research article early left ventricular systolic and...

Research ArticleEarly Left Ventricular Systolic and Diastolic Dysfunction inPatients with Newly Diagnosed Obstructive Sleep Apnoea andNormal Left Ventricular Ejection Fraction

Lisulov Popovic Danica1 Mirjana Krotin1 Marija Zdravkovic1 Ivan Soldatovic2 DarkoZdravkovic1 Milica Brajkovic1 Vera Gardijan1 Jelena Saric1 Ruzica Pokrajac1 DraganLovic3 Predrag Stevanovic1 Milina Tancic Gajic4 and Miodrag Vukcevic1

1 University Clinical Hospital Center Bezanijska Kosa Faculty of Medicine University of Belgrade 11000 Belgrade Serbia2 Institute for Biomedical Statistics Faculty of Medicine University of Belgrade 11000 Belgrade Serbia3 Clinic for Internal Disease Intermedica 18000 Nis Serbia4 Institute for Endocrinology Metabolic Disease and Obesity Faculty of Medicine University of Belgrade 11000 Belgrade Serbia

Correspondence should be addressed to Marija Zdravkovic sekcijakardioloskagmailcom

Received 27 November 2013 Accepted 22 January 2014 Published 27 February 2014

Academic Editors S Di Filippo and Y Murakawa

Copyright copy 2014 Lisulov Popovic Danica et alThis is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The aim of the study was to evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolicand regional systolic dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction Methods 125 consecutivepatients were prospectively enrolled in the study Control group consisted of 78 asymptomatic age-matched healthy subjects whodid not have any cardiovascular and respiratory diseases All patients had undergone overnight polysomnography and standardtransthoracic and tissue Doppler imaging echocardiogram Results The EA ratio and the peak E wave at mitral flow weresignificantly lower and the peak A wave at mitral flow was significantly higher in OSA patients compared with control subjectsLeft ventricle isovolumetric relaxation time (IVRT) and mitral valve flow propagation (MVFP) were significantly longer in OSApatients than in controls Tissue Doppler derived 1198781015840 amplitude of lateral part at mitral valve (1198781015840Lm) and 1198641015840 wave amplitudes bothat the lateral (1198641015840Lm) and septal parts of the mitral valve (1198641015840Sm) were significantly lower in OSA patients compared to controlsConclusion Newly diagnosed OSA patients with normal global LV function have significantly impaired diastolic function andregional longitudinal systolic function OSA is independently associated with these changes in LV function

1 Introduction

Obstructive sleep apnoea (OSA) is a common conditionaffecting about 5ndash15 of adult population in developedcountries Prevalence is increasing with age obesity andchronic diseases [1 2] The main characteristics are repet-itive apnoea or hypopnoea induced by narrowing of theupper airways during sleep Hypoxia and hypercapnia dueto repetitive obstructive apnoea consequently affect the bal-ance in myocardial oxygen demand and supply The resultis consequent development of myocardial ischaemia andcompensatory activation of sympathetic nervous systemThecardiovascular involvement is an increase in left ventricular

(LV) afterload and a decrease in LV preload [2 3] Thereare lots of studies demonstrating correlation of OSA andincreased cardiovascular morbidity and mortality further-more OSA is regarded as an independent risk for overall andcardiovascular morbidity and mortality [4ndash6] On the otherhand patients with OSA frequently have a great number ofstandard well-known cardiovascular risk factors

Manifested heart failure is the worst consequence ofthe left ventricular dysfunction caused by OSA Howevermost of the patients with OSA without other cardiovasculardisease usually exhibit normal LV ejection fraction (EF)nevertheless they still may have clinical signs of LV systolicdysfunction This is due to the fact that normal value of

Hindawi Publishing Corporatione Scientific World JournalVolume 2014 Article ID 898746 7 pageshttpdxdoiorg1011552014898746

2 The Scientific World Journal

LVEF does not always mean normal LV systolic functionOn the other hand diastolic function is often impaired inOSA [7ndash9] Myocardial ischemia and oxidative stress are thepathophysiological explanations of these disturbances [1011] Left ventricular systolic function is generated by radialand longitudinal shortening and both processes are veryimportant Radial shortening is predominantly dependent onthe contraction of circumferential myocardial fibres in themidwall more resistant to ischemia However longitudinalshortening is generated by both longitudinal subendocardialand subepicardial fibres where subendocardium is morevulnerable tomyocardial ischaemia Hence assessment of LVlongitudinal function might be a sensitive marker for detect-ing subclinical alterations in LV systolic performance andthe early detection of the left ventricular systolic dysfunction[7 12]

