96091164 Slice Ct And Cerebral Atherosclerosis02

Analysis of cerebral atherosclerosis and risk factors of stroke using 64-slice

computed tomography6464 排電腦斷層應用在頸動脈血管硬化和排電腦斷層應用在頸動脈血管硬化和

腦中風危險因子之分析腦中風危險因子之分析

Cerebral aneurysmCerebral aneurysm

Saccular (Berry) Aneurysm

Saccular aneurysms occur at the bifurcations of the large to median-sized intracranial arteries.

The risk of rupture of an aneurysm <7 mm in diameter is 0.05% per year, far less than the 5% to 10% risk of major complications with intervention, either by coiling or clipping.

Incidentally discovered small aneurysms should be re-evaluated periodically for enlargement.

Treatment with aspirin does not increase the risk of aneurysmal rupture. Aspirin may be associated with more bleeding if the aneurysm ruptures spontaneously, but may reduce complications such as vasospasm.

Carotid atherosclerosisCarotid atherosclerosis

Albers, G. W. et al. Chest 2004;126:483S-512S

The most frequent sites of arterial and cardiac abnormalities causing ischemic stroke

Atherosclerosis • 動脈硬化斑塊可分為兩種 : 一種為穩定的動脈硬化斑塊一種為不穩定的動脈硬化斑塊。泡沫細胞所分泌的發炎物質會分解基質而造成纖維外膜的

脆弱，並藉由破壞平滑肌細胞而使得外膜無法修補。當不穩定的動脈硬化斑塊產生裂縫時，內皮細胞會暴露出下層的細胞外基質，暴露的細胞外基質和血小板受體結合之後會造成血小板的活化 (activation) ，導致醣蛋白 IIb-IIIa 暴露出和纖維蛋白原結合的部位，使得纖維蛋白原將血小板拉在一起而造成血小板的凝集 (aggregation) 。

血栓表面會有促進凝血的作用，如果再加上動脈斑表現出組織因子 (tissue factor) ，會使凝血路徑啟動進而導致thrombin 的生成。

Thrombin 對於血小板是一個強力的引發劑 (inducer) ，造成血小板內部 ADP (adenosine diphosphate) 及TXA2 (thromboxane A2) 的釋放因而導致更多的血小板活化及附著至血栓處，使得血栓擴大而引起血管阻塞。

AHA Classification of Atherosclerotic Plaque

(Circulation. 2002;106:1368.)

Type I: initial lesion with foam cells Type I–II: near-normal wall thickness, no calcificationType II: fatty streak with multiple foam

cell layers

Type III: preatheroma with extracellular lipid pools

Type III: diffuse intimal thickening or small eccentric plaque with no calcification

Type IV: atheroma with a confluent extracellular lipid core

Type IV–V: plaque with a lipid or necrotic core surrounded by fibrous tissue with possible calcificationType V: fibroatheroma

Type VI: complex plaque with possible surface defect, hemorrhage, or thrombus

Type VI: complex plaque with possible surface defect, hemorrhage, or thrombus

Type VII: calcified plaque Type VII: calcified plaque

Type VIII: fibrotic plaque without lipid core

Type VIII: fibrotic plaque without lipid core and with possible small calcifications

Classification of Human Carotid Atherosclerotic Lesions With In

Vivo Multicontrast Magnetic Resonance Imaging (Circulation. 2002;106:1368.)

• Sixty patients (mean age 70 years; 54 males) scheduled for carotid endarterectomy were imaged with 4 different contrast-weighted MRI (time of flight and T1-, PD-, and T2-weighted) of the carotid arteries.

• Carotid plaques were removed intact and processed for histological examination.

• The sensitivity and specificity, respectively, of MRI classification were as follows: type I-II lesions, 67% and 100%; type III lesions, 81% and 98%; type IV-V lesions, 84% and 90%; type VI lesions, 82% and 91%; type VII lesions, 80% and 94%; and type VIII lesions, 56% and 100%.

• Conclusions—high-resolution multicontrast MRI is capable of classifying intermediate to advanced atherosclerotic lesions in the human carotid artery and is also capable of distinguishing advanced lesions from early and intermediate atherosclerotic plaque.

