title: Endothelial dysfunction and hypertension in obstructive sleep apnea - Is it due to intermittent hypoxia?
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is not known whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity, hypoxia and circulating angiogenesis inhibitors in OSA.
  
  
  RESULTS
  We studies 95 subjects with and without OSA and hypertension. Endothelial-dependent vasodilation was assessed using brachial artery flow-mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The apnea-hypopnea indexes were 41 ± 5 and 48 ± 4 events/hr in normotensive OSA (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The sleep time spent with SaO2 < 90% (T < 90%) were 34 ± 8 and 40 ± 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% ± 0.5) compared to N-OSA (13.5% ± 0.5, P < 0.0001), H-non-OSA (10.5% ± 0.8, P < 0.01), and N-non-OSA (16.1% ± 1.0, P < 0.0001). There was no correlation between T < 90% and FMD. Both OSA groups had elevated levels of sFlt-1 (62.4 ± 5.9 and 63.9 ± 4.7 pg/ml) compared to N-non-OSA (32.1 ± 6.5, P = 0.0008 and P = 0.0004, respectively) and H-non-OSA (41.2 ± 7.0, P < 0.05 and P = 0.03, respectively). In contrast, sEng was only elevated in H-OSA (4.20 ± 0.17 ng/ml) compared with N-OSA (3.64 ± 0.14, P = 0.01) and N-non-OSA (3.48 ± 0.20, P = 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group (r = -0.38, P < 0.05).
  
  
  CONCLUSIONS
  These data show that patients with OSA and hypertension have marked impairment of FMD, independent of hypoxia exposure, which is associated with increased sEng.
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, University of California, Irvine, CA 90822, USA.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Jafari
authors.forename: Vahid
authors.initials: V
authors.lastname: Mohsenin
keywords: Angiogenesis inhibitors; Endothelial dysfunction; Hypertension; Sleep apnea
references.citation: N Engl J Med. 2004 Feb 12;350(7):672-83
references.pmid: 14764923
references.citation: Sleep Breath. 2010 Jun;14(2):131-6
references.pmid: 19777281
references.citation: Hypertension. 2009 Jan;53(1):64-9
references.pmid: 19015401
references.citation: J Am Coll Cardiol. 2004 Oct 19;44(8):1636-40
references.pmid: 15489096
references.citation: Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1185-92
references.pmid: 19461051
references.citation: Clin Exp Hypertens. 2004 Oct-Nov;26(7-8):753-61
references.pmid: 15702631
references.citation: N Engl J Med. 2000 May 11;342(19):1378-84
references.pmid: 10805822
references.citation: Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):351-62
references.pmid: 19249441
references.citation: J Biol Chem. 2002 Nov 15;277(46):43799-808
references.pmid: 12228247
references.citation: Blood. 2002 Dec 1;100(12):4001-10
references.pmid: 12433697
references.citation: Methods Mol Med. 2006;122:393-9
references.pmid: 16511996
references.citation: Vasc Med. 2009 Nov;14(4):351-60
references.pmid: 19808720
references.citation: Circulation. 2008 Apr 29;117(17):2270-8
references.pmid: 18413499
references.citation: Am J Respir Crit Care Med. 2006 Apr 15;173(8):897-901
references.pmid: 16439717
references.citation: Inflamm Res. 2002 Sep;51(9):464-70
references.pmid: 12365720
references.citation: Am J Respir Crit Care Med. 2005 Sep 1;172(5):613-8
references.pmid: 15901608
references.citation: BMC Med. 2010 Dec 20;8:86
references.pmid: 21171985
references.citation: Respir Med. 2011 May;105(5):801-7
references.pmid: 21277182
references.citation: N Engl J Med. 1993 Apr 29;328(17):1230-5
references.pmid: 8464434
references.citation: JAMA. 2000 Apr 12;283(14):1829-36
references.pmid: 10770144
references.citation: J Am Soc Nephrol. 2009 Oct;20(10):2235-45
references.pmid: 19608702
references.citation: Clin Cardiol. 2011 Dec;34(12):729-33
references.pmid: 22120636
references.citation: Am J Pathol. 2011 Jun;178(6):2665-81
references.pmid: 21641389
references.citation: Am J Cardiol. 2009 Dec 1;104(11):1478-83
references.pmid: 19932778
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: Sleep Med. 2009 Aug;10(7):759-62
references.pmid: 19185538
references.citation: Placenta. 2009 Mar;30 Suppl A:S38-42
references.pmid: 19138798
references.citation: Am J Hypertens. 2003 Apr;16(4):274-80
references.pmid: 12670743
references.citation: N Engl J Med. 2005 Nov 10;353(19):2034-41
references.pmid: 16282178
references.citation: Atherosclerosis. 1999 Aug;145(2):381-8
references.pmid: 10488967
references.citation: J Reprod Immunol. 2009 Nov;82(2):106-11
references.pmid: 19853925
references.citation: Am J Respir Crit Care Med. 2004 Feb 1;169(3):348-53
references.pmid: 14551167
references.citation: Sleep Med. 2013 Feb;14(2):165-71
references.pmid: 23266106
references.citation: Am J Obstet Gynecol. 2007 Apr;196(4):396.e1-7; discussion 396.e7
references.pmid: 17403433
references.citation: Hypertension. 2007 Jul;50(1):228-33
references.pmid: 17502493
references.citation: Heart Vessels. 2012 Jul;27(4):344-51
references.pmid: 21667051
references.citation: Am J Hypertens. 2012 Aug;25(8):854-61
references.pmid: 22647785