Mitral annular velocity evaluated by tissue Dopplerimaging (TDI) is a sensitive marker of the LV longitudinaldysfunction We assumed that early left ventricular systolicand diastolic dysfunctions are present in patients with newlydiagnosed OSA even when left ventricle ejection fraction isnormal Thus the aim of the study was to evaluate whetherobstructive sleep apnea (OSA) contributes directly to leftventricular (LV) diastolic and regional systolic dysfunctionin newly diagnosed OSA with normal left ventricle ejectionfraction

2 Materials and Methods

21 Design and Settings A total of 792 consecutive patientswho had undergone overnight polysomnography (PSG) withnewly diagnosed OSA at the Center for Sleep MedicineBezanijska kosa from January 2011 to January 2013 wereenrolled in the study Among them the patients who met thefollowing conditions that might have had an influence on theresults of echocardiographic parameters were excluded (1)central sleep apnoea (2) history of coronary artery diseaseor electrocardiographic changes suggestive of myocardialinfarction (3) proved myocardial ischaemia at the ergometrytesting (4) global LV systolic dysfunction (LVEF lt 50) ora history of congestive heart failure (5) diabetes mellitus(6) moderate to severe valvular heart diseases (7) hyper-trophic cardiomyopathy (8) history of chronic obstructivepulmonary disease or asthma (9) atrial fibrillation (10)previous diagnosis of OSA andor the previous use of con-tinuous positive airway pressure therapy and (11) chronicrenal impairment (serum creatinine more than 112 120583molL)including chronic hemodialysis patients who did not haveOSA (ie lt5 eventsh of apnea hypopnea index (AHI))All patients had complained of daytime sleepiness andorloud snoring The investigation was done to the principlesenumerated in theHelsinki Declaration of 1975 and informedconsent was obtained after full explanation of the procedureFinally 125 patients (mean age 58plusmn11 years minimal 21 andmaximal 75) were enrolled in the study

In addition a total of age matched 78 asymptomatichealthy subjects who did not have any cardiovascular andrespiratory symptoms volunteer to participate in study were

enrolled in study as a control group All participants from thecontrol group had neither hypertension nor coronary arterydisease and all had normal ergometry testing and normalarterial tension during three repeated measurements

All patients had undergone overnight polysomnographyto determine the presence and severity of OSA Completetransthoracic echocardiogram had been also performed nextmorning The two investigated groups were age matchedconsidering aging bias in left ventricle diastolic dysfunctionThe study protocol was approved by the Ethics Committee ofUniversity of Belgrade and all subjects gave written informedconsent for the enrollment

22 Sleep Study Overnight fully attended PSG monitoringwas performed with the Alice 4 Sleep System (RespironicsInc Murrysville PA USA) in the referral Center for SleepMedicine using standard recording techniques and preciseprotocol of PSG monitoring [13] Surface electrodes wereapplied to perform electroencephalogram chin electromyo-gram electrocardiogram and electrooculography Airflowwasmonitored using an air pressure sensor placed at the noseand thermistor placed at the nose and mouth and arterialoxygen saturation (SaO

2) was recorded continuously with a

pulse oximeter Apnea was defined as the disappearance ofairflow for over 10 s hypopneawas defined as a 50or greaterdecrease in airflow lasting for more than 10 s associatedwith arousal or a 3 or greater decrease in arterial oxygensaturation from the baseline level The AHI was calculated asthe total number of apnea and hypopnea episodes per hourof sleep According to the AHI the patient was classifiedas having OSA when the obstructive component was over5 events per hour Severe OSA was classifies as AHI gt 30eventsh [14]

23 Standard Echocardiography Echocardiography was per-formed in the left lateral decubitus position with a commer-cially available ultrasound machine (Vivid VII GE Health-care Milwaukee WI USA) and 3S-RS (35MHz) probeAll images were obtained from standard parasternal andapical position using 2D M-mode and Doppler echocar-diographic techniques All examinations were performed byan experienced cardiologist who was blind for the resultsof polysomnography The LV end-diastolic and end-systolicdimensions as well as interventricular septum and posteriorwall thicknesses were obtained from M-mode echocardio-graphy [15] LVEF was measured using biplane Simpsonrsquosmethod according to the recommendation of EuropeanAsso-ciation for Echocardiography [16] Right ventricle dimension(RV) and right ventricular fractional area change (FAC RV)were also measured

Pulse Doppler sample volume was placed at the mitralvalve tips in the apical four-chamber view to record LV inflowvelocity From LV inflow velocity early diastolic peak flowvelocity (119864) late diastolic peak flow velocity (119860) 119864119860 ratioand deceleration time of the 119864 wave velocity were measuredand then calculated from three consecutive cardiac cycles[15] Isovolumic contraction and relaxation times were alsocalculated from LV inflow and outflow tract velocities [16]

