ULTRASONOGRAFIA DOPPLER A ULTRASONOGRAFIA DOPPLER A ARTEREI BRAHIALE IN ARTEREI BRAHIALE IN

EVALUAREA PACIENTULUI EVALUAREA PACIENTULUI HIPERTENSIVHIPERTENSIV

Alexandru AndritoiuAlexandru Andritoiu

SCUM CraiovaSCUM Craiova

ABAB

• Locul de masurare a TALocul de masurare a TA• TA periferica vs TA centrala?TA periferica vs TA centrala?• Evaluarea US – recentaEvaluarea US – recenta• Scop de cercetare fiziologicaScop de cercetare fiziologica

TehnicaTehnica

• B-scanB-scan• Color Doppler USColor Doppler US• Power-angioPower-angio• Spectral analysisSpectral analysis

Remodelarea ABRemodelarea AB

• ADAPTATIVAHTA• Obezitate• Hiper-Col• ATS

• MALADAPTATIVA• imbatranirea

Chung WB et al. Arterioscl Thromb Vasc Biol 2009

Rol compensator!

Cauze de remodelareCauze de remodelare

PatologicePatologice• HTA• Ateroscleroza (placi)• Hipercolesterolemie• Diabet zaharat• Obezitate • Sdr. Metabolic• Uremie-dializa

FiziologiceFiziologice• Antrenament fizic• Imbatranirea

Remodelarea AB in HTARemodelarea AB in HTA

• Proces compensator/adaptativ

• Prezervarea D/A luminale

• Shear-stress mentinut la un nivel scazut

Modificarile morfologiceModificarile morfologice

Cresterea D si A• Mecanism adaptativ (proces compensator)• Semn de ATS• Marker de risc CV• Relatia cu ATS carotidiana, BOAP

Grosimea peretelui ABGrosimea peretelui AB

Simon A CH, Safar ME - Br J Cl Pharmac 1984;18:243-246

Brachial artery haemodynamics in arterial hypertension

D creste in HTAD creste in HTA

• Normotensivi (N=25)

D = 3.2+/-0.2 mm• HTA (N=32)

D = 4.1+/0.2 mm

p <0.001

D = 4.2 mm

Andritoiu A 2000

D = 3.5 mm

NormoTA

HTA

Diametrul AB - Diametrul AB - relatia cu FR-CVrelatia cu FR-CV

Holubkov R et al. Am Heart J 143(5):802-807, 2002

Ultrasound image of the brachial artery (longitudinally) at 8× magnification, 11-MHz transducer frequency annotated for anatomic landmarks.

Grosimea peretelui ABGrosimea peretelui AB

Profilul anvelopei spectraleProfilul anvelopei spectrale

Profilul fiziologic trifazic

,,de rezistivitate crescuta,,

1

2

3 4

Parametrii spectraliParametrii spectrali

• S• D• Vmean• TAMx• IP• IR• Q (ml/min)

Modificari spectrale in HTAModificari spectrale in HTA

• Largirea spectrala• Atenuarea undei

reflectate• Disparitia ferestrei

spectrale• Unda tele-sistolica

Spectral Spectral broadening broadening

gradinggrading

(A) 1 p.

(B) 2 p.

(C) 3 p.

A

B

CAndritoiu A, 2008

Modificarile anvelopei spectrale la o pacienta in varsta de 51 ani,cu HTA si hipercolesterolemie:

disparitia ferestrei spectrale, largirea spectrala, cu pastrarea profilului trifazic, cu atenuarea undelor reflectate.

D = 3.6 mm (normal)

Modificari functionaleModificari functionale

%FMD – tonusul vasomotorVasodilatatia:• Mediata de endoteliu (Acetilcolina, metacolina)• Independenta de endoteliu (nitroprusiat, NTG-sl)• Mediata de flux (compresie)

Vascular Health and Risk management 2008;4(3);647-652

Cardiovascular Risk Factors Hypercholesterolemia Atherosclerosis Type I and II diabetes mellitus and

insulin resistance Male sex Smoking Systemic hypertensionSystemic hypertension Family history of CAD Homocysteine concentrations Aging Postmenopausal Hypertriglyceridemia Chronic Infections/Inflammation Vasculitic conditions C-reactive protein concentrations Herpes viruses Cytomegaloviruses Chlamydia pneumoniae and

