EVALUATION OF THE RELATIONSHIP EVALUATION OF THE RELATIONSHIP BETWEEN H-FABP LEVELS AND THE BETWEEN H-FABP LEVELS AND THE

RISK OF CARDIAC DAMAGE IN RISK OF CARDIAC DAMAGE IN PATIENTS WITH OSASPATIENTS WITH OSAS

Burcu Oktay MDBurcu Oktay MD, Sadık Ardıç MD, Hikmet Firat MD, , Sadık Ardıç MD, Hikmet Firat MD, Erdem Akbal MD, Ramazan Akdemir MDErdem Akbal MD, Ramazan Akdemir MD

Diskapi Yildirim Beyazit Training and Research Hospital Diskapi Yildirim Beyazit Training and Research Hospital Ministry of Health/AnkaraMinistry of Health/Ankara

Obstructive Sleep Apnea SyndromeObstructive Sleep Apnea Syndrome

Male % 4 Male % 4 medical condition!!medical condition!! Female %2 Female %2

* Young T, Palta M, Dempsey J et al. The occurrence of sleep-disordered breathing among middle-aged adults. * Young T, Palta M, Dempsey J et al. The occurrence of sleep-disordered breathing among middle-aged adults. N. Engl. J. MedN. Engl. J. Med. 1993; 328(17): 1230–1235.. 1993; 328(17): 1230–1235.

OSASOSAS(1)(1)

- OSAS is an independent risk factor for Ischemic Heart - OSAS is an independent risk factor for Ischemic Heart Disease.Disease.

- CAD was evident in 50% of patients with clinically - CAD was evident in 50% of patients with clinically important OSAS. important OSAS.

Severity of OSAS Nocturnal STSeverity of OSAS Nocturnal ST Oxyhemoglobin desaturation segment changesOxyhemoglobin desaturation segment changes

1,Mayo Clin Proc. August 2004;79(8):1036-10461,Mayo Clin Proc. August 2004;79(8):1036-10462.Andreas S, Schultz R, Werner GS, Kreuzer H. Prevalence of obstructive sleep apnea in patient with coronary artery disease. Coron Artery Dis. 1996;7:541-5452.Andreas S, Schultz R, Werner GS, Kreuzer H. Prevalence of obstructive sleep apnea in patient with coronary artery disease. Coron Artery Dis. 1996;7:541-5453.Hanly P, Sasson Z, Zuberi N, Lunn K. ST segment depression during sleep in obstructive sleep apnea. Am J Cardiol.1993;71:1341-13453.Hanly P, Sasson Z, Zuberi N, Lunn K. ST segment depression during sleep in obstructive sleep apnea. Am J Cardiol.1993;71:1341-1345

OSASOSAS(4)(4)

RRecurrent hecurrent hyypopoxemiaxemia

STST--T segment T segment changes andchanges and nocturnal an nocturnal angginaina

SEROLOGIC MARKER???SEROLOGIC MARKER???

Heart Type Fatty Acid Binding Protein Heart Type Fatty Acid Binding Protein (h-fabp)(h-fabp)(1)(1)

15 kDA15 kDA weightweight.. SSmall mall ccytoplaytoplassmic protein.mic protein. It is releaseIt is releasedd from myoc from myocyteytes into circulation in large amounts s into circulation in large amounts

in the in the eventevent of acut of acutee myocardial ischemia. myocardial ischemia. This marker is extremely specific and senThis marker is extremely specific and senssitiitiveve to myocardial to myocardial

ischemia.ischemia.

Tomoaki Nakata at all. Human Heart type fatty acid binding protein as an eary diagnostic and prognostic marker in Acute Tomoaki Nakata at all. Human Heart type fatty acid binding protein as an eary diagnostic and prognostic marker in Acute coranary syndromeCardiology 2003:99:96-104coranary syndromeCardiology 2003:99:96-104

Heart Type Fatty Acid Binding Protein Heart Type Fatty Acid Binding Protein (2)(2)

. . Today itToday it’’s superiority is shown over the other s superiority is shown over the other cardiac markers in the early phase of acutcardiac markers in the early phase of acutee myocardial infarctionmyocardial infarction..

