The Endothelium Dysfunction in Patients of Obstructive Sleep Apnea Syndrome

NCT ID: NCT01699126

Last Updated: 2018-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2013-08-31

Brief Summary

study Hypothesis: We hypothesize that CPAP could effectively improve the endothelial dysfunction by anti-inflammatory effect in patients of OSA,and compare to the effect of statin.

Detailed Description

Obstructive sleep apnea is a prevalent disorder that affect 2-4% adults in general population. Cardiovascular and Neurocognitive complication were the most common and severe consequence noted in patients of OSA. Endothelial dysfunction is the early pathologic changes in the vascular wall that precede to the clinical cardiovascular events. Endothelial dysfunction with the deficit of vascular relaxation will induce the development of hypertension. Endothelial dysfunction predict the occurrence of ischemic heart disease and cardiovascular events as stroke. The development of endothelial dysfunction significantly remark the early sign of the development of cardiovascular diseases.

Inflammation trigger by oxygen radical in the vascular system were the major pathogenesis of the endothelial dysfunction. Intermittent hypoxia in the patients of OSA during repeated apnea at night will increase the oxygen radicals therefore trigger the cascade of inflammation process. The inflammatory process could be mediated by the activation of the transcription factors such as NF-KB, AP-1 or from the pathway of HIF-1 cascade. Inflammatory cytokine such as HsCRP inducted by the activation of NF-KB and AP-1 will induce the interaction of monocytes and lymphocytes to further injury to the endothelium of vascular wall. TGF-B secreted by lymphocyte will create the remodeling by fibroblast which result in the thickening of vascular wall. Another pathway by VEGF, endothelin 1, or other protein modulated by HIF-1 is also proposed directly injure to the endothelium that cause the following cardiovascular events.

CPAP treatment for OSA were shown to lowering the severity of blood pressure and cardiovascular events in some reports. Although the effect for blood pressure lowering is still controversial, Most reports actually showed marginal effect on reducing BP to 2 mmHg by CPAP. There is still part of OSA patients with hypertension not responding to CPAP treatment.Besides of the effect of CPAP treatment, the compliance of CPAP is still a major concerning in the treatment of OSA. 60% of patients were reported to continue used CPAP in the well-supported sleep center in USA. Even the CPAP is covered by reimbursement in USA, the low compliance of CPAP impede the treatment of cardiovascular complication of OSA. To improve the control of the cardiovascular consequence of OSA, a convenient and well-tolerated intervention is mandatory. Statin, a powerful lipid-lowering medication, is found to have a significant anti-inflammatory effect in several reports. Statin is even suggested in the population of normal cholesterol to prevent the development of cardiovascular event. Statins exert cholesterol-independent, anti-inflammatory and immunomodulatory effects. Pleiotropic effects are typically mediated by HMG-CoA reductase inhibition, are dose dependent and occur rapidly after initiation of statin treatment. In order to evaluate and explore a safe and convenient method in the control of the cardiovascular complication of OSA, we conduct this study.

Conditions

Sleep Apnea, Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CPAP, Hypertension

evaluate the effect on FMD, blood pressure and inflammation after CPAP on OSA

Group Type: EXPERIMENTAL

CPAP

Intervention Type: DEVICE

Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group

CPAP and statin, Hypertension

evaluate the effect on FMD, blood pressure and inflammation after CPAP plus statin on OSA patients

Group Type: ACTIVE_COMPARATOR

CPAP

Intervention Type: DEVICE

Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group

Statin

Intervention Type: DRUG

Statin is an lipid lowering medication with anti-inflammatory effect.

OSA, statin, Hypertension

evaluate the effect on FMD, blood pressure and inflammation after statin treatment on OSA

Group Type: ACTIVE_COMPARATOR

Statin

Intervention Type: DRUG

Statin is an lipid lowering medication with anti-inflammatory effect.

Placebo

We will also measure the FMD, blood pressure and inflammation on patients with only life style modification as in all other patients

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

CPAP

Continuous Positive Airway Pressure is the routine treatment of OSA, patients will be randomly assigned into CPAP treatment group

Intervention Type: DEVICE

Statin

Statin is an lipid lowering medication with anti-inflammatory effect.