Helicobacter pylori

Disease-based Conditions Chagas disease Post-Kawasaki disease Pulmonary hypertension Heart failure and dilated

cardiomyopathy Syndrome X and variant

angina Transplantation

atherosclerosis End-stage renal disease Miscellaneous conditions Pregnancy-induced

hypertension/preeclampsia Methionine loading Mental stress Environmental Factors Passive smoking Turbulent vessel flow Oxidants

Conditions Associated With Impairment in Conditions Associated With Impairment in

Endothelium-dependent VasodilationEndothelium-dependent Vasodilation

Kevin M. Sowinsk - Medscape Pharmacists 2000

Disfunctia endoteliala (AB)Disfunctia endoteliala (AB)

• Relatie cu FR-CV• Relatie cu BCI• Relatie cu ATS carotidiana• Relatie cu IxGB• Relatie cu D-AB

Risk factors and ET dysfunction

• Importance of risk factors and endothelial dysfunction in early life for atherosclerosis development and later cardiovascular outcome.

• A) Impact of cardiovascular risk factor profile at age 50 years on subsequent clinical events in the Framingham Study.

• B) Association between risk factors and carotid IMT in young adults with enhanced, intermediate, and reduced FMD in the Cardiovascular Risk in Young Finns Study.

Lloyd-Jones et al. 2006; Juonala et al. 2004

Evaluation of Brachial Artery reactivity (%FMD)

US• B-mode (high-frequency)

• CD-US• PWD-US

Endothelial function, defined as flow mediated dilatation (FMD), is estimated as the percentage increase in vessel diameter from baseline conditions to maximum vessel diameter during hyperemia.

Celermajer et al 1994

Probe position in relation to cuffProbe position in relation to cuff

Schematic drawing of ultrasound imaging of the brachial artery with upper versus lower cuff placement and transducer position above the antecubital fossa. BP = blood pressure; FMD = flow-mediated vasodilation.

Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of

the FMD measurement on the FMD response Michiel L. Bots, J. Westerink, TJ Rabelink, E.J.P. de Koning

Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of

the FMD measurement on the FMD response Michiel L. Bots, J. Westerink, TJ Rabelink, E.J.P. de Koning

• The lower arm occlusion compared with upper arm occlusion was related to a significantly decreased FMD (mean difference in FMD –2.47%; 95% CI 0.55–4.39).

• An occlusion duration of 4.5 min was related to a significantly increased FMD compared with an occlusion time of 4 min (mean difference 1.30%; 95% CI 0.35–2.46).

Bots ML et al. Eur Heart J 2004

The unsolved issue is the broad spectrum of %FMD reference value

-1.9 – 19.2!?!

Bots ML et al. Eur Heart J 2004

4 min

Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated

vasodilation of the brachial artery

A report of the International Brachial Artery Reactivity Task Force Mary C. CorrettiMary C. Corretti, Todd J. Anderson, Emelia J. Benjamin, David Celermajer, Francois Charbonneau, Mark A. Creager, John Deanfield, Helmut Drexler,

Marie Gerhard-Herman, David Herrington, Patrick Vallance, Joseph Vita, and Robert Vogel

JACC 2002; 39:257-265

Representative flow-mediated response of brachial artery

(forearm occlusion)

1) baseline diameter (DBL), 2) maximum diameter after cuff release (Dmax) 3) diameter 3 minutes after cuff release, 4) time of maximum diameter after cuff release.

. The FMD was determined with the occlusion cuff on the upper arm . Images of the brachial artery were digitized (one image/cardiac cycle on the R-wave) at baseline (Pre) and continuously for 2 min beginning 20 s after cuff release using a commercially available image acquisition system (CVI Acquisition, Information Integrity, Stow, Massachusetts). Brachial artery diameters were measured using an automated edge-detection system (Brachial Tools, Medical Imaging Applications, Iowa City, Iowa).

Time course of brachial artery flow-mediated Time course of brachial artery flow-mediated vasodilation (FMD) in a healthy individualvasodilation (FMD) in a healthy individual

Peak percentage change in brachial artery diameter post-reactive hyperemia

Vasoactive substances

• Ach• NTG

Mechanical stress• Forearm ischemia

induced 4 min. by an occluding cuff

Peak vs Total hyperemia ?

Pyke KE et al. Appl Physiol 2007

30 sec 60 sec 180 sec

Flow-Mediated VasodilationA Diagnostic Instrument, or

an Experimental Tool?

