죽상경화증의 측정법

대구가톨릭의대

김기식

Why other surrogates?

Markers we have are not telling us the whole story

• 40% of patients with coronary events have normal blood pressure and cholesterol

• Sijbrands found that 40% of Dutch familial hypercholesterolaemics had a normal lifespan

• In over 25% of patients with CAD the first symptom they experience is sudden death

After Normal Process

Damage Endothelium(Injury)

Endothelial dysfunction(generalized)

Endothelial dysfunction(Regional/local modification)

Raised Lesion in Vessel wall/Atherosclerotic Plaque

Plaque Vulnerability to Rupture

Plaque Rupture

Clinical EventDeath, MI, UA

Local FactorsTime

Magnitude

Silent Progression ofPlaque Growth/Obstruction

Assessment Method

FMD

FMD IMT

FMD IMT

IMT Tissue typing

Tissue typingAngiographyIVUS

Major Vascular Manifestations of Atherothrombosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6

Transient ischemic attack

Angina:• Stable• Unstable

Ischemicstroke

Myocardial infarction

Peripheral arterial disease:• Intermittent claudication• Rest pain• Gangrene• Necrosis

측정 방법

• Biomarker

• Imaging marker

Ultrasound

X-ray: EBCT, MDCT

MRI

Imaging Marker

Carotid Artery Ultrasound

• Carotid IMT

• Carotid plaque

경동맥의 초음파 해부학

• Internal carotid artery: posterior & lateral to external carotid artery, low resistance

• ECA: branching, Doppler spectral change with temporal a. tapping

• CCA bifurcation: normal flow separation

• Vertebral artery: arise from superior orposterosuperior wall of subclavian a.

검사 방법• Neck extension with face toward

to contralateral side

• 5-10 MHz transducer– Transverse and longitudinal scan

– Plaque: echo, shape, surface, thickness

– Diameter reduction and area reduction (transverse & longi scan)

Anterior neck approachPosterior neck approach

Short Axis View

CCAICA

ECALong Axis View

PlaqueAbnormal

thickeningNormal

ICA

ECA

Morphology • Wall thickness

– Risk factor for coronary artery disease

– Risk factor for cerebrovascular disease

– Risk factor for peripheral artery disease

• plaque– Existence and quantity

– Echogenecity

– Plaque ulceration

– Carotid stenosis

Characterization of Carotid Atheromatous Plaque

• Fibrofatty, fibrocalcific, calcific type

• echogenecity: 균일한 것과 비균일한 것

•비균일한 죽상 경화반: 석회화, 콜레스테롤침착, 출혈

• Plaque cap rupture: irregular surface

– thrombosis, peripheral embolization 유발

Table. Hazard ratio of mortality risk in relation to carotid plaques adjusted for age

Circulation 2004;110:314

Media

Adventitia

Intima

10 mm10 mm10 mm

CCA Bulb Bif CA

IMT

Diagram of measurement of Intima-Media Thickness( IMT) by 10 MHz Transducer

Carotid IMT (cIMT) Testing

• Noninvasive, safe, inexpensive, accepted by patients, ethically sound

• Identifies minor (early) and major (late) ASO

• Nomograms (age, sex, and race-based) for normal values exist

• Predicts risk of future MI and STROKE

• Incremental predictive power

• Recommended by AHA for patients > 45 for “further clarification of CHD risk”

In one population-based study cIMT was the single risk factor best able to predict cardiovascular events, with a level of event

prediction nearly as great as all of the other risk factors combined !!!

del Sol AL, et al. Stroke 2001, 32:1532

IMT of the CCA : Associated Factors

• Hypertension

• S-Cholesterol levels

• Smoking

• Diabetes (time of disease)

• Lower socioeconomic status

Which is the better site for IMT Measurement between CCA or ICA

• Common carotid artery is easier to image and lesser variable than the ICA because of angle of beam or depth of the vessel ( CHS study)

ie; Success rate for faired far wall measurment

89% (109/122) in CCA

38% (140/366) in ICA ( Rotterdam study)

• Both is better because focal atherosclerotic lesions are much more prevalent in the ICA than in the CCA

717383N =

55~6445~5435~44

.8

.7

.6

.5

Normal Profiles (Korean)

95% CI of right IMTcca

Age (yrs)

0.58±0.09

0.63±0.11

0.70±0.11

p=0.02

p<0.001

p=0.001

717382N =

55~6445~5435~44

.8

.7

.6

.5

95% CI of left IMTcca

0.59±0.08

0.64±0.11

0.70±0.11p=0.005

p<0.001

p=0.001

Total n=227 Total n=226

Common CIMT and Risk of First Stroke and MI(Rotterdam Study, 1997)

First Stroke New MI

<0.75 0.75 0.83 >0.92 <0.75 0.75 0.83 >0.920.82 0.91 CCIMT (mm) 0.82 0.91

Odds ratio

1.34 vs 1.25

IMT MI and Stroke: CVHS

9.2

8.6

7.8

18.4

13.7

13.6

16

21.4

18.4

23.8

22.3

22.2

36.5

36.1

40.9

0

5

10

15

20

25

30

35

40

45

MI

or

Str

ok

e R

ate

/1

00

0p

-

yea

r

1 2(1.54) 3(1.84) 4(2.01) 5(3.15)

Quintiles d'EIM (ORA)

MI and Stroke Incidence according to the IMT quintile

CCA ICA CCA ICA

DH O ’Leary et coll NEJM Jan 99

The Relationship between Intima-media thickness(IMT) of Carotid artery and the plaque

burden of Left main coronary artery(LM)

To evaluate the relationship between the IMT of CCA and plaque burden of Left mainCoronary artery.

