동맥경직도 평가방법 및 임상적 의의

인제의대 부산백병원

김 동 수

Multiple Cycle of Pulsatile Stretch

Elastin Fiber Fracture

Aortic Dilatation and Stiffening

Arterial Damage

(arteriosclerosis)

(atherosclerosis)

(aneurysm formation)

Increased

Pulse Pressure

Increased Pulsatile Stress and Strain

Arterial stiffness, pulse pressure and arterial damage

Arterial Stiffness

Three processes to increase arterial stiffness

– Structural breakdown of elastin fibers

• occurs primarily in the aorta

• age driven (cum. millions of cardiac cycles)

– Damage to endothelial function

• occurs primarily in the smooth muscle conduit

arteries

• disease driven (e.g., Type II diabetes,

hypercholesterolemia, atherosclerosis)

– Increase in mean arterial pressure

• occurs systemically throughout the arterial system.

Mechanism of Arterial Stiffness

↑ Vascular stiffness / Distensibility

↑ Systolic blood pressure & Pulse pressures

↑ Atherosclerosis

IMT

Intimal migration/proliferation of VSMC

Vascular change

Collagen

Elastin

Endothelial

Dysfunction

Vascular anatomical changeArterial wall thickness (IMT)

Intimal migration/proliferation of VSMC

Subendothelial collagen

Collagen cross-linking

Elastin / Elastin fragmentation

Proteoglycans

Endothelial dysfunction Endothelial permeability

Endothelial nitric oxide , endothelin

Inflammatory markers/mediators

SOD activity

Medial wall

stiffness

CompliantSystole Diastole

Non-CompliantSystole Diastole

Constant Stroke Volume

Aorta

Pulse

pressure

Systolic BP

Diastolic BP

Arterial Wall Compliance and Pulse Pressure Wave

Curr Opin Cardiol 2004;19:341

Noninvasive Methodologies for the

Assessment of Arterial Stiffness

• Measuring Pulse Wave Velocity:

현재많이이용

• Relating change in diameter(or area) of an

artery to distending pressure

• Assessing arterial pressure waveforms:

Augmentation Index(AI), Central Aortic

Pressure, Pulse Pressure

• Known distance apart (d)

• Transit time (Δt)

Pulse Wave Velocity

* *a b

distance

A

B

A

B

t

The speed with which the pulse wave travels along a length

of artery (distance/t)

PWV = d/ Δt

Carotid art.

Femoral art.

distance

t

Noninvasive measurement of PWV

Aortic PWV

= distance (carotid-femoral art.) / t

Carotid-femoral PWV is considered as the ‘gold-standard’

measurement of arterial stiffness

Relating change in diameter(or area) of

an artery to distending pressure

• 초음파를사용하는방법으로 Carotid artery 에서 수축기와 확장기의직경을측정하고혈압과의관계 변화를계산하여평가한다.

• 혈압은일반적으로 Brachial artery에서 측정한혈압을사용한다.

• Brachial artery PP가 Carotid artery PP반영하지못해정확한 Carotid artery stiffness를 측정하기어렵다.

• Cine MRI를 이용하여근위부대동맥에서도일부 측정한다.

• 평가지표: Distensibility, Compliance, Young’s Elastic modulus, beta stiffness index

Brachial PPCentral PP

Laurent S, et al. Eur Heart J 2006 27:2588-2605

Local arterial stiffness

Parameter Definition Formula

Distensibility The relative change in vessel diameter (or

area) for a given change in pressureD/(PxD),

A/(PxA)

Compliance The absolute change in vessel diameter (or

area) for a given change in pressureD/P, A/P

Elastic modulus The pressure change required for

(theoretical) 100% stretch from resting

diameter (inverse of distensibility)

(PxD)/D

Stiffness index (ß ) The ratio of the natural logarithm of

SBP/DBP to the relative change in diameter

ln(Ps/Pd)

/ [(Ds-Dd)/Dd)]

Young’s modulus

(incremental elastic

modulus)

Elastic modulus per unit area (accounts for

wall thickness)(PxD)/(Dxh)

Definitions of some parameters commonly measured in

the assessment of local arterial stiffness

동맥의 압력맥파 (pressure wave)

진행파 (전향파형)

Forward wave

반사파 (반향파형)

Reflected wave

Observed wave

SBP

incisura

forward

reflected

건강한혈관경직된혈관

incisura

forward

reflected

Reflection site Reflection site

augmentation

Arterial stiffening

Pulse Wave Analysis

• Central pulse pressure

• Central aortic pressure

• Augmentation index (AIx)

경동맥또는요골동맥에서맥파를기록하여파형을분석

Radial artery

Pulse wave analysis (PWA) :

augmentation index (systemic art. stiffness)

Aorta

transfer function(Degree of amplification)

Radial pulse

Augmentation index

Sensor

Bone

Artery

applanation tonometry

Device to estimate pulse wave analysis

SphygmoCor

GAON (한별메디텍)

• Central pressure

• Pulse pressure(PP)(SBP-DBP)

= (P1-P3) + (P2-P1)

• AI = (P2-P1)/(SBP-DBP)

* PP = Pulse pressure

* AI = Augmentation index

* P2 = 최대수축기혈압

* P1= 반향파가돌아와서굴곡을만드는

최대지점

* P3 = 최소이완기혈압

* Δtp= 상행대동맥에서주요반향지점

까지파형이이동하는데걸리는시간

* Δtr = 반향파의수축기

Aortic pressure waveform

P1

SBP

DBP

incisura

ejection duration

PP

P2

P3

Δtp Δtr

Augmentation pressure★

parameter Main features and

definition

Limitations Technical

expertise

Carotid-

femoral PWV

Gold standard for arterial

stiffness

Speed of travel of the pulse

along an arterial segment

(L/t in m/s)