Intervention Type: DRUG

Other Intervention Names

rosuvastatin

Eligibility Criteria

Inclusion Criteria

• 1.OSA with AHI>30 2.Male patients with hypertension 3.LDL over 130 mg/dL without any lipid-lowering drug therapy in recent 6 months 4.Signed inform consent and cooperative

Exclusion Criteria

• 1.Non-cooperative 2.Can't sign inform consent. 3.Had proven major cardiovascular complication such as AMI, CVA. 4.Major chronic disorders and inflammatory disorders: such as DM, ESRD, COPD or rheumatoid arthritis. 5.Under anti-inflammatory medication: such as aspirin, NSAID, steroids, theophylline etc. 6.Acute of chronic infection 1 weeks between blood drawing period will be discarded 7.Study medication will be discontinued among subjects who develop myopathy (CK ≥10 times ULN and muscle aches or weakness) or a persistent elevation in ALT (≥3 times ULN on 2 consecutive tests).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

WAN-CHING Ho, M.D.

Role: PRINCIPAL_INVESTIGATOR

Taiwan Society of Cardiology

Locations

Chang Gang Memorial Hospital

Taoyuan District, , Taiwan

Countries

Taiwan

References

Luthje L, Andreas S. Obstructive sleep apnea and coronary artery disease. Sleep Med Rev. 2008 Feb;12(1):19-31. doi: 10.1016/j.smrv.2007.08.002. Epub 2007 Nov 1.

Reference Type: RESULT

PMID: 17936040 (View on PubMed)

Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93. doi: 10.1016/S0140-6736(08)61622-0. Epub 2008 Dec 26.

Reference Type: RESULT

PMID: 19101028 (View on PubMed)

Atkeson A, Yeh SY, Malhotra A, Jelic S. Endothelial function in obstructive sleep apnea. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):351-62. doi: 10.1016/j.pcad.2008.08.002.

Reference Type: RESULT

PMID: 19249441 (View on PubMed)

Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008 Apr 29;117(17):2270-8. doi: 10.1161/CIRCULATIONAHA.107.741512. Epub 2008 Apr 14.

Reference Type: RESULT

PMID: 18413499 (View on PubMed)

Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med. 2008 Feb 15;177(4):369-75. doi: 10.1164/rccm.200608-1190PP. Epub 2007 Nov 1.

Reference Type: RESULT

PMID: 17975198 (View on PubMed)

Gilmartin GS, Tamisier R, Curley M, Weiss JW. Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H778-85. doi: 10.1152/ajpheart.00653.2007. Epub 2008 Jun 6.

Reference Type: RESULT

PMID: 18539753 (View on PubMed)

Iturriaga R, Rey S, Del Rio R. Cardiovascular and ventilatory acclimatization induced by chronic intermittent hypoxia: a role for the carotid body in the pathophysiology of sleep apnea. Biol Res. 2005;38(4):335-40. doi: 10.4067/s0716-97602005000400004.

Reference Type: RESULT

PMID: 16579514 (View on PubMed)

Williams B. The year in hypertension. J Am Coll Cardiol. 2008 May 6;51(18):1803-17. doi: 10.1016/j.jacc.2008.03.010. No abstract available.

Reference Type: RESULT

PMID: 18452788 (View on PubMed)

Campos-Rodriguez F. Screening for sleep apnea in patients with resistant hypertension. Am J Hypertens. 2008 Jul;21(7):728. doi: 10.1038/ajh.2008.193. No abstract available.

Reference Type: RESULT

PMID: 18584016 (View on PubMed)

Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007 Apr 23;167(8):757-64. doi: 10.1001/archinte.167.8.757.

Reference Type: RESULT

PMID: 17452537 (View on PubMed)

Phillips CL, Yee B, Yang Q, Villaneuva AT, Hedner J, Berend N, Grunstein R. Effects of continuous positive airway pressure treatment and withdrawal in patients with obstructive sleep apnea on arterial stiffness and central BP. Chest. 2008 Jul;134(1):94-100. doi: 10.1378/chest.07-3121. Epub 2008 Mar 17.

Reference Type: RESULT

PMID: 18347202 (View on PubMed)

Other Identifiers

98-2167B

Identifier Type: -

Identifier Source: org_study_id