Result

52/M, Angina, smoker

61/F, Angina, nonsmoker

Max 0.827mm

Mean 0.620mmMax 0.904mm

Mean 0.666mm

Max 1.114mm

Mean 0.848mm

Max 1.166mm

Mean 0.930mm

Max 1.9mm

Plaque area 12.2mm2

% of plaque area 59%

Max 2.5mm

Plaque area 16.6mm2

% of plaque area 71%

Max 0.9mm

Plaque area 9.4mm2

% of plaque area 38%

Max 1.1mm

Plaque area 11.6mm2

% of plaque area 41%

Max 1.3mm

Plaque area 12mm2

% of plaque area 33%

Max 1.1mm

Plaque area 10mm2

% of plaque area 31%

Max thickness 1.3mm

Plaque area 11mm2

% of plaque area 32%

Max thickness 2.5mm

Plaque area 12.5mm2

% of plaque area 52%

Right

Right

Left

Left

Result

Correlation between max IMT and LM plaque

maximal IMT(mm)

% of LMPlaquearea

10

20

30

40

50

60

70

.5 .6 .7 .8 .9 1 1.1 1.2 1.3 1.4

r=0.41

p=0.003

Interventional StudiesLipid Lowering

STUDY AGENT TIME IMT

MIDAS colestipol/niacin 3 years progression

KAPS/CAIUS Prava vs pbo 3 years progression

REGRESS Prava vs pbo 3 years progression

ACAPS Lova vs pbo 3 years progression

ASAP Atorva 80 vs 2 years regressionSimva 40

Interventional StudiesAnti-hypertensives

STUDY AGENT TIME IMT

VHAS verapimil vs chlothal 3 years progression

PREVENT amlodipine vs usual care 3 years progression

SECURE ramipril vs pbo 4.5 years progression

ARES amlodipine vs enalapril 2 years regression

Multislice CT for Detection of Atherosclerosis

MDCT의 유용성

• 관동맥의 해부학적 구조

• 관동맥의 협착 정도와 위치를 파악한다

• 중재시술후 추적 검사로 사용이 가능하다?

• CABG를 시행한 환자의 추적 검사

• 죽상경화증의 성상과 양을 알 수 있다

LAD calcification

Diagnostic Accuracy ofNoninvasive Coronary

AngiographyUsing 64-Slice Spiral CT

Raff GL et al. J Am Coll Cardiol 2005;46:552–7

64-MDCT의 정확도Author Journal Sen Spe PPV NPV

Mollet NR Cir 05„ 99% 95% 76% 99%

Leschka S EHJ 05 „ 94% 97% 87% 99%

Pugliese F E Rad 05' 99% 96% 78% 99%

100% 90% 96% 100%

Raff GL JACC 05' 86% 95% 66% 98%

91% 92% 80% 97%

95% 90% 93% 93%

64-Slice MDCT

(+ high HR, < D:1.5 mm)

(S)

(P)

(S)

(A)

(P)

CT plaque characterization

• Tissue Density HU

– Bone - 1000

– Water - 0

– Lipid - 50

– Air - 1000

Type

ThrombosisAtheromaFibroticcalcific

In-vivo*

205060

>130

Ex-vivo**

-47104-

* Becker C et al. AHA 2001**Giesler T. et al. RSNA 2001

Coronary calcification

None Mild Severe

Soft Plaque

Non-enhance enhance

“Triple Rule Out (CAD, PAT, AD)”

Intramural Hematoma with Overt Aortic Dissection

M/41, Acute chest painECG: LBBB, V1~V4 ST elevationR/O STEMI, Aortic dissection, Pulmonary Embolism

Major Limitation

Nieman et al. Lancet 2001

결론

• 초음파도, MDCT등 영상 장비를 이용한 직접적인 죽상경화증의 진단은 다른 위험인자에 비해 강력한 예측능을 보여 심근경색증, 뇌졸중의 예방에 많은 도움이 될수 있다.

• 이러한 영상 진단은 임상에서 쉽게 시행이 가능하며환자에 교육적인 측면도 강해 치료의 순응도를 높일수 있다.

• 앞으로 기술적인 발전은 급속히 진행될 것으로 보이며이러한 이유로 관혈적 진단 방법을 상당 부분 대치할것으로 예측된다