This document discusses the remodeling of the brachial artery (AB) in arterial hypertension (HTA). It covers the following key points: 1. AB remodeling in HTA can be adaptive/compensatory (increasing diameter and wall thickness to maintain luminal area) or maladaptive. Imaging techniques like ultrasound can evaluate AB morphology and function. 2. Spectral Doppler analysis of AB blood flow shows broadening of the spectral envelope in HTA, reflecting increased arterial stiffness. Flow-mediated dilation (%FMD) evaluates endothelial function. Lower %FMD correlates with cardiovascular risk factors and subclinical atherosclerosis. 3. AB remodeling correlates with target organ damage in HTA. Different HTA phenotypes (e

1. UL RASONOGRAF DOP L R A
T
IA
PE
ART RE B
E I RAH E IN E
IAL
VAL
UARE
A
P
ACIE UL H E E
NT UI IP RT NSIV
Alexandru Andritoiu
SCUM Craiova

2. AB
•
•
•
•
Locul de masurare a TA
TA periferica vs TA centrala?
Evaluarea US – recenta
Scop de cercetare fiziologica

3. Tehnica
•
•
•
•
B-scan
Color Doppler US
Power-angio
Spectral analysis

4. Remodelarea AB
• ADAPTATIVA
 HTA
• Obezitate
• Hiper-Col
• ATS
• MALADAPTATIVA
• imbatranirea
Rol compensator!
Chung WB et al. Arterioscl Thromb Vasc Biol 2009

5. Cauze de remodelare
•
•
•
•
•
•
•
Patologice
HTA
Ateroscleroza (placi)
Hipercolesterolemie
Diabet zaharat
Obezitate
Sdr. Metabolic
Uremie-dializa
Fiziologice
• Antrenament fizic
• Imbatranirea

6. Remodelarea AB in HTA
• Proces compensator/adaptativ
• Prezervarea D/A luminale
• Shear-stress mentinut la un nivel scazut

7. Modificarile morfologice
Cresterea D si A
•
•
•
•
Mecanism adaptativ (proces compensator)
Semn de ATS
Marker de risc CV
Relatia cu ATS carotidiana, BOAP
Grosimea peretelui AB

8. Brachial artery haemodynamics
in arterial hypertension
Simon A CH, Safar ME - Br J Cl Pharmac 1984;18:243-246

9. D creste in HTA
• Normotensivi (N=25)
D = 3.2+/-0.2 mm
• HTA (N=32)
D = 4.1+/0.2 mm
p <0.001
NormoTA
D = 3.5 mm
HTA
D = 4.2 mm
Andritoiu A 2000

10. Diametrul AB - relatia cu FR-CV
Holubkov R et al. Am Heart J 143(5):802-807, 2002

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

14. Profilul anvelopei spectrale
1
3 4
2
Profilul fiziologic trifazic
,,de rezistivitate crescuta,,

15. Parametrii spectrali
•
•
•
•
•
•
•
S
D
Vmean
TAMx
IP
IR
Q (ml/min)

16. Modificari spectrale in HTA
• Largirea spectrala
• Atenuarea undei
reflectate
• Disparitia ferestrei
spectrale
• Unda tele-sistolica

17. Spectral
broadening
grading
(A) 1 p.
(B) 2 p.
(C) 3 p.
Andritoiu A, 2008
A
B
C

18. 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)

19. Modificari functionale
%FMD – tonusul vasomotor
Vasodilatatia:
• Mediata de endoteliu (Acetilcolina, metacolina)
• Independenta de endoteliu (nitroprusiat, NTG-sl)
• Mediata de flux (compresie)

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

23. Conditions Associated With Impairment in
Endothelium-dependent Vasodilation
Cardiovascular Risk Factors
• Hypercholesterolemia
• Atherosclerosis
• Type I and II diabetes mellitus and
insulin resistance
• Male sex
• Smoking
• Systemic 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
Kevin M. Sowinsk - Medscape Pharmacists 2000

25. Disfunctia endoteliala (AB)
•
•
•
•
•
Relatie cu FR-CV
Relatie cu BCI
Relatie cu ATS carotidiana
Relatie cu IxGB
Relatie cu D-AB

26. 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

27. 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

28. Probe position in relation to cuff

29. 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.

31. 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

32. 4 min
The unsolved issue is the broad spectrum
of %FMD reference value
-1.9 – 19.2
!?!
Bots ML et al. Eur Heart J 2004

34. 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. Corretti, Todd J. Anderson, Emelia J. Benjamin, David Celermajer,
Corretti
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

35. Representative flow-mediated response of
brachial artery
(forearm occlusion)
1)
2)
3)
4)
baseline diameter (DBL),
maximum diameter after cuff release (Dmax)
diameter 3 minutes after cuff release,
time of maximum diameter after cuff release.