The Scientific World Journal 3

Table 1 Clinical characteristics of OSA patients and control subjects

Patients (119899 = 125) Controls (119899 = 78) 119875

Males (119899 ) 91 (728) 36 (462) lt0001lowastlowast

Age (years) 516 plusmn 107 488 plusmn 102 0073BMI (kgm2) 316 plusmn 56 249 plusmn 28 lt0001lowastlowast

BMI 30+ (119899 ) 67 (536) 5 (64) lt0001lowastlowast

BSA (m2) 212 plusmn 023 191 plusmn 019 lt0001lowastlowast

Hypertension (119899 ) 69 (556) 5 (64) lt0001lowastlowast

Hypercholesterolemia (119899 ) 94 (752) 51 (654) 0132Cholesterol (mmolL) 602 plusmn 127 579 plusmn 113 0187Hypertriglyceridemia (119899 ) 56 (448) 11 (141) lt0001lowastlowast

Triglycerides (mmolL) 199 plusmn 120 128 plusmn 088 lt0001lowastlowast

Low HDL (119899 ) 35 (280) 11 (141) 0021lowast

HDL (mmolL) 125 plusmn 031 148 plusmn 032 lt0001lowastlowast

Smoking (119899 ) 45 (360) 16 (205) 0019lowast

Results are presented as 119899 () or mean plusmn SDBMI body mass index BSA body surface area HDL high density lipoproteinslowastlowastMeans high significant lowastmeans significant

24 Tissue Doppler Echocardiography Tissue Doppler echo-cardiography was recorded from the apical four-chamberview with the pulse-wave Doppler sample volume placed onthe septal and lateral corners of the mitral annulus Care wastaken to ensure an ultrasound beam parallel to the directionof themitral annularmotion Filters were set to exclude high-frequency signals and gains were set to obtain clear tissuesignals with minimal background noise Peak systolic (1198781015840)peak early (1198641015840) and late (1198601015840) diastolic mitral septum andlateral annular velocities were measured [14 15]

25 Statistical Analysis Data were expressed as mean valuesplusmn SD Frequencies were expressed as percentages Studentrsquosunpaired 119905-test was used to compare the means of the contin-uous variables between the group of patients with OSA andcontrol group Categorical variables were compared using 1199092test Multivariate linear regression analysis was used to deter-mine whether severe OSA was an independent parameter forearly impaired LV diastolic and systolic function after adjust-ment for parameters which were significantly correlated withLV tissue Doppler parameters in univariate analyses Sincehypertension and elevated BMI are intrinsically connectedto OSA avoiding OSA patients with these characteristicswould not give the proper sample characteristics representingthe whole OSA group so adjustments of tissue Dopplerechocardiographic parameters to BMI and hypertension havebeen done in order to overcome this confounding bias

Computer calculations were performed using the SPSScomputer program (Version 110 SPSS Chicago IL USA) A119875 value of lt005 was considered statistically significant

3 Results

31 Patient Characteristics Clinical characteristics of OSApatients and control subjects are shown in Table 1 Bothgroups were similar regarding to incidence of hypercholes-terolemia and cholesterol level However OSA patients

Table 2 The results of polysomnography

Polysomnography Mean plusmn SD Median(minimumndashmaximum)

AHI index (119899h) 372 plusmn 217 34 (6ndash1081)Mean SaO2 () 921 plusmn 43 93 (75ndash97)ODI index (eventsh) 324 plusmn 265 227 (08ndash1040)The lowest SaO2 ()gt2 sec () 731 plusmn 161 79 (0ndash93)

Epworth score 121 plusmn 61 13 (1ndash26)Results are presented as mean plusmn SD and median (minimumndashmaximum)AHI apnea hypopnea index SaO2 oxygen saturation ODI index oxygendesaturation index

had significantly higher BMI and consequently significantlyhigher prevalence of hypertriglyceridemia compared withcontrol subjects The proportion of smokers in group of OSAwas also significantly higher Patients with OSA had signif-icantly higher incidence of hypertension and significantlyhigher both systolic and diastolic arterial pressure

The results of polysomnography are described in Table 2According to AHI even 81 patients (65) had severe newlydiagnosed OSA

32 Echocardiography Standard 2D echocardiographicmeasurements left ventricular end-diastolic dimension(LVEDD) and left ventricular end-systolic dimension(LVESD) were significantly larger in patients with OSAcompared to control subjects as well as interventricularseptum thickness (IVS) and posterior wall thickness(PW) There were significant differences in right ventricledimension (RV) and right ventricular fractional area change(FAC RV) However parameters of global left ventricularsystolic function global ejection fraction (EF) and fractionof shortening (FS) were similar in both groups (Table 3)


