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Carotid Plaque & IMT Carotid Plaque & IMT

Imaging: Where Do We Imaging: Where Do We

Stand?Stand?

Roger S. Blumenthal, MD, FACCRoger S. Blumenthal, MD, FACC

Professor of MedicineProfessor of Medicine

Director, Johns Hopkins Ciccarone Center Director, Johns Hopkins Ciccarone Center for the Prevention of Heart Diseasefor the Prevention of Heart Disease

Disclosures: NoneDisclosures: None

ObjectivesObjectives

�� Limits to FRS predictionLimits to FRS prediction

�� Carotid ultrasound as tool to predict Carotid ultrasound as tool to predict

cardiovascular disease riskcardiovascular disease risk

�� Carotid plaque presenceCarotid plaque presence

�� Carotid intimaCarotid intima--media thickness (CIMT) media thickness (CIMT)

measurementmeasurement

�� Consensus statement from ASE/SVMConsensus statement from ASE/SVM

Limitations of Current CV Risk Limitations of Current CV Risk

Prediction ModelsPrediction Models

�� Heavily dependent on ageHeavily dependent on age

�� Do not account on changes in patient’s health Do not account on changes in patient’s health status over timestatus over time

�� Focused on shortFocused on short--term (10term (10--year) riskyear) risk

�� Family history not incorporated into estimatesFamily history not incorporated into estimates

�� Patients with high levels of a single risk factor Patients with high levels of a single risk factor may not be correctly classified solely on FRSmay not be correctly classified solely on FRS

�� Smoking considered as present or absent onlySmoking considered as present or absent only

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Advantages of Carotid Ultrasound as Advantages of Carotid Ultrasound as

an Imaging Modalityan Imaging Modality

�� NonNon--invasive, safeinvasive, safe

�� InexpensiveInexpensive

�� Readily available, Readily available, portable, and quickportable, and quick

�� Plaque visualizationPlaque visualization

�� HemodynamicsHemodynamics

�� OfficeOffice--based assessmentbased assessment

Ultrasound Ultrasound Assessment of Assessment of

Carotid Carotid IMT and Plaque PresenceIMT and Plaque Presence

mediamedia

adventitia

intimaplaque

Advantages of Carotid Advantages of Carotid Study To Study To

Refine Refine Risk Prediction Risk Prediction �� Completely noninvasive Completely noninvasive –– no radiation, no harmful no radiation, no harmful

exposures, no known biological effectsexposures, no known biological effects

�� Identifies range of disease Identifies range of disease –– increased CIMT, nonincreased CIMT, non--occlusive occlusive

plaque, stenosisplaque, stenosis

�� Normal values are known Normal values are known –– 2525--85 years old, both sexes, most 85 years old, both sexes, most

races/ethnicitiesraces/ethnicities

�� Predicts future MI, CHD death, and stroke, with incremental Predicts future MI, CHD death, and stroke, with incremental

predictive powerpredictive power

�� Track serial changesTrack serial changes

�� Recommended by NCEP ATP III, AHA, ACC, ASE, SVM, Recommended by NCEP ATP III, AHA, ACC, ASE, SVM, SAIP, and ESC to assist with CVD risk stratificationSAIP, and ESC to assist with CVD risk stratification

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Carotid Duplex ProtocolCarotid Duplex Protocol

�� Presence or absence of plaquePresence or absence of plaque

�� Morphology of plaqueMorphology of plaque

�� Calcified / Calcified / echolucentecholucent / heterogeneous/ heterogeneous

�� Degree of stenosisDegree of stenosis

�� Spectral Spectral dopplerdoppler (angle(angle--corrected) corrected)

�� Quantitative; measurement of hemodynamic changesQuantitative; measurement of hemodynamic changes

�� Peak systolic velocityPeak systolic velocity, end, end--diastolic velocity, ICA/CCA Ratiodiastolic velocity, ICA/CCA Ratio

�� Sensitivity ~85%, specificity ~90% Sensitivity ~85%, specificity ~90%

�� Similar to MRA for occlusion and stenosis > 70%Similar to MRA for occlusion and stenosis > 70%

Color Mode: Echolucent PlaqueColor Mode: Echolucent Plaque

Case 1Case 1

�� 50 year old female50 year old female�� HypertensionHypertension

�� Current smokerCurrent smoker

�� No DMNo DM

�� No known CAD No known CAD

�� TC 212 HDL 57 LDL 126 TG 144TC 212 HDL 57 LDL 126 TG 144

�� FRS 6%FRS 6%

�� Would the presence of carotid plaque on Would the presence of carotid plaque on ultrasound alter her management?ultrasound alter her management?