Pressure-dependent

No data on arterial geometry

Inaccuracy of distance

measurement

+

Central pulse-

wave analysis

(carotid and

aortic pressure

waves)

Central pulse pressure (PP)

Central SBP

Central augmentation

pressure (AP)

Central AIx with AIx = AP/PP

Indirect information on

arterial stiffness

+

Local arterial

stiffness

Carotid distensibility

Carotid compliance

Carotid Young’s modulus

Takes into account BP level

Requires echotracking

systems

Requires local PP

+++

Methods for measuring arterial stiffness in clinical investigation

PP

Increased CentralPulse Pressure

Increased LV Load

Decreased Coronary ArteryPerfusion Pressure in Diastole

Stiffened artery and clinical implication

Aortic arterial wave

Stroke

CHD

LVH

DiastoleSystole

Arterial Stiffness & CV Disease

↑ Central wave

Reflection

↑ Aortic stiffness

↑ Vascular endothelial damage

& Mechanical fatigue↑ PP

Atherosclerosis

- Stroke

- Myocardial Infarction

- Renal Failure

- LVH and CHF

- Myocardial stiffening

- Aneurysm formation

and rupture

↑Myocardial O2 demand

↓Coronary perfusion

Clinical conditions associated with increased

arterial stiffness and/or wave reflections

Laurent S, et al. Eur Heart J 2006 27:2588-2605

Multivariate analyses: the major parameters to be

taken into account, when evaluating the degree of

arterial stiffness, are age and BP and, to a lower

extent, gender and classical CV risk factors.

*Men aged 35-57 years followed for a mean of 12 years.

Neaton et al. Arch Intern Med. 1992;152:56-64.

<120120-139

140-159

160+

CHD Death Rate per

10,000 Person-Years

100+

80-89

70-74<70

75-79

90-99

Effect of SBP and DBP on CHD Mortality

48.3

37.4

43.8

38.1

80.631.0

25.5

25.325.2

24.9

23.8

16.9

13.9

12.8

12.6

11.8

20.6

10.311.8

8.8

8.5

9.2

Systolic BP

(mm Hg)

Diastolic BP

(mm Hg)

맥압과 심혈관 질환의 사망률

MRFIT Screenees (N=316,099)*

Clinical application

• Carotid-femoral PWV has the largest amount of epidemiological evidence for its predictive value for CV events.

• Central pulse pressure and the AIx have demonstrated their predictive value in patients with ESRD, in hypertensives, and in CAD patients.

• Local arterial stiffness benefits from a certain amount of epidemiological evidence for its predictive value for CV events.

REASON study:

PWV and augmentation index(AI)

Asmar R et al. Hypertens. 2001;38:922-926.

Aorta-AI (%)

Perindopril

+indapamide

Atenolol

P=0.112

P<0.001

-4

-3

-2

-1

0

1

2

-3.1

+1.8

PWV (ms)

P=0.002

-1.5

-1

-0.5

0

-0.79

-0.99

Perindopril

+indapamide

(n=204)

Atenolol

(n=202)

P<0.001 P<0.001

ns

With no difference of PWV Favorable with ACEi+diuretic of AI

CAFE: Lower central aortic BP with newer

vs older antihypertensive regimen

despite similar brachial BP

Amlodipine ± perindopril

Atenolol ± bendroflumethiazide

140

135

130

125

120

115

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6

Time (years)

mm Hg

Brachial SBP

Central aortic SBP

CAFE Investigators. Circulation. 2006;113:1213-25.

두 군의 약물치료에 의해 나타난 중심대동맥 혈압의 차이

CAFE: Lower augmentation index with

newer antihypertensive regimen

31.9

25.3

0

5

10

15

20

25

30

35

Augmentation

index

(%)

P < 0.0001

Amlodipine ± perindopril†Atenolol ± bendroflumethiazide*

CAFE Investigators. Circulation. 2006;113:1213-25.*Older antihypertensive regimen†Newer antihypertensive regimen

With no difference of PWV

Non-Pharmacological and pharmacological treatment associated

with a reduction in arterial stiffness: Interventional studies

Sildenafil

• Hypertension

- Re-stratification of patient risk

- Re-classification of marginal hypertension

- Optimisation of drug therapy

- Identification of spurious isolated systolic hypertension

• Cardiac failure

- Distinguish systolic vs diastolic dysfunction

- Determine severity of systolic dysfunction

- Precise measure of LV load

- Index of subendocardial viability

• Diabetes

- Early identification of cardiovascular risk

• Baro-receptor function

• Ischaemic heart disease

- Optimise medical therapy

- Identify patients with short end diastole

Clinical application of pulse wave analysis

동맥경직도 평가의 임상적 의의

• 심혈관계 질환의 표지자 뿐 만 아니라 치료에 대한예후를 예측

• 여러 약제의 동맥경화에 대한 치료효과를 평가

• 여러 질환에서 동맥경화가 발생하는 병태생리를연구하는 데 사용

A number of technologies can measure arterial stiffness noninvasively. The relatively low cost, ease of use, and acceptability to patients of many of these technologies has resulted in a rapid expansion of work in this field, although the full clinical impact of these measurements is not yet clear.