Type IV-V

Type VI

Duplex ultrasonography plus magnetic resonance angiography

• 8% false-positive rate for Doppler (not duplex) evaluation. false-negative rate could not be evaluated • Magnetic resonance angiography tends to overestimate the

degree of stenosis. (J Neurol Neurosurg Psychiatry. 1994; 57:1466-78)

• Transcranial Doppler ultrasound and magnetic resonance angiography identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The methods reliably exclude the presence of intracranial stenosis. Abnormal findings require a confirmatory test such as angiography to reliably identify stenosis. (The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial SONIA)

64-slice CT• 64 排電腦斷層掃描儀，對於冠狀動脈狹窄

的偵測已有 85 至 99 ％的敏感度，特異性達 95 至 98 ％，因而對於冠心病的正確診斷，並不亞於傳統侵入性的心導管檢查

64-slice CT demonstrated a sensitivity of 93%, specificity of 96%, and positive and negative predictive values of 78% and 98%, respectively, for detecting significant coronary stenosis on a segment-by-segment basis (Society of North America 92nd Scientific Assembly and Annual Meeting; November 26-December 1, 2006; Chicago, Illinois. Page 209)

Plaques thickness

ulcerated plaques

Plaques with mobile components

鈣化指數計量 (CACS)

鈣化指數計量與冠心病• CS= 0 代表沒有鈣化的粥樣硬化斑塊，這意味著並沒有有意義的冠狀動脈狹窄而且至少未來 3 年會有冠心病的可能性非常低。但這並不能絕對地排除或減少可能因軟性的、非鈣化的粥樣硬化斑塊所造成的冠心病機率。

鈣化指數 (1,2)

涵義冠心病的危險度

0 無法偵測到斑塊非常低，通常低於 5%

1 - 10 可偵測到微細斑塊不見得會有，低於 10%

11 - 100很確定 , 至少有輕度粥樣硬化

斑塊可能會有輕度或微量冠狀動脈狹窄

101 - 400很確定 , 至少有中度粥樣硬化

斑塊非常可能有輕度冠狀動脈狹窄，可能會有

有意義的狹窄

401 or Higher

廣泛性粥樣硬化斑塊會有至少一條冠狀動脈有意義狹窄的高度可能

鈣化指數計量與冠心病

Mayo Clinic Proceedings, 1999 Carr JJ, et. Al, AJR 2000

冠狀動脈鈣化（ CAC）指數與冠狀動脈電腦斷層血管攝影術診斷率如何？

1. CAC診斷冠心病的診斷率其敏感性為 81％～ 88％，專一性為 52％～ 61％，如果指數為 0 時，不具有冠心病的準確度也可達 92％。

2. 冠狀動脈 CTA的診斷率如以大於 2mm的管徑言，其血管阻塞率達 50％以上之診斷敏感性為 95％，專一性為 86％。

Composition of the stable carotid plaque Insights from a multidetector computed tomography study of the plaque volumn

• The proportion of carotid plaque calcification, rather than absolute volume, is associated with stability in patients with stenosis.

• Plaque calcification 45% of the total volume may represent a clinically useful cutoff.

• The carotid plaque calcium ratio, determined by multidetector computed tomography volume measurements, may help noninvasively risk stratify patients with asymptomatic stenosis.

(Stroke. 2007;38:935-940.)

EVIDENCE-BASED EVIDENCE-BASED MEDICINEMEDICINE

A stroke patient with moderate (50-69%) carotid stenosis

A 65 year old man with a stroke. He has mild weakness of the right arm and right leg. We send the patient for CT angiogram and receive the report that he has moderate stenosis (50-69% by NASCET criteria---the narrowest protion of the vascular lumen

compared with the normalized lumen distally) of the ipsilateral carotid artery.

How effective is a carotid endarterectomy in someone

with moderate carotid stenosis?

Step IPatient or Problem

Step IIIntervention

Step IIIComparison Intervention

Step IVOutcome

Description of the patient or the target disorder of interest

Could include: · Exposure · Diagnostic test · Prognostic factor · Therapy · Patient perception etc.