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How is Plaque Defined?How is Plaque Defined?

�� Focal wall thickening Focal wall thickening that is at least 50% that is at least 50% greater than that of greater than that of surrounding vessel wallsurrounding vessel wall

OROR

�� Focal thickening of IMTFocal thickening of IMTgreater than 1.5 mmgreater than 1.5 mm

Stein JH, et al.. J Am Soc Echocardiogr 2008.Stein JH, et al.. J Am Soc Echocardiogr 2008.Mannheim Consensus Cerebrovasc Dis 2007.Mannheim Consensus Cerebrovasc Dis 2007.

Carotid Plaque and CADCarotid Plaque and CAD

�� Patients with occlusive carotid disease 7 times Patients with occlusive carotid disease 7 times

more likely to have positive exercise stress test more likely to have positive exercise stress test

than patients with normal carotid arteriesthan patients with normal carotid arteries

�� Presence of carotid plaques associated with Presence of carotid plaques associated with

angiographic CAD angiographic CAD

�� MultiMulti--vessel CAD associated with higher vessel CAD associated with higher

prevalence of carotid plaque than singleprevalence of carotid plaque than single--vessel vessel

diseasedisease Bruckert E et al. Atherosclerosis 1992

Nowak J et al. Stroke 1998

Skaguchi M et al. Ultrasound Med Biol 2003

Prospective Studies Relating Carotid Plaque Prospective Studies Relating Carotid Plaque Presence to Incident CVD in Asymptomatic Presence to Incident CVD in Asymptomatic

IndividualsIndividualsStudyStudy NN AgeAge YrsYrs EventEvent Adjusted HR Adjusted HR

ARICARIC 12,37512,375 4545--6464 77MI, CHD MI, CHD deathdeath

2.96 (1.542.96 (1.54--3.30)3.30)

KIHDKIHD 1,2881,288 4242--6060 ≤2≤2 MIMI 4.15 (1.54.15 (1.5--11.47)11.47)

MDCSMDCS 5,1635,163 4646--6868 77MI, CHD MI, CHD deathdeath

1.81 (1.141.81 (1.14--2.87)2.87)

Northern Northern ManhattanManhattan

1,9391,939 >40>40 66 StrokeStroke 3.1 (1.13.1 (1.1--8.5)8.5)

RotterdamRotterdam 6,389 6,389 >55>55 77--1010 MIMI 1.83 (1.271.83 (1.27--2.62)2.62)

San San DanielleDanielle

1,3481,348 1818--9999 1212Stroke, TIA, Stroke, TIA,

vascular vascular deathdeath

10.4 (6.410.4 (6.4--17.1)17.1)

Yao CityYao City 1,2891,289 6060--7474 55 StrokeStroke 3.2 (1.43.2 (1.4--7.1)7.1)

Modified from Johnson HM, et al. J Nuc Cardiol 201 1;18:153Modified from Johnson HM, et al. J Nuc Cardiol 201 1;18:153

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Case 1 Carotid Duplex: Screen for plaqueCase 1 Carotid Duplex: Screen for plaque

Does Plaque Presence (Increased CV Risk) Does Plaque Presence (Increased CV Risk)

Justify Initiation of Preventive Therapies?Justify Initiation of Preventive Therapies?

�� Smoking cessationSmoking cessation

�� Smokers shown images of carotid plaques were more likely to Smokers shown images of carotid plaques were more likely to stop smoking at 6 monthsstop smoking at 6 months

�� Quit Rates 22% versus 6%, p=0.003 in those who had plaqueQuit Rates 22% versus 6%, p=0.003 in those who had plaque

Bovet P, et al. Bovet P, et al. PrevPrev Med 2002.Med 2002.

�� Lifestyle modificationLifestyle modification

�� Patients more likely to adhere to diet and exercise Patients more likely to adhere to diet and exercise

recommendations after seeing pictures of plaquerecommendations after seeing pictures of plaque

�� Would you initiate treatment with a statin?Would you initiate treatment with a statin?

�� What should be her target LDLWhat should be her target LDL--C?C?