Table 3 Echocardiographic parameters of OSA patients and control subjects


LVEDD (cm) 509 plusmn 049 478 plusmn 042 lt0001lowastlowast

LVESD (cm) 321 plusmn 041 306 plusmn 041 lt0001lowastlowast

IVSd (cm) 111 plusmn 014 097 plusmn 013 lt0001lowastlowast

PWd (cm) 098 plusmn 013 085 plusmn 011 lt0001lowastlowast

EF () 658 plusmn 67 659 plusmn 73 0912FS () 365 plusmn 54 365 plusmn 58 0960RV (cm) 237 plusmn 037 224 plusmn 032 0011lowast

FAC RV () 4203 plusmn 920 4608 plusmn 1156 0010lowast

Results are presented as mean plusmn SDLVEDD left ventricular end-diastolic diameter LVESD left ventricular end-systolic diameter IVSd interventricular thickness (diastole) PWd left ventricularposterior wall diameter (diastole) EF ejection fraction FS fraction of shortening RV right ventricular diameter FAC RV right ventricular fractional areachangelowastlowastMeans high significant lowastmeans significant

Table 4 Transmitral and tissue Doppler imaging parameters of OSA patients and control subjects


SBP (mmHg) 1312 plusmn 118 1196 plusmn 107 lt0001lowastlowast

DBP (mmHg) 821 plusmn 82 777 plusmn 68 lt0001lowastlowast

EA ratio 104 plusmn 027 124 plusmn 025 lt0001lowastlowast

DCT (ms) 2128 plusmn 598 1988 plusmn 575 0103Peak E MV (ms) 074 plusmn 015 079 plusmn 013 0018lowast

Peak A MV (ms) 076 plusmn 015 068 plusmn 013 lt0001lowastlowast

IVRT (ms) 903 plusmn 118 859 plusmn 65 lt0001lowastlowast

MVFP (cms) 0043 plusmn 0020 0032 plusmn 0015 lt0001lowastlowast

S1015840Lm (cms) 930 plusmn 260 1031 plusmn 214 0005lowastlowast

E1015840Lm (cms) 1028 plusmn 302 1372 plusmn 307 lt0001lowastlowast

A1015840Lm (cms) 1043 plusmn 251 994 plusmn 257 0183S1015840Sm (cms) 843 plusmn 175 881 plusmn 145 0115E1015840Sm (cms) 861 plusmn 240 1083 plusmn 244 lt0001lowastlowast

A1015840Sm (cms) 1021 plusmn 226 1009 plusmn 229 0708Results are presented as mean plusmn SDSBP systolic blood pressure DBP diastolic blood pressure DCT deceleration time MV mitral valve IVRT isovolumic relaxation time MVFP mitral valveflow propagation S1015840LM tissue Doppler derived S1015840 amplitude of lateral part at mitral valve E1015840Lm tissue Doppler derived E1015840 amplitude of lateral part at mitralvalve A1015840Lm tissue Doppler derived A1015840 amplitude of lateral part at mitral valve S1015840Sm tissue Doppler derived S1015840 amplitude of septal part at mitral valve E1015840Smtissue Doppler derived E1015840 amplitude of septal part at mitral valve A1015840Sm tissue Doppler derived A1015840 amplitude of septal part at mitral valvelowastlowastMeans high significant lowastmeans significant

33 Transmitral and Tissue Doppler Imaging The 119864119860 ratioand the peak 119864 wave at mitral flow were lower and the peak119860 wave at mitral flow was higher in OSA patients comparedwith control subjects IVRT and MVFP were significantlylonger in OSA patients compared to the controls TissueDoppler derived 1198781015840 amplitude of lateral part at mitral valve(1198781015840Lm) and1198641015840 wave amplitudes both at the lateral (1198641015840Lm) andseptal part of the mitral valve (1198641015840Sm) were significantly lowerin OSA patients compared to controls However althoughthe amplitude of the 1198781015840 of the mitral part of the mitral valve(1198781015840Sm) was also lower in OSA patients compared to controlsthe difference was not significant (Table 4)

34 Multivariate Analysis for Tissue Doppler LV ParametersMultivariate linear regression analysis revealed that presenceof OSA was independently associated with the decreased

values of 1198781015840Lm and 1198641015840Lm even after adjustment for hyper-tension and decreased values of 1198641015840Lm and 1198641015840Sm even afteradjustments for hypertension and BMI as well as after theadjustments for all possible bias (hypertension BMI gendertriglycerides HDL and LDL) (Table 5)

4 Discussion

The data in our cross-sectional study indicate impairedLV diastolic relaxation as well as impaired LV longitudinalsystolic function in patients with newly diagnosed OSAand normal left ventricle ejection fraction Several previousstudies have shown that OSA is frequently accompaniedwith diastolic dysfunction [5ndash7] However patients withOSA have multiple cardiovascular risk factors and coexistingdisorders that influence diastolic dysfunction such as ageing


