbalB, TobisJ. Interatrial communications, stroke, and migraine headache. Appl Neurol 2005; 1: 22–36.
9. HagenPT, ScholzDG, EdwardsWD, et al. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 1984; 59: 17–20.
10. FisherDC, FisherEA, BuddJH, et al. The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study. Chest 1995; 107: 1504–9.
11. PentherP. Patent foramen ovale: an anatomical study. Apropos of 500 consecutive autopsies. Arch Mal Coeur Vaiss 1994; 87: 15–21.
12. LynchJJ, SchuchardGH, GrossCM, et al. Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography. Am J Cardiol 1984; 53: 1478–80.
13. WebsterMW, ChancellorAM, SmithHJ, et al. Patent foramen ovale in young stroke patients. Lancet 1988; 2: 11–12.
14. LechatP, MasJL, LascaultG, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988; 318: 1148–52.
15. CabanesL. MasJL, CohenA, et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography. Stroke 1993; 24: 1865–73.
16. OverellJR, BoneI, LeesKR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000; 55: 1172–9.
17. KerutEK, NorfleetWT, PlotnickGD, et al. Patent foramen ovale: a review of associated conditions and the impact of physiological size. J Am Coll Cardiol 2001; 38: 613–23.
18. SaccoRL, EllenbergJH, MohrJP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989; 25: 382–90.
19. HandkeM, HarloffA, OlschewskiM, et al. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007; 357: 2262–8.
20. PettyGW, KhandheriaBK, MeissnerI, et al. Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events. Mayo Clin Proc 2006; 81: 602–8.
21. KentDM, TrikalinosTA, ThalerDE, et al. Patent foramen ovale and cryptogenic stroke. N Engl J Med 2008; 358: 1519–20.
22. HutchinsonEC, AchesonEJ. Strokes: natural history, pathology and surgical treatment. Vol. 4. In: JohnWalton, ed. Major Problems in Neurology. Philadelphia, PA: Saunders, 1975.
23. FalkV, WaltherT, KrankenbergH, et al. Trapped thrombus in a patent foramen ovale. Thorac Cardiovasc Surg 1997; 45: 90–2.
24. CramerSC, RordorfG, MakiJH, et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the paradoxical emboli from large veins in ischemic stroke (PELVIS) study. Stroke 2004; 35: 46–50.
25. BerthetK, LavergneT, CohenA, et al. Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke 2000; 31: 398–403.
26. PezziniA, Del ZottoE, MagoniM, et al. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke 2003; 34: 28–33.
27. KarttunenV, HiltunenL, RasiV, et al. Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale. Blood Coagul Fibrinolysis 2003; 14: 261–8.
28. LichyC, ReunerKH, BuggleF, et al. Prothrombin G20210A mutation, but not factor V Leiden, is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia. Cerebrovasc Dis 2003; 16: 83–7.
29. MoonRE, CamporesiEM, KissloJA. Patent foramen ovale and decompression sickness in divers. Lancet 1989; 1: 513–14.
30. TortiSR, BillingerM, SchwerzmannM, et al. Risk of decompression illness among 230 divers in relation to the presence and size of patent foramen ovale. Eur Heart J 2004; 25: 1014–20.
31. ErdemI, YildizS, UzunG, et al. Cerebral white-matter lesions in asymptomatic military divers. Aviat Space Environ Med 2009; 80: 2–4.
32. GemppE, SbardellaF, StephantE, et al. Brain MRI signal abnormalities and right-to-left shunting in asymptomatic military divers. Aviat Space Environ Med 2010; 81: 1008–12.
33. BillingerM, ZbindenR, MordasiniR, et al. Patent foramen ovale closure in recreational divers: effect on decompression illness and ischaemic brain lesions during long-term follow-up. Heart 2011; 97: 1932–7.
34. DienerHC, KurthT, DodickD. Patent foramen ovale, stroke, and cardiovascular disease in migraine. Curr Opin Neurol 2007; 20: 310–19.
35. ColomboB, Dalla LiberaD, ComiG. Brain white matter lesions in migraine: what’s the meaning?Neurol Sci 2011; 32: S37–40.
36. DowsonA, MullenMJ, PeatfieldR, et al. Migraine intervention with STARFlex technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation 2008; 117: 1397–404.
37. KlötzschC, SliwkaU, BerlitP, et al. An increased frequency of patent foramen ovale in patients with transient global amnesia: analysis of 53 consecutive patients. Arch Neurol 1996; 53: 504–8.
38. FortezaAM, KochS, Campo-BustilloI, et al. Transcranial Doppler detection of cerebral fat emboli and relation to paradoxical embolism: a pilot study. Circulation 2011; 123: 1947–52.
39. RigatelliG, RigatelliG, RossiP, et al. Normal angiogram in acute coronary syndromes: the underestimated role of alternative substrates of myocardial ischemia. Int J Cardiovasc Imaging 2004; 20: 471–5.
40. HuglB, Klein-WeigelP, PoschL, et al. Peripheral ischemia caused by paradoxical embolization: an underestimated problem?Mt Sinai J Med 2005; 72: 200–6.
41. CaranoN, AgnettiA, HaglerDJ, et al. Acute myocardial infarction in a child: possible pathogenic role of patent foramen ovale associated with heritable thrombophilia. Pediatrics 2004; 114: e255–8.
42. SteuberC, PanznerB, SteuberT, et al. Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve. Ophthalmologe 1997; 94: 871–6.
43. KonstantinidesS, GeibelA, KasperW, et al. Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism. Circulation 1998; 97: 1946–51.
44. ShnaiderH, ShiranA, LorberA. Right ventricular diastolic dysfunction and patent foramen ovale causing profound cyanosis. Heart 2004; 90: e31.