“Less is “Less is NotNot More”More”

“PPIs for persons with nonulcer dyspepsia, opioid “PPIs for persons with nonulcer dyspepsia, opioid

medications for persons with chronic medications for persons with chronic

nonmalignant pain, and STATIN medications nonmalignant pain, and STATIN medications

for persons without CAD are all examples of the for persons without CAD are all examples of the

widespread use of medications with known widespread use of medications with known adverse effects despite the ABSENCE of adverse effects despite the ABSENCE of

DATA FOR PATIENT BENEFIT for these DATA FOR PATIENT BENEFIT for these

indications.”indications.”

Redberg R et al. Arch Intern Med. Dec 13 2010.

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Case 2Case 2

�� 43 year old female43 year old female

�� Family history of premature CHDFamily history of premature CHD

�� Father CABG at age 49, brother MI at age 47Father CABG at age 49, brother MI at age 47

�� No hypertension, no DMNo hypertension, no DM

�� NonNon--smokersmoker

�� TC 192, HDL 52, LDL 122, TG 92TC 192, HDL 52, LDL 122, TG 92

�� Framingham Risk < 1%Framingham Risk < 1%

Carotid Ultrasound: No PlaqueCarotid Ultrasound: No Plaque

Do CIMT MeasurementDo CIMT Measurement

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Carotid IntimaCarotid Intima--Media Thickness (IMT)Media Thickness (IMT)

US Measure of ATHUS Measure of ATH

EndotheliumEndothelium

Intima

Media

HIGH RESOLUTION

B-MODE ULTRASOUND

CCA

CCAbulb

bulb

Near wall

Far wall

IntimaMediaAdventitia

IntimaMediaAdventitia

Normal and Abnormal Carotid

Intima-Media Thickness

TOTAL IMT = Σ Σ Σ Σ IMT ii =1

n

where IMTi = Mean (A j – B j) or Max (A j – B j)

Aj

B jn

Plaquemeasured separately

IMTi

CAROTID IMT CALCULATION

Distal 1 cm of far wall of CCA

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Why Use the Distal CCA?Why Use the Distal CCA?

�� Size of vesselSize of vessel

�� Superficial locationSuperficial location

�� Ease of accessibilityEase of accessibility

�� In comparison to ICA and bulb which is more In comparison to ICA and bulb which is more

dependent on technical expertisedependent on technical expertise

�� Limited movementLimited movement

Stein JH, et al. ASE Consensus Statement. Stein JH, et al. ASE Consensus Statement. J Am Soc Echocardiogr 2008J Am Soc Echocardiogr 2008

Clinical CIMT MeasurementClinical CIMT Measurement

ASE Task Force

Recommendation

� Distal 1 cm of far wall of each CCA

� Obtain measurement and compare with values from

normative data set

Distribution of CIMT in the General Distribution of CIMT in the General

Population: ARIC StudyPopulation: ARIC Study

0.64 0.650.74

0.80.75 0.78

0.930.98

0.85 0.85

1.091.14

0

0.2

0.4

0.6

0.8

1

1.2

1.4

LCCA RCCA L Bulb R Bulb

0.72 0.71

0.84 0.850.83 0.84

1.03 1.040.99 1.01

1.311.21

0

0.2

0.4

0.6

0.8

1

1.2

1.4

LCCA RCCA L Bulb R Bulb

0.61 0.61

0.73 0.750.71 0.71

0.88 0.910.81

0.93

1.091.16

0

0.2

0.4

0.6

0.8

1

1.2

1.4

LCCA RCCA L Bulb R Bulb

0.70.66

0.82

0.66

0.8 0.77

1.06

0.77

0.93 0.9

1.23

0.9

0

0.2

0.4

0.6

0.8

1

1.2

1.4

LCCA RCCA L Bulb R Bulb

Black Women

White Women

Black Men

White Men

Howard G, et al Stroke 1993; 24:1297-1304

45 yrs

55 yrs65 yrs

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Distribution of CIMT in General Population: AXA Stu dyDistribution of CIMT in General Population: AXA Stu dy

Gariepy J et al Arterioscler Thromb Vasc Biol 1998

Modified from Johnson HM, et al. J Nuc Cardiol 201 1;18:153Modified from Johnson HM, et al. J Nuc Cardiol 201 1;18:153

Prospective Studies Relating CCA CIMT to Prospective Studies Relating CCA CIMT to Incident CVD Events in Asymptomatic IndividualsIncident CVD Events in Asymptomatic Individuals