Table 5 Multivariate regression analysis for tissue Doppler LV parameters

Adjustment S1015840Lm E1015840Lm A1015840Lm S1015840Sm E1015840Sm A1015840SmStandard 120573 (119875 value)

No adjustment minus0198 (0005)lowastlowast minus0483 (lt0001)lowastlowast 0094 (0183) minus0111 (0115) minus0410 (lt0001)lowastlowast 0026 (0708)Gender minus0260 (lt0001)lowastlowast minus0495 (lt0001)lowastlowast 0076 (0301) minus0162 (0025)lowast minus0398 (lt0001)lowastlowast minus0016 (0827)HTA minus0223 (0006)lowastlowast minus0405 (lt0001)lowastlowast 0074 (0363) minus0124 (0129) minus0367 (lt0001)lowastlowast 0003 (0974)HTA BMI minus0167 (0059) minus0390 (lt0001)lowastlowast 0093 (0302) minus0140 (0120) minus0395 (lt0001)lowastlowast 0025 (0783)HTA BMI and gender minus0232 (0008)lowastlowast minus0401 (lt0001)lowastlowast 0074 (0421) minus0186 (0041)lowast minus0381 (lt0001)lowastlowast minus0018 (0841)HTABMI gender andTg minus0225 (0012)lowast minus0402 (lt0001)lowastlowast 0051 (0508) minus0179 (0053) minus0374 (lt0001)lowastlowast minus0018 (0845)

HTA BMI gender TgHDL and LDL minus0230 (0009)lowastlowast minus0408 (lt0001)lowastlowast 0064 (0494) minus0180 (0051) minus0375 (lt0001)lowastlowast minus0017 (0855)

S1015840LM tissue Doppler derived S1015840 amplitude of lateral part at mitral valve E1015840Lm tissue Doppler derived E1015840 amplitude of lateral part at mitral valve A1015840Lmtissue Doppler derived A1015840 amplitude of lateral part at mitral valve S1015840Sm tissue Doppler derived S1015840 amplitude of septal part at mitral valve E1015840Sm tissueDoppler derived E1015840 amplitude of septal part at mitral valve A1015840Sm tissue Doppler derived A1015840 amplitude of septal part at mitral valve HTA hypertension Tgtriglycerides HDL high density lipoproteins LDL low density lipoproteins BMI body mass indexlowastlowastMeans high significant lowastmeans significant

obesity gender hypertension triglycerides HDL LDL anddiabetes That was the reason we have done adjustments toBMI hypertension LDL HDL gender and triglycerides inpatients with OSA trying to overcome these bias Diabeticswere not enrolled in the study Few studies have also shownthat OSA per se independently impairs LV diastolic functionregardless of obesity and hypertension [17ndash19]

The present study demonstrated that OSA in newlydiagnosed patients independently affected both LV regionalsystolic and diastolic functions Controversy exists regardingLV global and regional systolic function in OSA Accordingto the previous data there is a higher proportion of heartfailure in patients with OSA compared to general populationHowever most of them have normal ejection fraction despitesigns of the heart failure [20 21] Previous TDI studieshave added additional data and demonstrated that OSA isaccompanied by subclinical LV dysfunction in OSA patients[22 23] Altekin et al [24] have also shown on a smaller groupof patients with OSA but not newly diagnosed using speckletracking echocardiography that in the early stages of OSAlongitudinal systolic LV dysfunction is detected in additionto the diastolic dysfunction In our study newly diagnosedpatients with OSA were enrolled but since most of themhad moderate and severe OSA they certainly were not at thebeginning of disease

Impairment of the longitudinal left ventricle functiondespite normal LV ejection fraction in patients with newlydiagnosed OSA has serious implications longitudinal fiberswhich are subendocardially located are more susceptible tomyocardial ischemia caused by the apnea-hypopnea episodesof the OSA Normal ejection fraction is due to compensatoryunchanged normal radial LV function An increased LVwall tension and preload caused by the OSA lead to LVlongitudinal systolic dysfunction and increased myocardialwall thickness is the consequence of the compensatorymech-anism aiming at decreasing LV wall tension and protectingmyocardial function

As the LV hypertrophy and concentric remodelingprogress the subendocardial myocardial layer responsiblefor the longitudinal shortening becomes more susceptibleto ischemic apoptosis and fibrous phenomena resulting inreduced LV longitudinal shortening in the early stages of theOSA Depressed myocardial contractile reserve in patientswith obstructive sleep apnea was also proven by dobutaminestress echocardiography supporting this pathophysiologicalrationale [25] Several pathophysiological mechanism suchas LV concentric hypertrophy activated sympathetic nerveactivity and elevated central blood pressure have beenproposed as the additional mechanisms of the LV diastolicdysfunction but the present study demonstrated that newlydiagnosed moderate to severe OSA impaired LV diastolicfunction independently of these suggested mechanisms Fur-thermore the study clearly showed that patients with newlydiagnosed OSA besides impaired LV diastolic function havealso impaired left ventricle longitudinal systolic functionalthough they still have normal LV ejection fraction