Relevant most often when looking at therapy questions

Clinical outcome of interest to you and your patient

Patient or Problem Intervention Comparison Intervention

Outcome

65 year old man with stroke and moderate carotid stenosis

Carotid endarterectomy

Medical therapy Stroke or outcome of death

In a 65 year old man with stroke and moderate carotid stenosis, can carotid endarterectomy decrease the risk of stroke or outcome of death compared with medical therapy?

Endarterectomy in patients with symptomatic carotid stenosis

~13% per year stroke rate• Patients with stenosis of less than 50 percent

did not benefit from surgery. • patients with symptomatic moderate carotid

stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke.

• Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

NASCET (the North American Symptomatic Carotid Endarterectomy Trial) and ECST (the European Carotid Surgery Trial) N Engl J Med. 1998 Nov 12;339(20):1415-25

• In Patient s with a stenosis > 70%, the stroke risk at 2 years was

26% for patient treated medically 9% for the same medical treatment

plus a carotid enderectomy

• This 17% absolute reduction in the surgical group is a 65% relative risk reduction favoring surgery

• Harm for patients with stenosis in the 0 to 30% treated surgically

Endarterectomy in patients with asymptomatic carotid stenosis≥60%

~2% per year stroke rate

• The surgical group had a risk over 5 years for ipsilateral stroke is 5.1%, compared to a risk in the aspirin group of 11% (half of the stroke in the surgical group were caused by preoperative angiogram)

• 53% relative risk reduction and 5.9% absolute risk reduction over 5 years and 1.2% annually

ACAS (Asymptomatic Carotid Atherosclerosis Study) andACST (Asymptomatic Carotid Surgery Trial)

Endarterectomy in patients with asymptomatic carotid stenosis≥60%

• Carotid endarterectomy is controversial

• Medical therapy for reduction of atherosclerosis risk factors, including cholestrol-lowering agents and antiplatelet medications is recommended

Relative Number needed to

Risk Production Treat

Relative with Primary Secondary

Risk factor Risk Treatment Prevention PreventionHypertension

Atrial fibrillation

Diabetes

Smoking

Hyperlipidemia

Asymptomatic carotid stenosis

Symptomatic carotid stenosis (70-99%)


2-5

1.8-2.9

1.8-6

1.8

1.8-2.6

2.0

38%

68% warfarin

21% aspirin

No proven effect

50%at 1 year, baseline risk at 5 years post cessation

10-29%

46-53%

65% at 2 years

29% at 5 years

100-300

20-83

85

N/A

N/A

50-100

13

N/A

12

77

健保局給付頸動脈支架使用規範使用規範如下：

　（一）無症狀的頸動脈狹窄大於 80% 以上。　（二）有症狀的頸動脈狹窄大於 60% 以上。　（三）放射線治療後之頭頸部動脈狹窄（含頸動脈、椎動脈及鎖骨下動脈）。　（四）頸動脈或椎動脈剝離所引起之狹窄或剝離性動脈瘤。　（五）因嚴重心肺疾病，不適合外科頸動脈內膜剝離術或全身麻醉者。

實施醫師之資格：　　限由心臟內科專科醫師或放射科專科醫師或神經放射科專科醫師施行，且必須具頭頸部血管攝影 30 例以上操作經驗，另有 3 例頸頸動脈支架之操作經驗，並取得由專業醫學會舉辦之置放頸動脈支架之技術訓練研討會訓練證書者。

• 　

Statins and Atheroma

Primary end point: Percent change in total plaque

volume as measured by IVUS

Primary end point: Percent change in total plaque

volume as measured by IVUS

REVERSAL — The Reversing Atherosclerosis with Aggressive Lipid Lowering Study

18-month follow-up with IVUS

502 patients

Patient population:Patient population: History of CHD History of CHD Angiographic criteria:Angiographic criteria:

− ≥≥20% reduction in 20% reduction in lumen diameter in lumen diameter in ≥≥1 coronary artery1 coronary artery

− >50% reduction in >50% reduction in lumen diameter of the lumen diameter of the left main coronary left main coronary artery artery

− ≥≥1 coronary artery 1 coronary artery with with ≤≤50% stenosis50% stenosis

Double-blind period

Atorvastatin 80 mg/day (n=253)Atorvastatin 80 mg/day (n=253)