StudyStudy NN AgeAge YrsYrs CV EventCV Event CutpointCutpoint Adjusted RR Adjusted RR (95% CI)(95% CI)

ARICARIC 12,84112,841 4545--6464 55 MI, CHD deathMI, CHD death tertiletertile W: 2.53 (1.02W: 2.53 (1.02--6.26) 6.26) M: 2.02 (1.32M: 2.02 (1.32--3.09)3.09)

14,21414,214 4545--64 64 77 strokestroke tertiletertile W: 2.32 (1.09W: 2.32 (1.09--4.94) 4.94) M: 2.24 (1.26M: 2.24 (1.26--4.00)4.00)

CAPSCAPS 5,0565,056 1919--9090 44 MI, stroke, deathMI, stroke, death quartilequartile 1.85 (1.091.85 (1.09--3.15)3.15)

CHSCHS 4,4764,476 >65>65 66 MIMI quintilequintile 3.61 (2.133.61 (2.13--6.11)6.11)

strokestroke quintilequintile 2.57 (1.642.57 (1.64--4.02)4.02)

KIHDKIHD 1,2571,257 4242--6060 33 MIMI >1.0 mm>1.0 mm 2.1 (0.82.1 (0.8--5.2)5.2)

MDCSMDCS 5,1635,163 4646--6868 77 MI, CHD deathMI, CHD death tertiletertile 1.50 (0.811.50 (0.81--2.59)2.59)

MESAMESA 6,698 6,698 4545--8484 44 CHD, CHD deathCHD, CHD death quartilequartile 2.3 (1.42.3 (1.4--3.8)3.8)

RotterdamRotterdam 6,389 6,389 >55>55 77--1010 MIMI quartilequartile 1.95 (1.191.95 (1.19--3.19)3.19)

San DanielleSan Danielle 1,3481,348 1818--9999 1212 Stroke, TIA, Stroke, TIA, vascular deathvascular death

>1.0 mm>1.0 mm 5.6 (3.25.6 (3.2--10.1)10.1)

TromsoTromso 6,2266,226 2525--8484 55 MIMI quartilequartile W: 2.86 (1.07W: 2.86 (1.07--7.65) 7.65) M: 1.73 (0.98M: 1.73 (0.98--3.06)3.06)

Yao CityYao City 1,2891,289 6060--7474 55 strokestroke quartilequartile 4.9 (1.94.9 (1.9--12.0)12.0)

CIMT Progression and Clinical CV EventsCIMT Progression and Clinical CV Events

Hodis HN, et al. Ann Intern Med 1998;128:262-9.

CIMT: R distal CCA far wall

RR 2.2 per 0.03 mm/year; P < 0.001

RRQ4/Q1 2.8

N=188

Non-

smoking

Men ages

45-59

Prior

CABG

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Clinical Trials: CClinical Trials: Carotid IMT as an outcome measurearotid IMT as an outcome measureCarotid IMT and StatinsCarotid IMT and Statins

Pravastatin:

PLAC-II (Pravastatin, Lipids, and Ath in Carotid Arteries)

KAPS (Kuopio Atherosclerosis Prevention Study)

REGRESS (Regression growth Evaluation Statin Study)

LIPID (Long-term Intervention with Pravastatin in Ischemic Dis)

Lovastatin:

MARS (Monitored Atherosclerosis Regression Study)

ACAPS (Asymptomatic Carotid Artery Progression Study)

*Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials

*NOT FDA-approved surrogate end point of vascular events

METEOR TrialMETEOR Trial

�� 984 subjects984 subjects

�� Age as only CVD risk factor (mean 57 yrs) ORAge as only CVD risk factor (mean 57 yrs) OR

�� FRS < 10%FRS < 10%

�� Modest CIMT thickening (focal CIMT > 1.2 mm)Modest CIMT thickening (focal CIMT > 1.2 mm)

�� Elevated LDLElevated LDL--C (range 120C (range 120--190 mg/dL)190 mg/dL)

�� Randomized to 40 mg rosuvastatin versus Randomized to 40 mg rosuvastatin versus

placeboplacebo

�� CIMT progression rate over 2 years assessedCIMT progression rate over 2 years assessed

Crouse, J. R. et al. JAMA 2007;297:1344-1353.