5 Limitations

The study has some limitations Although patients andcontrol subjects were age matched significant differences ofprevalence of coronary risk factors and body mass indexbetween the two groups may have an impact on the leftventricular dysfunction Thus the early screening for coro-nary artery disease in OSA patients should be mandatorySecond although OSA patients had severe degree of thedisease the real duration of the process could not be preciselydetermined

However the strength of the present study is twofoldFirst this is the first echocardiographic study in OSA patientsin Serbian population and in the same time one of thelargest echocardiographic studies in OSA patients in generalSecond adjustments of echocardiographic parameters toBMI and hypertension have been successfully done


6 Learning Points

(i) The study revealed that a greatest proportion ofpatients with newly diagnosed OSA has severe gradeof OSA

(ii) In newly diagnosed patients with OSA with normalleft ventricle ejection fraction left ventricular func-tion is severely impaired both diastolic and systolic

(iii) There is a strong correlation between OSA andimpaired left ventricle diastolic and regional systolicfunction even after adjustments to hypertensionand BMI identifying OSA as an independent riskfactor for early left ventricular diastolic and systolicdysfunction

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

This study is a part of the Scientific Project no OI 173022supported by the Ministry of Science Serbia

References

[1] C Fuhrman B Fleury X L Nguyen and M C DelmasldquoSymptoms of sleep apnea syndrome high prevalence andunderdiagnosis in the French populationrdquo Sleep Medicine vol13 no 7 pp 852ndash858 2012

[2] M RMannarino F Di Filippo andM Pirro ldquoObstructive sleepapnea syndromerdquoEuropean Journal of InternalMedicine vol 23no 7 pp 586ndash593 2012

[3] W B Leong T Arora D Jenkinson et al ldquoThe prevalence andseverity of obstructive sleep apnea in severe obesity the impactof ethnicityrdquo Journal of Clinical Sleep Medicine vol 9 no 9 pp853ndash858 2013

[4] J Rich A Raviv N Raviv and S E Brietzke ldquoAll-causemortality and obstructive sleep apnea severity revisitedrdquoOtolaryngologymdashHead andNeck Surgery vol 147 no 3 pp 583ndash587 2012

[5] C Zamarron L Valdes Cuadrado and R Alvarez-Sala ldquoPatho-physiologic mechanisms of cardiovascular disease in obstruc-tive sleep apnea syndromerdquo Pulmonary Medicine vol 2013Article ID 521087 16 pages 2013

[6] X Ge F Han Y Huang et al ldquoIs obstructive sleep apneaassociated with cardiovascular and all-cause mortalityrdquo PLoSONE vol 8 no 7 Article ID e69432 2013

[7] M Butt G Dwivedi A Shantsila O A Khair and G Y LipldquoLeft ventricular systolic and diastolic function in obstructivesleep apnea impact of continuous positive airway pressuretherapyrdquo Circulation Heart Failure vol 5 no 2 pp 226ndash2332012

[8] Y Usui Y Takata Y Inoue et al ldquoSevere obstructive sleep apneaimpairs left ventricular diastolic function in non-obese menrdquoSleep Medicine vol 14 no 2 pp 155ndash159 2013

[9] RWachter L Luthje D Klemmstein et al ldquoImpact of obstruc-tive sleep apnoea on diastolic functionrdquo European RespiratoryJournal vol 41 no 2 pp 376ndash383 2013

[10] M Meier and S Andreas ldquoMechanisms of cardiovascular co-morbidity in patients with obstructive sleep apnoea syndromerdquoPneumologie vol 66 no 11 pp 650ndash657 2012

[11] M Murri R Garcıa-Delgado J Alcazar-Ramırez et al ldquoEffectof CPAPonoxidative stress and circulating progenitor cell levelsin sleep patients with apnea-hypopnea syndromerdquo RespiratoryCare vol 56 no 11 pp 1830ndash1836 2011

[12] C H Won H J Chun S M Chandra P S Sarinas R KChitkara andPAHeidenreich ldquoSevere obstructive sleep apneaincreases mortality in patients with ischemic heart disease andmyocardial injuryrdquo Sleep and Breathing vol 17 no 1 pp 85ndash912013

[13] Y Usui H Tomiyama H Hashimoto et al ldquoPlasma B-typenatriuretic peptide level is associated with left ventricularhypertrophy among obstructive sleep apnoea patientsrdquo Journalof Hypertension vol 26 no 1 pp 117ndash123 2008