Disfunctia endoteliala in HTADisfunctia endoteliala in HTA

• %FMD nu se coreleaza cu TA –cab

• %FMD se coreleaza cu TAM-24 ore (ABPM)

• %FMD nu se coreleaza cu profilul circadian (dipper/non-dipper)

• Nu se coreleaza cu IxMVS sau cu pattern-ul HVS

Rizzoni D 1998, Gomez C 2002, Andritoiu A 2004, Muiesan L 2004

Relatia %FMD –TOD in HTARelatia %FMD –TOD in HTA

11.88

10

7.376.85

NonTOD 1TOD 2TOD 3TOD

Xu J et al. J Hum Hypertens 2009

FMD%

• The most significant determinant of FMD was basal brachial artery diameter. • Greater basal diameter is associated with worse FMD.

HTA – fenotipuri hemodinamice HTA – fenotipuri hemodinamice diferitediferite

• HTA la tanarHTA la tanar• HTA primaraHTA primara• HTA sistolica izolataHTA sistolica izolata• Preeclampsie Preeclampsie • WC-HTWC-HT

%FMD in WCH vs SEH

SEH – HT sustinuta WCH – HT de halat alb

Gómez-Cerezo J et al. Hypertension. 2002;40:304

HTA la varstniciHTA la varstnici

%FMD%FMD• Scade la varstnici• Scade in HTA• Relatie cu rigidizarea peretelui arterial

Saka B et al. Arch Gerontol Geriatr 2005

Parker PA et al. Am J Physiol Heart Circ Physiol, 2006

Variatia circadiana a %FMD in HTAVariatia circadiana a %FMD in HTA

2.22

4.284.37

7 12 21

%FMD

Orele

Kollias GE J Hum Hypertens 2009

Relationship Between Carotid Artery Intima-Media Thickness and Brachial

Artery Flow-Mediated Dilation in Middle-Aged Healthy Men

R.T. Yan, T.J. Anderson, F. Charbonneau, L. Title, S. Verma, E. Lonn, on behalf of the FATE Investigators

 

Yan RT et al- JACC 2005

• Carotid IMTCarotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. • Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. • The relationship between carotid IMT and brachial artery FMD has not been well studied.

Correlation between Flow-Mediated Vasodilatation of the Brachial Artery and

Inima-Media Thickness in the Carotid Artery in Men

• 34 M with ATS vs controls• 61+/- 2 yr• B-mode US

%FMD

CIMT

5.1+/-0.6%

2.8+/-0.4%

ATS Control

Hashimoto M et al. Arteriosclerosis, Thrombosis and Vascular Biology 1999

P<0.01

%FMD showed a significant negative correlation with IMT of CCA

%FMD

Relatia CIM ACC-%FMDRelatia CIM ACC-%FMD

Yan RT et al. J Am Coll Cardiol, 2005; 45:1980-1986

%FMD – CIMT - PWV%FMD – CIMT - PWV

135 pts• 110 pts - CVRFs• 33 pts. -CAD,

stroke, PADMETHODo USo CIMT/plaqueso BA-FMD%o PWV (brachial-ankle)

• All measurements are related each other !

• All measurements had a markedly higher prevalence of ATS disease and carotid plaques !

• The combination of these The combination of these measurements will be of measurements will be of stronger clinical stronger clinical relevance !relevance !

Kobayashi K et al. Atherosclerosis 2004

Caz clinicCaz clinic

• MV, 51y, F• HTA• LDL-Col 167 mg/dl• Non - Carotid ATS • FMD = 9%

Caz clinicCaz clinic

• NE, 56y, F• Hiper-CT• HTA• Car ATS 2/6• FMD =12%

AB-largirea anvelopei spectrale

Caz clinicCaz clinic

• AI, 52y, M• Fumator• Hiper-CT• HTA• Car-ATS 3/6• FMD = 6.6%

Relatia AB cu CIMT

• Mean CIMT - CA ATS stage r = 0.74; p<0.001• Max CIMT - CA ATS stage r = 0.51; p<0.01• Mean CIMT - BA area r = 0.40; p<0.05• Max CIMT - BA area r = 0.32; p<0.05• BA area - CA ATS stage r = 0.47; p<0.01• BA TAMx - BA spectral-broad. score r = 0.73; p<0.001• BA TAV - BA spectral-broad. score r = 0.66; p<0.001

Andritoiu A, 2008

%FMD in predictia HTA%FMD in predictia HTA

• Studiu de cohorta• 3.500 subiecti• 4.8 yr• 31.3% au dezvoltat

HTA

• Relatia dintre %FMD si aparitia HTA nu a fost semnificativa !