1.5 h 6 h 12-24 h1.5 h 6 h 12-24 h

H.A. Alhadı and K:A:A FOX. Do we need additional markers of myocyte necrosisi: the potential value of H.A. Alhadı and K:A:A FOX. Do we need additional markers of myocyte necrosisi: the potential value of heart fatty acid binding protein . QJ Med 2004; 97:187-198heart fatty acid binding protein . QJ Med 2004; 97:187-198

AIMAIM

In view of these findings, this study aims at In view of these findings, this study aims at detecting the cardiac damage occurring due to detecting the cardiac damage occurring due to nocturnal ischemia by using h-fabp in patients nocturnal ischemia by using h-fabp in patients with OSAS.with OSAS.

MATERIAL-METHODMATERIAL-METHOD(1)(1)

Prediagnosis of OSASPrediagnosis of OSAS Absence of previous CAD diagnosisAbsence of previous CAD diagnosis 21:00 21:00 CPK,CKMB,AST,troponinI,h-fabpCPK,CKMB,AST,troponinI,h-fabp

PolysomnographyPolysomnography

09:00 09:00 CPK,CKMB,AST,troponinI,h-fabpCPK,CKMB,AST,troponinI,h-fabp

MATERIAL-METHODMATERIAL-METHOD(2)(2)

AHIAHI≥≥55 ElectrocardiographyElectrocardiography EchocardiographyEchocardiography Myocardium perfusion syntigraphyMyocardium perfusion syntigraphy

Rule out CAD Rule out CAD

50 cases50 cases

Patient Group Patient Group

MATERIAL-METHODMATERIAL-METHOD(3)(3)

Control group;Control group; -No symptom of OSAS-No symptom of OSAS -Any history and risk factor of CAD-Any history and risk factor of CAD -PSG -PSG -EKG, EKO-EKG, EKO -19 cases-19 cases

MATERIAL-METHODMATERIAL-METHOD(4)(4)

SPSS software (Version 11.5) was used for SPSS software (Version 11.5) was used for data analysis.data analysis.

RESULTSRESULTS(1)(1)

Overall 69 cases (22f/47m) were included in the study.Overall 69 cases (22f/47m) were included in the study. Control group ; 19 cases / Patient group ; 50 casesControl group ; 19 cases / Patient group ; 50 cases Mean age was 48.02Mean age was 48.02±±9.59.5 None of patients had diabetes mellitus, congestive None of patients had diabetes mellitus, congestive

cardiac failure, cardiomyopathia, coronary artery cardiac failure, cardiomyopathia, coronary artery disease, renal failure, hypertension, and other systemic disease, renal failure, hypertension, and other systemic diseases.diseases.

RESULTSRESULTS(2)(2)

Patient and control groups;Patient and control groups;

AgeAge SexSex Smoking status p>0.05Smoking status p>0.05 BMIBMI

RESULTSRESULTS(3)(3)

Before SleepBefore Sleep After sleepAfter sleep CPK CPKCPK CPK CK-MB CK-MBCK-MB CK-MB AST ASTAST AST Troponin-I Troponin-ITroponin-I Troponin-I h-fabp h-fabph-fabp h-fabp

p > 0.05p > 0.05 In patient and control group In patient and control group

RESULTSRESULTS(4)(4)

Before sleepBefore sleep h-fabph-fabp After sleep h-fabpAfter sleep h-fabp

Patient groupPatient group 6.8 6.8 ±± 5.3 5.3 9.2 9.2 ±± 12.2 12.2 p>0.05p>0.05

Control groupControl group 3.463.46±±1.91.9 4.44.4±±3.9 3.9 p>0.05p>0.05

p=0.006p=0.006 p=0.022p=0.022

- All the other cardiac markers (CPK, CKMB, Troponin I, AST) remain insignificant between patient and control groups.

RESULTSRESULTS(5)(5)

When arithmetical mean of the h-fabp levels When arithmetical mean of the h-fabp levels before and after sleep was taken in the patient before and after sleep was taken in the patient group , it was found that;group , it was found that;

Mean value of the h-fabp is correlated with the Mean value of the h-fabp is correlated with the desaturated period ( desaturated period ( SaOSaO22< %80< %80 ) during sleep ) during sleep (p=0.04) .(p=0.04) .

