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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