• Alterarea functiei endoteliale nu joaca un rol crucial in aparitia HTA !

Hiperemia reactiva (%FMD)Hiperemia reactiva (%FMD) este predictor de PE ! este predictor de PE !

1.6+/-1

11+/-4.5

0

2

4

6

8

10

12

PE Norm

Takase B et al. J Hum Hypertens 2003

• Sb 88%• Sp 93%• VPP 84%• VPN 94.8%

• %FMD sapt 18-24 • predictor precoce

HTA si MenopauzaHTA si Menopauza

• Studiu de cohorta• N = 952 • Follow-up 3.6+/0.7 yr• 112 pts dezv HTA

%FMD <3.5

RR = 5.77 (4.38-8.10)

Alterarea functiei vasomotorii endoteliale are valoare predictiva in aparitia HTA la femeile in post-menopauza

Rossi R et al. JACC 2004

%FMD-relatia cu varsta

Average brachial and popliteal responses to nitroglycerin (NTG) in young and older subjects.

Dilation was calculated as percent change from pre-NTG diameter to maximum diameter measured during the 10 min following NTG administration. Values are means

± SE. *Significantly different from young (P < 0.05).

Parker PA et al. Am J Physiol Heart Circ Physiol 291: H3043-H3049, 2006

AB - tinta terapeutica?AB - tinta terapeutica?

• Remodelarea arteriala

• Imbunatatirea functiei endoteliale

• Imbunatatirea proprietatilor peretelui arterial

ObiectiveObiective

AntihipertensiveEfecte terapeutice

• IECA• Sartani• Ca-antag.• Diuretice• Beta-bloc

End (++), Remod (++)

End (+/-), Remod (+/-)

End(+), Remod (++)

End (-), Remod (-)

End(+/-), Remod (-)

Gokce, N. et al. J Am Coll Cardiol 2002;40:761-765

The acute effect of a single oral dose of vasoactive medication on systolic blood pressure (SBP) (mm Hg) and absolute percent change in brachial artery flow-mediated (FMD) and

nitroglycerin-mediated dilation (NMD) in normal subjects (3 hrs)in normal subjects (3 hrs)

TAS (mmHg)

FMD%

Modificarile Modificarile FMDFMD--AAB dupa 6-12 luni de B dupa 6-12 luni de terapie antihipertensivaterapie antihipertensiva

(nifedipina) – 58 pacienti

Muiesan ML et col. Hypertension 1999;33:575-580

%FMD - Carvedilol

Matsuda Y et al. Am Heart J 140(5):753-759, 2000

5.1% ± 0.5% at baseline to 7.8% ± 0.5%; p < .05

Flow mediated post-ischemic endothelium-dependent vasodilatation expressed as percent increase in arterial diameter (mean ± SD) with respect to baseline values in

hypercholesterolemic coronary artery disease patients under the effects of the statin Simvastatin and the ECA inhibitor Enalapril, either separately or combined.

E: Enalapril, GI: Group I, GII: Group II, S: Simvastatin. * p < 0.001 vs baseline, ‡ p < 0.01 vs Baseline, † p < 0.05 vs 8 weeks, § p < 0.001 vs 8 weeks.

Esper et al. Cardiovascular Diabetology 2006 5:4  

Studii personaleStudii personale

• Comportamentul vasoactiv al arterei brahiale pa pacientii hipertensivi-studiu comparativ Eco-Doppler. Al 39-Lea Cong. Nat Cardiol, Sinaia (Premiul Soc. Rom. Cardiologie), 2000

• Vasoactive behaviour of brachyal artery in hypertensive patients. The 5th Cong BMMC, Ankara, 2000

• Ateroscleroza carotidiana si relatia cu profilul spectral al arterei brahiale. Al 40-lea Cong Nat Craiologie, Sinaia, 2001

• Brachial artery. Ultrasound evaluation and Brachial artery. Ultrasound evaluation and clinical utilityclinical utility.. Conf SRUMB, Timisoara 2009

MESAJEMESAJE

• La un pacient hipertensiv, nu limita examinarea doar la masurarea TA (AB) !

• Aplicarea transductorului la nivelul AB poate sa ofere informatii noi, nebanuite, ce pot modifica esential managementul pacientului (incadrarea intr-un grad superior de RCV) !

• Modificarile anvelopei spectrale AB pot fi asociate ATS arterelor mari – marker surogat de ATS !

• Examinarea US a AB va fi asociata examinarii arterelor mari (Car, Fem) !