RESULTSRESULTS(6)(6)

No significant relation was found between No significant relation was found between mean value of h-fabp and AHI, the number of mean value of h-fabp and AHI, the number of apneas, hypopneas and oxygen desaturation apneas, hypopneas and oxygen desaturation (p>0.05) .(p>0.05) .

RESULTSRESULTS(7)(7)

When patients were divided into three groups When patients were divided into three groups according to their AHI, no significant according to their AHI, no significant difference was found between groups in terms difference was found between groups in terms of h-fabp levels (p>0.05) .of h-fabp levels (p>0.05) .

DISCUSSIONDISCUSSION(1)(1)

There is still There is still no markerno marker that will predict that will predict cardiovascular morbidity and mortality or cardiovascular morbidity and mortality or reveal increased cardiac disease risk in patients reveal increased cardiac disease risk in patients with OSAS.with OSAS.

DISCUSSIONDISCUSSION(2)(2)

OSAS Hypoxia OSAS Hypoxia Myocardial ischemiaMyocardial ischemia

SaOSaO22<80%<80% H-FABPH-FABP

DISCUSSIONDISCUSSION(3)(3)

In patient group h-fabp levels were high, but In patient group h-fabp levels were high, but none of the patients had cardiac diseases that none of the patients had cardiac diseases that are detectable by electrocardiography, are detectable by electrocardiography, echocardiography and even myocardium echocardiography and even myocardium perfusion syntigraphy.perfusion syntigraphy.

DISCUSSIONDISCUSSION(4)(4)

This condition suggests that myocardial This condition suggests that myocardial ischemia occurring due to hypoxia caused by ischemia occurring due to hypoxia caused by apnea/hypopnea leads to increase in the h-apnea/hypopnea leads to increase in the h-fabp levels.fabp levels.

DISCUSSIONDISCUSSION(5)(5)

High h-fabp levelsHigh h-fabp levels might show us the patients might show us the patients who are in the who are in the asymptomic stageasymptomic stage , before , before disease appears. disease appears.

DISCUSSIONDISCUSSION(6)(6)

Absence of a difference in the patient group Absence of a difference in the patient group between h-fabp levels before and after sleep between h-fabp levels before and after sleep suggests that;suggests that;

Ishemic process induced by hypoxia continues Ishemic process induced by hypoxia continues throughout the day.throughout the day.

CONCLUSIONCONCLUSION

H-fabp seems to be a marker which allows the H-fabp seems to be a marker which allows the detection of the cardiac damage in the early detection of the cardiac damage in the early stage in OSAS patients.stage in OSAS patients.

Further studies that investigate the long term Further studies that investigate the long term development of cardiac dysfunction in relation development of cardiac dysfunction in relation with increasing levels of h-fabp in with increasing levels of h-fabp in asymptomatic patients are required.asymptomatic patients are required.

Thank you……..Thank you……..

Thank you…………..Thank you…………..

THANK YOU…..

ControlControl PatientPatient

Before sleep CPKBefore sleep CPK 92(30-281)92(30-281) 104(14-297)104(14-297)After sleep CPKAfter sleep CPK 90(36-290)90(36-290) 107(15-371)107(15-371)Before sleep CK-MBBefore sleep CK-MB 14.5 14.5 ±± 44 17.3 17.3 ±± 77After sleep CK-MBAfter sleep CK-MB 14.4 14.4 ±± 3.93.9 17.6 17.6 ±± 7.27.2Before sleep ASTBefore sleep AST 21 21 ±± 7.9 7.9 26 26 ±± 12.2 12.2After sleep ASTAfter sleep AST 18.3 18.3 ±± 5.3 5.3 26.2 26.2 ±± 13.4 13.4Before sleep TROPONIN-IBefore sleep TROPONIN-I 0.10.1 0.10.1After sleep TROPONIN-IAfter sleep TROPONIN-I 0.10.1 0.10.1Before sleep H-FABP*Before sleep H-FABP* 3.46 3.46 ±± 1.9 1.9 6.8 6.8 ±± 5.3 5.3After sleep H-FABP**After sleep H-FABP** 4.4 4.4 ±± 3.9 3.9 9.2 9.2 ±± 12.2 12.2

*p = 0.006**p = 0.022