Endothelial dysfunction and specific inflammation in obesity hypoventilation syndrome.
BACKGROUND
Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown.


OBJECTIVE
To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients.


METHODS
14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays.


RESULTS
OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11).


CONCLUSIONS
Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk.


BACKGROUND
ClinicalTrials.gov NCT00603096.
Borel
Jean-Christian
JC
INSERM ERI17, Laboratoire HP2, Université Joseph Fourier, Faculté de Médecine, Grenoble, France.
Roux-Lombard
Pascale
P
Tamisier
Renaud
R
Arnaud
Claire
C
Monneret
Denis
D
Arnol
Nathalie
N
Baguet
Jean-Philippe
JP
Levy
Patrick
P
Pepin
Jean-Louis
JL
D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010845:Obesity Hypoventilation Syndrome / Q000503:physiopathology*; D017286:Polysomnography
Am J Cardiol. 2008 Jan 1;101(1):98-101
18157973
J Clin Invest. 2007 Jan;117(1):175-84
17200717
J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S64-73
18987272
Eur Respir J. 2008 Jan;31(1):204-12
18166598
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1654-9
18566296
Am J Cardiol. 2007 Feb 19;99(4A):6B-14B
17307054
J Allergy Clin Immunol. 2005 May;115(5):911-9; quiz 920
15867843
Circulation. 2008 May 13;117(19):2467-74
18458169
Eur Respir J Suppl. 1993 Mar;16:5-40
8499054
Circulation. 2008 Sep 2;118(10):1080-111
18725495
Psychiatry Clin Neurosci. 2001 Jun;55(3):305-10
11422885
Australas Ann Med. 1967 Feb;16(1):20-32
6032026
Circ Res. 2008 Feb 1;102(2):218-25
17991878
Diabetes. 2007 Apr;56(4):901-11
17395738
Nature. 2006 Dec 14;444(7121):860-7
17167474
Eur Respir J. 2007 Aug;30(2):223-31
17459895
Chest. 2009 Sep;136(3):787-796
19567489
Br J Pharmacol. 2008 Jul;154(5):1047-54
18469848
Am J Med. 2005 Sep;118(9):948-56
16164877
Int J Cardiol. 2009 Feb 6;132(1):102-8
18190991
J Appl Physiol (1985). 2006 Aug;101(2):545-8
16614356
Chest. 2005 Mar;127(3):722-30
15764750
J Clin Invest. 2008 Sep;118(9):2992-3002
18769626
Eur J Endocrinol. 2008 May;158(5):R1-5
18426815
Chest. 2005 Aug;128(2):587-94
16100142
Circ Res. 2005 Apr 1;96(6):612-6
15802619
J Appl Physiol (1985). 2007 Apr;102(4):1687-95
17185492
J Am Coll Cardiol. 1994 Nov 15;24(6):1468-74
7930277
Chest. 2007 Jan;131(1):148-55
17218569
Chest. 2007 Oct;132(4):1322-36
17934118
J Allergy Clin Immunol. 2007 Mar;119(3):597-603
17261329
Thorax. 2009 Jul;64(7):631-6
19561283
Am Heart J. 2008 Jan;155(1):56-61
18082490
Eur Respir J. 1997 Dec;10(12):2847-52
9493672
Best Pract Res Clin Endocrinol Metab. 2005 Dec;19(4):547-66
16311216
Circulation. 2007 Mar 13;115(10):1285-95
17353456
J Am Coll Cardiol. 2007 Feb 6;49(5):531-8
17276175
Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):373-9
17138939
J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41
15582310
Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 1):1572-8
12406849
Hypertension. 2003 Sep;42(3):231-4
12860835
Diabetes. 2006 Aug;55(8):2340-6
16873699
Circulation. 2007 Oct 23;116(17):1931-41
17909104
Am J Med. 2004 Jan 1;116(1):1-7
14706658
Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):85-9
12524229
Thorax. 2002 Jan;57(1):75-6
11809994
Sleep. 1999 Aug 1;22(5):667-89
10450601
Diabetes. 2009 Mar;58(3):718-25
19074987
Chest. 2001 Aug;120(2):377-83
11502632
Eur Respir J. 2009 Jun;33(6):1467-84
19483049
Circulation. 2007 Oct 16;116(16):1812-20
17893273
J Am Coll Cardiol. 2003 May 21;41(10):1769-75
12767663