METEOR: Change in Maximum CIMT for the Primary End Point

∆ CIMTmax = ∆ CIMTmax = --0.0145 0.0145 mm/yearmm/year

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•3300 men and women with vascular disease

• HDL-C ≤ 40 (<50 F)• TG 150-400 • LDL-C ≤ 180

Simvastatin Simvastatin+Niacin

1° Endpoint: CHD Death, MI, CVA, or hi-risk ACS

hospitalization

AIM-HIGH Study Design

Equivalent Goal LDL

(AIM HIGH) Results(AIM HIGH) Results

�� 3414 subjects ; age 64; 34% with T2DM and 71% with MetS; 94% 3414 subjects ; age 64; 34% with T2DM and 71% with MetS; 94%

prior statinsprior statins

�� Randomized to simva to reduce LDLRandomized to simva to reduce LDL--C < 80 mg/dL; then niacin C < 80 mg/dL; then niacin

ER 2 gm in 1718 or PBO in 1696ER 2 gm in 1718 or PBO in 1696

�� Baseline lipids: LDLBaseline lipids: LDL--C 71C 71TG 161TG 161

HDL 35HDL 35

�� Primary endpoint composite: no difference after 32 months; trial Primary endpoint composite: no difference after 32 months; trial

stopped for futility after 511 events of 800 planned. stopped for futility after 511 events of 800 planned.

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CIMT ChallengesCIMT Challenges

�� Ultrasound protocol heterogeneityUltrasound protocol heterogeneity�� Image acquisition segment: CCA/Bulb/ICAImage acquisition segment: CCA/Bulb/ICA

�� Wall: near, farWall: near, far�� Type of measure: max, mean of max (2Type of measure: max, mean of max (2--12)12)

�� Unilateral or bilateralUnilateral or bilateral

�� Measurement variabilityMeasurement variability�� Scanning equipmentScanning equipment

�� SonographersSonographers�� Reading equipmentReading equipment�� ReadersReaders

�� Limited ReimbursementLimited Reimbursement

Back to Case 2Back to Case 2

�� 43 year old female43 year old female

�� Family history of premature CHDFamily history of premature CHD

�� Father CABG at age 49, brother MI at age 47Father CABG at age 49, brother MI at age 47

�� No hypertension, no DMNo hypertension, no DM

�� NonNon--smokersmoker

�� TC 192, HDL 52, LDL 122, TG 92TC 192, HDL 52, LDL 122, TG 92

�� Framingham Risk < 1%Framingham Risk < 1%

Case 2: CIMT MeasurementCase 2: CIMT Measurement

�� CIMT 0.70 mmCIMT 0.70 mm

�� Between 90Between 90thth and 95and 95thth

PrecentilesPrecentiles

�� CV Risk: CV Risk: IncreasedIncreased

�� Although FRS < 1%, Although FRS < 1%,

CIMT measurement CIMT measurement

indicates increased CV indicates increased CV

risk in this patientrisk in this patient

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ASE Consensus StatementASE Consensus Statement

Stein JH, et al. J Am Soc Echocardiogr 2008;21:93Stein JH, et al. J Am Soc Echocardiogr 2008;21:93

Who Should be Screened?Who Should be Screened?

�� Intermediate CVD risk Intermediate CVD risk

�� FRS 6%FRS 6%--20% without established CHD, DM20% without established CHD, DM

�� Family history of premature CVD in first degree Family history of premature CVD in first degree

relative (men < 55 years, women < 65 years)relative (men < 55 years, women < 65 years)

�� Women younger than 60 years with at least 2 Women younger than 60 years with at least 2

CVD risk factorsCVD risk factors

�� Not recommended in patients with established Not recommended in patients with established

atherosclerotic diseaseatherosclerotic disease

ASE Consensus Statement: CV RiskASE Consensus Statement: CV Risk

�� CVD Risk CVD Risk IncreasedIncreased�� If CIMT ≥ 75If CIMT ≥ 75thth percentile for age, race, sexpercentile for age, race, sex

�� If carotid plaque is presentIf carotid plaque is present�� Greater than 50% protrusionGreater than 50% protrusion

�� Focal IMT > 1.5 mmFocal IMT > 1.5 mm

�� CVD Risk CVD Risk Average (unchanged)Average (unchanged)�� CIMT in the 25CIMT in the 25thth to 75to 75thth percentilepercentile

�� CVD Risk CVD Risk LowerLower�� CIMT ≤ 25CIMT ≤ 25thth percentilepercentile

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Proposed Screening AlgorithmProposed Screening Algorithm

