How to Measure

Arterial Function

2005.11.25

서울대학교병원

박진식

Arterial Function

• Endothelial function

• Conduit function

• Dampening function

Endothelial Function

• Vascular tone– Flow Mediated Dilatation

• Coagulation

system– Measuring soluble

markers

Conduit Function

• Ankle-Brachial Index (ABI),

Intima-Media Thickness (IMT)

• Impaired by occlusive lesions

– Atherosclerosis

– Medium sized conduit artery

– Coronary/Cerebral artery

Dampening Function

• Stiffness, Distensibility, Compliance

• Impaired by arterial stiffening

– Arteriosclerosis

– Large sized elastic artery

– Aorta/Carotid artery

Development of Arterial Dysfunction

Impaired Endothelial Function

Impaired Conduit Function

Impaired Dampening Function

How to Measure Arterial Function

• Non-Invasive Methods

Basic Principles

Clinical Implications

Comparison among the Methods

Endothelial Function

Brachial FMD

Endo-PAT

Flow Mediated Dilatation (FMD)

• Basic principles

– Endothelium dependent vasodilation

vs. endothelium independent vasodilationNeurotransmitter

Hormone

Shear Stress

Direct NO Donor

Baseline Measurement

Avascularization

Reactive Hyperemia

Shear Stress

NO release from Endothelium

Vasodilation

L-Arginine-Nitric Oxide Pathway

L-ArgeNOS

Shear Stress

Citrulline

NO

Endothelial

Cell

ROS

Agonist(Ach)

Extracellular

Space

Vascular

Lumen

ecSOD

NO

Peroxynitrite

Ca2+

sGC

GTP

cGMP Relaxation

Ca2+

Ca2+

++

+

+Smooth

Muscle

Cell

Brachial FMD

ameterBaselineDi

ameterBaselineDierPeakDiametFMD

)((%)

Healthy : 10-20%

Endo-PAT

A

C D

B

C

D

A

BPATindexRH

PAT vs. FMD-Correlation

PAT vs. FMD-Clinical Implications

Conduit Function

Ankle Brachial Index

Intima-Media Thickness

Ankle-Brachial Index

• Decreased in arterial

occlusive disease – ABI ≥ 1.0: normal

– ABI 0.8 - 1.0: mild occlusion

– ABI 0.5 - 0.8: moderate

occlusion

– ABI ≤ 0.5: severe occlusion

SBPHighestArm

AnkleSBPABI

Ankle-Brachial Index-ASx

Intima-Media Thickeness

• Carotid IMT • Brachial IMT

Dampening Function

Arterial StiffnessPulse wave velocity

Augmentation Index, Pulse pressure

SPCA, DPCA

Arterial Stiffness-Basic Principles

• Pulse wave travels faster through the stiffer artery.

proximal distalwave

reflection

soft/slow

stiff/fast

soft/slow

stiff/fast

PWV

Applanation Tomometry

• f(Peripheral wave form) ≈ Central wave form

– Generalized transfer function

Gender specific transfer function

– Estimation of

• Central BP

• Augmentation index(AIx) ( r=0.66 )

AoBA )( AoBA )(

Arterial Stiffness & CV Disease

↑ Central wave

Reflection

↑ Aortic stiffness

↑ Vascular endothelial damage

& Mechanical fatigue↑ PP

Atherosclerosis

- Stroke

- Myocardial Infarction

- Renal Failure

↑Myocardial O2 demand

↑LVH

↓Coronary perfusion

↑Myocardial O2 demand

↑LVH

↓Coronary perfusion- LVH and CHF

- Aneurysm formation

and rupture

Association of CV Risk Factors & APWV

7.14

8.38

7.67

8.7

8.03 8.11

8.59

9.72

8.89 8.89 8.72

9.389.74

8.87

5

10

Age(>60)

Male

DM

HTN

SBP>=140

Dyslip

SMK

P<0.0001 p=0.0026

p=0.0166

AP

WV

(m/s

ec)

p=0.0003

Association of APWV and CAD Severity

10.16

8.998.72

7.49

6

9

12

NL 1VD 2VD 3VD

AP

WV

(m/s

ec)