45. NagayoshiY, ToyamaK, KawanoH, et al. Platypnea-orthodeoxia syndrome combined with multiple congenital heart anomalies. Intern Med 2005; 44: 453–7.
46. GuérinP, LambertV, GodartF, et al. Transcatheter closure of patent foramen ovale in patients with platypnea-orthodeoxia: results of a multicentric French registry. Cardiovasc Intervent Radiol 2005; 28: 164–8.
47. SolimanA, ShanoudyH, LiuJ, et al. Increased prevalence of patent foramen ovale in patients with severe chronic obstructive pulmonary disease. J Am Soc Echocardiogr 1999; 12: 99–102.
48. AllemannY, HutterD, LippE, et al. Patent foramen ovale and high-altitude pulmonary edema. JAMA 2006; 296: 2954–8.
49. UenoY, ShimadaY, TanakaR, et al. Patent foramen ovale with atrial septal aneurysm may contribute to white matter lesions in stroke patients. Cerebrovasc Dis 2010; 30: 15–22.
50. LiuJR, PlötzBM, RohrA, et al. Association of right-to-left shunt with frontal white matter lesions in T2-weighted MR imaging of stroke patients. Neuroradiology 2009; 51: 299–304.
51. PhillipsonEA. Sleep apnea: a major public health problem. N Engl J Med 1993; 328: 1271–3.
52. ShamsuzzamanAS, GershBJ, SomersVK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 2003; 290: 1906–14.
53. NarkiewiczK, SomersVK. Sympathetic nerve activity in obstructive sleep apnea. Acta Physiol Scand 2003; 177: 385–90.
54. MorganBJ, ReichmuthKJ, PeppardPE, et al. Effects of sleep-disordered breathing on cerebrovascular regulation: a population-based study. Am J Respir Crit Care Med 2010; 182: 1445–52.
55. UrbanoF, RouxF, SchindlerJ, et al. Impaired cerebral autoregulation in obstructive sleep apnea. J Appl Physiol 2008; 105: 1852–7.
56. LavieL. Sleep-disordered breathing and cerebrovascular disease: a mechanistic approach. Neurol Clin 2005; 23: 1059–75.
57. PartinenM, PalomäkiH. Snoring and cerebral infarction. Lancet 1985; 2: 1325–6.
58. KoskenvuoM, KaprioJ, TelakiviT, et al. Snoring as a risk factor for ischaemic heart disease and stroke in men. Br Med J (Clin Res Ed) 1987; 294: 16–19.
59. JennumP, Schultz-LarsenK, DavidsenM, et al. Snoring and risk of stroke and ischemic heart disease in a 70 year old population. A 6-year follow up study. Int J Epidemiol 1994; 23: 1159–64.
60. HuFB, WillettWC, MansonJE, et al. Snoring and risk of cardiovascular disease in women. J Am Coll Cardiol 2000; 35: 308–13.
61. SmirneS, PalazziS, ZucconiM, et al. Habitual snoring as a risk factor for acute vascular disease. Eur Respir J 1993; 6: 1357–61.
62. NeauJP, MeuriceJC, PaquereauJ, et al. Habitual snoring as a risk factor for brain infarction. Acta Neurol Scand 1995; 92: 63–8.
63. ShaharE, WhitneyCW, RedlineS, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001; 163: 19–25.
64. BassettiC, AldrichMS. Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep 1999; 22: 217–23.
65. ParraO, ArboixA, BechichS, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med 2000; 161: 375–80.
66. YaggiHK, ConcatoJ, KernanWN, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353: 2034–41.
67. ShanoudyH, SolimanA, RaggiP, et al. Prevalence of patent foramen ovale and its contribution to hypoxemia in patients with obstructive sleep apnea. Chest 1998; 113: 91–6.
68. BeelkeM, AngeliS, Del SetteM, et al. Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a transcranial Doppler ultrasound study. Sleep Med 2003; 4: 219–23.
69. BeelkeM, AngeliS, Del SetteM, et al. Obstructive sleep apnea can be provocative for right-to-left shunting through a patent foramen ovale. Sleep 2002; 25: 856–62.
70. JohanssonMC, ErikssonP, PekerY, et al. The influence of patent foramen ovale on oxygen desaturation in obstructive sleep. Eur Respir J 2007; 29: 149–55.
71. SilverB, GreenbaumA, McCarthyS. Improvement in sleep apnea associated with closure of a patent foramen ovale. J Clin Sleep Med 2007; 3: 295–6.
72. PinetC, OrehekJ. CPAP suppression of awake right-to-left shunting through patent foramen ovale in a patient with obstructive sleep apnea. Thorax 2005; 60: 880–1.
73. AlchanatisM, ParadellisG, PiniH, et al. Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure. Respiration 2000; 67: 367–71.
74. LaksL, LehrhaftB, GrunsteinRR, et al. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J 1995; 8: 537–41.
75. SannerBM, DoberauerC, KonermannM, et al. Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med 1997; 157: 2483–7.
76. KriegerJ, SforzaE, ApprillM, et al. Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. Chest 1989; 96: 729–37.
77. OzdemirO, BeletskyV, HachinskiV, et al. Cerebrovascular events on awakening, patent foramen ovale and obstructive sleep apnea syndrome. J Neurol Sci 2008 ; 268: 193–4.
78. OzdemirAO, TamayoA, MunozC, et al. Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism. J Neurol Sci 2008; 275: 121–7.
79. CicconeA, NobiliL, RoccatagliataDV, et al. Causal role of sleep apneas and patent foramen ovale in wake-up stroke. Neurology 2011; 76: A170.
80. FurlanAJ, ReismanM, MassaroJ, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366: 991–9.