[14] The Report of an American Academy of Sleep Medicine TaskForce ldquoSleep-related breathing disorders in adults recommen-dations for syndrome definition and measurement techniquesin clinical researchrdquo Sleep vol 22 no 5 pp 667ndash689 1999

[15] R B Devereux ldquoDetection of left ventricular hypertrophy byM-mode echocardiography Anatomic validation standardiza-tion and comparison to other methodsrdquo Hypertension vol 9no 2 pp II19ndashII26 1987

[16] MGalderisiM YHenein J Dhooge et al ldquoRecommendationsof the European association of echocardiography how to useecho-doppler in clinical trials different modalities for differentpurposesrdquo European Journal of Echocardiography vol 12 no 5pp 339ndash353 2011

[17] S M Kim K I Cho J H Kwon H G Lee and T I KimldquoImpact of obstructive sleep apnea on left atrial functional andstructural remodeling beyond obesityrdquo Journal of Cardiologyvol 60 no 6 pp 475ndash483 2012

[18] K I Cho J H Kwon S M Kim T J Park H G Lee andT I Kim ldquoImpact of obstructive sleep apnea on the globalmyocardial performance beyond obesityrdquo Echocardiographyvol 29 no 9 pp 1071ndash1080 2012

[19] Y Usui Y Takata Y Inoue et al ldquoCoexistence of obstructivesleep apnoea and metabolic syndrome is independently asso-ciated with left ventricular hypertrophy and diastolic dysfunc-tionrdquo Sleep and Breathing vol 16 no 3 pp 677ndash684 2012

[20] E Varol S Akcay M Ozaydin O Ozturk S S Cerci and USahin ldquoInfluence of obstructive sleep apnea on left ventricularmass and global function sleep apnea and myocardial perfor-mance indexrdquo Heart and Vessels vol 25 no 5 pp 400ndash4042010

[21] M A Arias F Garcıa-Rıo A Alonso-Fernandez O MedianoIMartınez and J Villamor ldquoObstructive sleep apnea syndromeaffects left ventricular diastolic function effects of nasal contin-uous positive airway pressure in menrdquo Circulation vol 112 no3 pp 375ndash383 2005

[22] T Nishikage H Nakai R M Lang and M Takeuchi ldquoSub-clinical left ventricular longitudinal systolic dysfunction inhypertension with no evidence of heart failurerdquo CirculationJournal vol 72 no 2 pp 189ndash194 2008

[23] H A Kasikcioglu L Karasulu Z Tartan E Kasikcioglu CCuhadaroglu and N Cam ldquoOccult cardiac dysfunction inpatients with obstructive sleep apnea syndrome revealed bytissue Doppler imagingrdquo International Journal of Cardiologyvol 118 no 2 pp 203ndash205 2007


[24] R E Altekin A Yanikoglu A O Baktir et al ldquoAssessmentof subclinical left ventricular dysfunction in obstructive sleepapnea patients with speckle tracking echocardiographyrdquo TheInternational Journal of Cardiovascular Imaging vol 28 no 8pp 1917ndash1930 2012

[25] N Okuda T Ito N Emura et al ldquoDepressed myocardialcontractile reserve in patients with obstructive sleep apneaassessed by tissue doppler imaging with dobutamine stressechocardiographyrdquo Chest vol 131 no 4 pp 1082ndash1089 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


LVEF does not always mean normal LV systolic functionOn the other hand diastolic function is often impaired inOSA [7ndash9] Myocardial ischemia and oxidative stress are thepathophysiological explanations of these disturbances [1011] Left ventricular systolic function is generated by radialand longitudinal shortening and both processes are veryimportant Radial shortening is predominantly dependent onthe contraction of circumferential myocardial fibres in themidwall more resistant to ischemia However longitudinalshortening is generated by both longitudinal subendocardialand subepicardial fibres where subendocardium is morevulnerable tomyocardial ischaemia Hence assessment of LVlongitudinal function might be a sensitive marker for detect-ing subclinical alterations in LV systolic performance andthe early detection of the left ventricular systolic dysfunction[7 12]

Mitral annular velocity evaluated by tissue Dopplerimaging (TDI) is a sensitive marker of the LV longitudinaldysfunction We assumed that early left ventricular systolicand diastolic dysfunctions are present in patients with newlydiagnosed OSA even when left ventricle ejection fraction isnormal Thus the aim of the study was to evaluate whetherobstructive sleep apnea (OSA) contributes directly to leftventricular (LV) diastolic and regional systolic dysfunctionin newly diagnosed OSA with normal left ventricle ejectionfraction