Vessel Score

Pulse wave velocity

• CV Risk factors ass with increased PWV– Increasing age / Hypercholesterolemia

– Type II diabetes / Sedentary lifestyle

• CAD and PWV in hypertensives– ↑ all cause mortality(OR = 1.34 / ↑5m/sec)

– ↑ CV mortality(OR = 1.51 / ↑5m/sec)

– ↑ mortality( PWV > 13m/sec)

• Progression of PWV– ↑ in Cr>8mg/dl

– Normotensive < Controlled HTN < HTN

• Reduction of PWV results in ↓ mortality in ESRF pt– RR of 0.71 for all cause mortality / ↓ 1m/sec PWV

Relating change in diameter (or area) of an

artery to distending pressure

• CV risk factors and Carotid Distensibility– Hypertensives vs Normotensives : CCA

• DistMAP: Hyper > Normo

• Dist100,Dist110 : Hyper = Normo

• Distending pressure alone is determinant

– Aging• ↑ age ↑Dist100

• structural change of arterial wall during aging process

– Dist using IVUS• Age, CHD, Hypertension, Hypercholesterolemia, Acutely after smoking ↓ Dist

– Dist using MRI• Age, diastolic HF ↓ Dist

• Clinical outcome and Carotid Distensibility– ↓ Dist of Carotid a. all cause mortality in ESRF pt

Systolic Pulse Contour Analysis(SPCA)

• CV risk factors and radial AIx

– AIx increased in old age, type I DM,

hypercholesterolemia

• Clinical outcome and Carotid AIx

– ↑ AIx ↓ exercise capacity in CHD pt

– ↑ AIx all-cause & CV mortality in ESRF pt

even in pt with normal PWV

(<11m/sec)

Diastolic Pulse Contour Analysis(DPCA)

• Two component of diastolic wave form

– C1(Large artery compliance) : exponential decay curve

– C2(Small artery compliance) : other component

• Marker for early vascular disease

• CV risk factors and DPCA

– ↓ C1 is ass with

• ↑ SBP

– ↓ C2 is ass with

• Type II DM, Meopaused women with CHD, Smoking

• Reliability ???

Comparison of the Different

Methodologies

Correlations

FMD,IMT,PWV

Correlations - Methods

• Subject

– 168 people (118 men, mean age ; 55YO) who received the ‘carotid ultrasound and vascular function tests’ in ‘SNUH Healthcare System’ during November, 2003 ~ June, 2005

• IMT, FMD ; GE vivid 7, 7.5-10.5MHz probe

• PWV, ABI ; FUKUDA VS-1000

IMT & PWV

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.000.0

2.5

5.0

7.5

10.0

12.5

15.0

17.5

IMT (mean) (mm)

PW

V (

m/s

)

IMT mean & PWV

(r= 0.35, p < 0.0001)

IMT max & PWV

(r= 0.34, p < 0.0001)

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.000.0

2.5

5.0

7.5

10.0

12.5

15.0

17.5

IMT (max) (mm)

PW

V (

m/s

)

IMT & FMD

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.000

5

10

15

20

25

30

35

IMT (mean) (mm)

FM

D (

%)

IMT mean & FMD

(r= -0.16, p = 0.039)

IMT max & FMD

(r= -0.15, p = 0.052)

0.00 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.000

5

10

15

20

25

30

35

IMT (max) (mm)

FM

D (

%)

PWV & FMD

PWV & FMD (r= -0.178, p = 0.02)

0 5 10 15 20 25 30 350.0

2.5

5.0

7.5

10.0

12.5

15.0

17.5

FMD (%)

PW

V (

m/s

)

Determinant of Arterial Function

• FMD (functional) ; SBP, Hb A1c, Cr

• IMT (anatomical) ; age, HTN, SBP, DM, FBS,

Hb A1c, LDL, smoking, homocysteine

• ABI (stenosis) ; SBP, Hb A1c

• PWV (mechanical nature) ; age, HTN, SBP

Different Mechanisms

Future

• New parameters to stratify CV risk

• New therapeutic target to reduce CV risk

• Before wide acceptance

– Standardization

– Consider the confounding factors