FRS 6%-20%Family History Premature CVD

F < 60 years with 2 CVD Risk Factors

SCREENING CAROTID DUPLEX

PLAQUE PRESENT

STOP

PLAQUE ABSENT

CIMT MEASUREMENT

ARIC Study: CIMT and Plaque in ARIC Study: CIMT and Plaque in

CHD Risk Prediction CHD Risk Prediction

�� 13,145 subjects free of CHD or stroke (4513,145 subjects free of CHD or stroke (45--65yr)65yr)

�� Mean follow up 15.1 yearsMean follow up 15.1 years

�� 1,812 incident CHD events1,812 incident CHD events

�� Risk Prediction Models (10Risk Prediction Models (10--yr CHD risk)yr CHD risk)

�� Traditional Risk Factors (TRF)Traditional Risk Factors (TRF)

�� TRF + CIMTTRF + CIMT

�� TRF + PlaqueTRF + Plaque

�� TRF + CIMT + PlaqueTRF + CIMT + Plaque

Nambi et al. JACC 2010;55:1600-7.

CIMT and Plaque DefinitionsCIMT and Plaque Definitions

�� CIMTCIMT

�� Mean of mean of distal CCA, bifurcation, and Mean of mean of distal CCA, bifurcation, and

proximal ICA measurements (both right and left)proximal ICA measurements (both right and left)

�� Categorized as: <25Categorized as: <25thth, 25, 25thth--7575thth, >75, >75thth percentilespercentiles

�� Plaque Plaque –– 2 of 3 criteria:2 of 3 criteria:

�� Abnormal wall thickness (CIMT > 1.5 mm)Abnormal wall thickness (CIMT > 1.5 mm)

�� Abnormal wall shape (protrusion into lumen)Abnormal wall shape (protrusion into lumen)

�� Abnormal wall texture (brighter echoes)Abnormal wall texture (brighter echoes)

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ARIC Results: CHD Incidence RateARIC Results: CHD Incidence Rate

Nambi et al. JACC 2010;55:1600-7

ARIC Results: Effect on AUCARIC Results: Effect on AUC

Nambi et al. JACC 2010;55:1600-7

ARIC: Reclassification of SubjectsARIC: Reclassification of Subjects

�� TRF + CIMT + Plaque resulted in reclassification of TRF + CIMT + Plaque resulted in reclassification of

~23% of subjects~23% of subjects

�� More subjects reclassified to lower risk groupMore subjects reclassified to lower risk group

�� 12.4% vs. 11% 12.4% vs. 11%

�� No subjects were reclassified from low (<5%) to high No subjects were reclassified from low (<5%) to high

risk (>20%)risk (>20%)

�� No subjects reclassified from high to low riskNo subjects reclassified from high to low risk

�� Results similar in FRSResults similar in FRS--based TRF modelbased TRF model

�� www.ARICnews.netwww.ARICnews.net (CHD risk calculator)(CHD risk calculator)

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2010 ACCF/AHA Guideline for Assessment 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic of Cardiovascular Risk in Asymptomatic

AdultsAdultsRecommendation for Measurement of Carotid Recommendation for Measurement of Carotid IntimaIntima--Media ThicknessMedia Thickness

CLASS IIa (Level of Evidence: B)CLASS IIa (Level of Evidence: B)

“Measurement of carotid artery intima“Measurement of carotid artery intima--media media thickness is reasonable for cardiovascular risk thickness is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate assessment in asymptomatic adults at intermediate risk (43,44). Published recommendations on risk (43,44). Published recommendations on required equipment, technical approach, and required equipment, technical approach, and operator training and experience for performance of operator training and experience for performance of the test must be carefully followed to achieve highthe test must be carefully followed to achieve high --quality results (44).quality results (44).

Greenland P, et al. J Am Coll Cardiol 2011 (in pres s)Greenland P, et al. J Am Coll Cardiol 2011 (in pres s)

ASE/SVM Consensus StatementASE/SVM Consensus Statement

•• Increased CVD risk ifIncreased CVD risk if–– CIMT CIMT ≥75≥75thth percentile for age, sex, racepercentile for age, sex, race

–– Presence of carotid plaque (> 50 % Presence of carotid plaque (> 50 % protrusion or focal IMT ≥1.5 mm)protrusion or focal IMT ≥1.5 mm)