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

37. Peak percentage change in brachial artery
diameter post-reactive hyperemia
Peak vs Total hyperemia ?
Vasoactive
substances
• Ach
• NTG
Mechanical stress
• Forearm ischemia
induced 4 min. by
an occluding cuff
Pyke KE et al. Appl Physiol 2007

38. 30 sec
60 sec
180 sec

39. Flow-Mediated Vasodilation
A Diagnostic Instrument, or
an Experimental Tool?

40. Disfunctia 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 patternul HVS
Rizzoni D 1998, Gomez C 2002, Andritoiu A 2004, Muiesan L 2004

42. Relatia %FMD –TOD in HTA
11.88
10
FMD%
7.37
NonTOD
1TOD
2TOD
6.85
3TOD
Xu J et al. J Hum Hypertens 2009

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

45. HTA – fenotipuri hemodinamice
diferite
•
•
•
•
•
HTA la tanar
HTA primara
HTA sistolica izolata
Preeclampsie
WC-HT

46. %FMD in WCH vs SEH
SEH – HT sustinuta
WCH – HT de halat alb
Gómez-Cerezo J et al. Hypertension. 2002;40:304

47. HTA la varstnici
%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

48. Variatia circadiana a %FMD in HTA
%FMD
4.37
4.28
12
21
2.22
Orele
7
Kollias GE J Hum Hypertens 2009

49. Relationship Between Carotid Artery
Intima-Media Thickness and Brachial
Artery Flow-Mediated Dilation in MiddleAged Healthy Men
R.T. Yan, T.J. Anderson, F. Charbonneau, L. Title, S.
Verma, E. Lonn, on behalf of the FATE Investigators
• Carotid 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.
Yan RT et al- JACC 2005

50. Correlation between Flow-Mediated
Vasodilatation of the Brachial Artery and
Inima-Media Thickness in the Carotid Artery
in Men
5.1+/-0.6%
• 34 M with ATS vs controls
• 61+/- 2 yr
• B-mode US
%FMD
CIMT
P<0.01
2.8+/-0.4%
%FMD
ATS
Control
%FMD showed a significant negative correlation with IMT of CCA
Hashimoto M et al. Arteriosclerosis, Thrombosis and Vascular Biology 1999

51. Relatia CIM ACC-%FMD
Yan RT et al. J Am Coll Cardiol, 2005; 45:1980-1986

53. %FMD – CIMT - PWV
135 pts
• 110 pts - CVRFs
• 33 pts. -CAD,
stroke, PAD
METHOD
o
o
o
o
US
CIMT/plaques
BA-FMD%
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
measurements will be of
stronger clinical
relevance !
Kobayashi K et al. Atherosclerosis 2004

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

55. Caz clinic
•
•
•
•
•
NE, 56y, F
Hiper-CT
HTA
Car ATS 2/6
FMD =12%
AB-largirea anvelopei spectrale

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

57. Relatia AB cu CIMT
•
•
•
•
•
•
•
Mean CIMT - CA ATS stage
Max CIMT - CA ATS stage
Mean CIMT - BA area
Max CIMT - BA area
BA area - CA ATS stage
BA TAMx - BA spectral-broad. score
BA TAV - BA spectral-broad. score
r = 0.74; p<0.001
r = 0.51; p<0.01
r = 0.40; p<0.05
r = 0.32; p<0.05
r = 0.47; p<0.01
r = 0.73; p<0.001
r = 0.66; p<0.001
Andritoiu A, 2008

58. %FMD in predictia HTA

59. •
•
•
•
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 !

60. Hiperemia reactiva (%FMD)
este predictor de PE !
12
10
11+/-4.5
• %FMD sapt 18-24
• predictor precoce
8
•
•
•
•
6
4
1.6+/-1
2
0
PE
Sb 88%
Sp 93%
VPP 84%
VPN 94.8%
Norm
Takase B et al. J Hum Hypertens 2003

61. HTA 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

62. %FMD-relatia cu varsta
Average brachial and popliteal responses to nitroglycerin (NT in young and older subjects.
G)
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

63. AB - tinta terapeutica?

64. Obiective
• Remodelarea arteriala
• Imbunatatirea functiei endoteliale
• Imbunatatirea proprietatilor peretelui
arterial

65. Antihipertensive
Efecte terapeutice
•
•
•
•
•
IECA
Sartani
Ca-antag.
Diuretice
Beta-bloc
End (++), Remod (++)
End (+/-), Remod (+/-)
End(+), Remod (++)
End (-), Remod (-)
End(+/-), Remod (-)

66. 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)
FMD%
TAS (mmHg)
Gokce, N. et al. J Am Coll Cardiol 2002;40:761-765

67. Modificarile FMD-AB dupa 6-12 luni de terapie antihipertensiva
(nifedipina) – 58 pacienti
Muiesan ML et col. Hypertension 1999;33:575-580

68. %FMD - Carvedilol
5.1% ± 0.5% at baseline to 7.8% ± 0.5%; p < .05
Matsuda Y et al. Am Heart J 140(5):753-759, 2000

70. 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

71. Studii personale
• Comportamentul vasoactiv al arterei brahiale pa
pacientii hipertensivi-studiu comparativ EcoDoppler. 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
clinical utility. Conf SRUMB, Timisoara 2009

72. MESAJE
• 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 – marke r suro g at de A !
TS
• Examinarea US a AB va fi asociata examinarii
arterelor mari (Car, Fem) !