2 Materials and Methods

21 Design and Settings A total of 792 consecutive patientswho had undergone overnight polysomnography (PSG) withnewly diagnosed OSA at the Center for Sleep MedicineBezanijska kosa from January 2011 to January 2013 wereenrolled in the study Among them the patients who met thefollowing conditions that might have had an influence on theresults of echocardiographic parameters were excluded (1)central sleep apnoea (2) history of coronary artery diseaseor electrocardiographic changes suggestive of myocardialinfarction (3) proved myocardial ischaemia at the ergometrytesting (4) global LV systolic dysfunction (LVEF lt 50) ora history of congestive heart failure (5) diabetes mellitus(6) moderate to severe valvular heart diseases (7) hyper-trophic cardiomyopathy (8) history of chronic obstructivepulmonary disease or asthma (9) atrial fibrillation (10)previous diagnosis of OSA andor the previous use of con-tinuous positive airway pressure therapy and (11) chronicrenal impairment (serum creatinine more than 112 120583molL)including chronic hemodialysis patients who did not haveOSA (ie lt5 eventsh of apnea hypopnea index (AHI))All patients had complained of daytime sleepiness andorloud snoring The investigation was done to the principlesenumerated in theHelsinki Declaration of 1975 and informedconsent was obtained after full explanation of the procedureFinally 125 patients (mean age 58plusmn11 years minimal 21 andmaximal 75) were enrolled in the study

In addition a total of age matched 78 asymptomatichealthy subjects who did not have any cardiovascular andrespiratory symptoms volunteer to participate in study were

enrolled in study as a control group All participants from thecontrol group had neither hypertension nor coronary arterydisease and all had normal ergometry testing and normalarterial tension during three repeated measurements

All patients had undergone overnight polysomnographyto determine the presence and severity of OSA Completetransthoracic echocardiogram had been also performed nextmorning The two investigated groups were age matchedconsidering aging bias in left ventricle diastolic dysfunctionThe study protocol was approved by the Ethics Committee ofUniversity of Belgrade and all subjects gave written informedconsent for the enrollment

22 Sleep Study Overnight fully attended PSG monitoringwas performed with the Alice 4 Sleep System (RespironicsInc Murrysville PA USA) in the referral Center for SleepMedicine using standard recording techniques and preciseprotocol of PSG monitoring [13] Surface electrodes wereapplied to perform electroencephalogram chin electromyo-gram electrocardiogram and electrooculography Airflowwasmonitored using an air pressure sensor placed at the noseand thermistor placed at the nose and mouth and arterialoxygen saturation (SaO

2) was recorded continuously with a

pulse oximeter Apnea was defined as the disappearance ofairflow for over 10 s hypopneawas defined as a 50or greaterdecrease in airflow lasting for more than 10 s associatedwith arousal or a 3 or greater decrease in arterial oxygensaturation from the baseline level The AHI was calculated asthe total number of apnea and hypopnea episodes per hourof sleep According to the AHI the patient was classifiedas having OSA when the obstructive component was over5 events per hour Severe OSA was classifies as AHI gt 30eventsh [14]

23 Standard Echocardiography Echocardiography was per-formed in the left lateral decubitus position with a commer-cially available ultrasound machine (Vivid VII GE Health-care Milwaukee WI USA) and 3S-RS (35MHz) probeAll images were obtained from standard parasternal andapical position using 2D M-mode and Doppler echocar-diographic techniques All examinations were performed byan experienced cardiologist who was blind for the resultsof polysomnography The LV end-diastolic and end-systolicdimensions as well as interventricular septum and posteriorwall thicknesses were obtained from M-mode echocardio-graphy [15] LVEF was measured using biplane Simpsonrsquosmethod according to the recommendation of EuropeanAsso-ciation for Echocardiography [16] Right ventricle dimension(RV) and right ventricular fractional area change (FAC RV)were also measured

Pulse Doppler sample volume was placed at the mitralvalve tips in the apical four-chamber view to record LV inflowvelocity From LV inflow velocity early diastolic peak flowvelocity (119864) late diastolic peak flow velocity (119860) 119864119860 ratioand deceleration time of the 119864 wave velocity were measuredand then calculated from three consecutive cardiac cycles[15] Isovolumic contraction and relaxation times were alsocalculated from LV inflow and outflow tract velocities [16]











Low HDL (119899 ) 35 (280) 11 (141) 0021lowast


Smoking (119899 ) 45 (360) 16 (205) 0019lowast





3 Results



































4 Discussion












5 Limitations




6 Learning Points






Acknowledgment


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























Low HDL (119899 ) 35 (280) 11 (141) 0021lowast


Smoking (119899 ) 45 (360) 16 (205) 0019lowast





3 Results



































4 Discussion












5 Limitations




6 Learning Points






Acknowledgment


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of










































4 Discussion












5 Limitations




6 Learning Points






Acknowledgment


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























5 Limitations




6 Learning Points






Acknowledgment


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















6 Learning Points






Acknowledgment


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















research article early left ventricular systolic and...

Documents