Pravastatin 40 mg/day (n=249)Pravastatin 40 mg/day (n=249)

Study DesignStudy Design

JAMA. 2004;291:1071-1080

REVERSAL: Method For MeasurementOf Intravascular Ultrasound Images

Nissen et al. Am J Cardiol. 2005;96(suppl):61F

2.7*

Pravastatin

Significant atheroscleroticprogression from baseline

-0.4†

Atorvastatin

No significant change frombaseline; atheroscleroticprogression was stopped

Primary end point: Percent change in total atheroma volume

Cha

nge

in T

AV

(%

)

-1

0

1

2

3

*Progression vs baseline (P=0.001); †No change vs baseline (P=0.98)

P=0.02

REVERSALThe Need for Intensive LDL-C Lowering:Relationship Between Degree of LDL-C Reduction and Change in Atheroma Volume

The solid blue line indicates the relationship between mean change in LDL-C and change in atheroma volume from linear regression analysis. The dashed green lines indicate the upper and lower 95% confidence limits for the mean values. Nissen S et al JAMA 2004;291:1071–1080.

% Change in LDL-C

Ch

ang

e in

ath

ero

ma

volu

me

(mm

3 )

–15

–10

–5

0

5

10

15

20

–80 –70 –60 –50 –40 –30 –20 –10 0 10 20

N=502

Please consult local Prescribing Information for guidance on the use of CRESTOR

-1

-0.5

0

0.5

1

1.5

2

50 60 70 80 90 100 110 120

ASTEROID3 rosuvastatin

A-Plus2 placebo

ACTIVATE1 placebo

CAMELOT4 placebo

REVERSAL5 pravastatin

REVERSAL5 atorvastatin

Mean LDL-C (mg/dL)

The relationship between mean LDL-C and change in percent atheroma volume (PAV) in IVUS studies†

Change

in Percent

AtheromaVolume*

(%)

†ASTEROID and REVERSAL investigated active statin treatment; A-PLUS, ACTIVATE AND CAMELOT investigated non-statin therapies but included placebo arms who received background statin therapy (62%, 80% and 84% respectively).

*Median change in PAV from ASTEROID and REVERSAL; LS mean change in PAV from A-PLUS, ACTIVATE AND CAMELOT

1 Nissen S et al. N Engl J Med 2006;354:1253-1263. 2 Tardif J et al. Circulation 2004;110:3372-3377. 3 Nissen S et al. JAMA 2006;295 (13):1556-1565 4 Nissen S et al. JAMA 2004;292: 2217–2225. 5 Nissen S et al. JAMA 2004; 291:1071–1080

Progression

Regression

• Retrospective study of 519 patients with severe thoracic aortic plaque> 4 mm found that statins (OR, 0.39; 95% CI, 0.24 to 0.62; p = 0.0001), but not oral

anticoagulation (OR, 1.18; 95% CI, 0.91 to 1.54; p = 0.21) or antiplatelet therapy (OR, 0.77; 95% CI, 0.51 to 1.15; p = 0.20) had a significant protective effect against recurrent embolism.

Am J Cardiol. 2002 Dec 15;90(12):1333-5

Cardiovascular Disease Cardiovascular Disease (CAD)(CAD) Versus Versus

Cerebrovascular Disease Cerebrovascular Disease (CAD)(CAD)







動脈硬化的基因與蛋白質

SMC FC

A B

C D

Early stage

Late stage

Hp expression in human aorta with atherosclerosis

Macrophage cells

Hp protein

Relative Number needed to

Risk Production Treat

Relative with Primary Secondary

Risk factor Risk Treatment Prevention PreventionHypertension

Atrial fibrillation

Diabetes

Smoking

Hyperlipidemia

Asymptomatic carotid stenosis



2-5

1.8-2.9

1.8-6

1.8

1.8-2.6

2.0

38%

68% warfarin

21% aspirin

No proven effect

50%at 1 year, baseline risk at 5 years post cessation

10-29%

46-53%

65% at 2 years

29% at 5 years

100-300

20-83

85

N/A

N/A

50-100

13

N/A

12

77

Technology

96091164 Slice Ct And Cerebral Atherosclerosis02