•• Recommendations Recommendations –– Scanning techniqueScanning technique

–– InterpretationInterpretation

–– ReportingReporting

–– Training and certificationTraining and certificationStein JH, et al. J Am Soc Echocardiogr 2008;21:93Stein JH, et al. J Am Soc Echocardiogr 2008;21:93

ASE/SVM Consensus StatementASE/SVM Consensus StatementPatient SelectionPatient Selection

•• “Intermediate” risk“Intermediate” risk–– 1010--year Framingham risk of 6year Framingham risk of 6--20% 20% –– Not already at high risk Not already at high risk

•• Family history of premature CV disease in a Family history of premature CV disease in a firstfirst--degree relative (men <55, women <65 yo)degree relative (men <55, women <65 yo)

•• Younger people with severe abnormalities in a Younger people with severe abnormalities in a single risk factor who are not being treated single risk factor who are not being treated with medications (with medications ( e.g.,e.g., genetic dyslipidemia, genetic dyslipidemia, heavy smoker) heavy smoker)

•• Women <60 years old with Women <60 years old with ≥≥2 CV risk factors2 CV risk factorsStein JH, et al. J Am Soc Echocardiogr 2008;21:93Stein JH, et al. J Am Soc Echocardiogr 2008;21:93

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•• Level I: Level I: NoNo imaging testsimaging tests

•• Level Level IIaIIa: : CIMT, CAC, ECG (HTN/DM), CIMT, CAC, ECG (HTN/DM), ABIABI

•• Level Level IIbIIb: : TTE (HTN), stress ECG, TTE (HTN), stress ECG, stress MPI (DM/stress MPI (DM/FHxFHx/CAC>400)/CAC>400)

•• Level III: Level III: Brachial FMD, arterial Brachial FMD, arterial stiffness, CTA, MRA plaquestiffness, CTA, MRA plaque

Greenland P, et al. J Am Coll Cardiol 2011 (in pres s)Greenland P, et al. J Am Coll Cardiol 2011 (in pres s)

2010 ACCF/AHA Guideline for Assessment 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic of Cardiovascular Risk in Asymptomatic

AdultsAdults

Objective: To determine whether CIMT has added value

in the 10-year risk prediction (FRS) of first-time MI

or stroke.

Methods: Meta-analysis of 14 population based cohorts,

45,828 individuals median follow-up 11 years:

4,007 MI or strokes observed.

Only 5/14 studies

significant

association

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“… the added value of common CIMT measurements to the Framingham

risk score in the general population was small”: Of 45,828 individuals

from 14 cohort studies worldwide, 0.8% were correctly reclassified.

“In individuals at intermediate risk, the added value was 3.2% in men

and 3.9% in women. Our results suggest, that common CIMT measurements

should not be routinely performed in the general population because

the overall added value is small and unlikely to be of clinical importance”

Objective: to compare improvement in prediction of incident CHD

of 6 risk markers: 1) coronary artery calcium

2) IMT

3) ABI

4) brachial flow-mediated dilatation

5) hsCRP

6) FHx

Methods: 6814 MESA participants from 6 US field centers (1330

intermediate risk participants).

7.6 years follow-up: 94 CHD and 123 CVD events.

AUC and NRI were calculated.

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“Coronary artery calcium, ABI, hsCRP and family history were independent

predictors of incident CHF in intermediate-risk individuals. CAC provided

superior discrimination and risk reclassification compared with other risk

markers.”

“CIMT […] was not associated with incident CHD in multivariable analyses.”

Prospective cohort study, n=6698, age 45-84.

IMT and CAC measured at baseline in 6 field centers

Main outcome: risk of incident CVD (CAD, stroke, CVD death) over 5.3 yrs. of f/u.

MESA: CVD Prediction with CIMT and

CAC• Highest quartile CIMT predicted CVD events:

adjusted HR 2.3 (1.4 – 3.8) to 3.8 (2.2 – 6.4)

• But: adjusted HR higher with CAC (6.0, 3.9 – 9.1)

• Risk factors = 0.772

• RFs + CIMT = 0.782

• RFs + CAC = 0.808

• RFs + CIMT + CAC = 0.811

• CIMT predicted stroke (HRSD = 1.3, p=0.01), but CAC

did not (HRSD = 1.1, p=0.71)Folsom AR, et al. Arch Intern Med 2008;168:1333Folsom AR, et al. Arch Intern Med 2008;168:1333

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Objective: To compare improvement in prediction of incident CHD

with addition of CIMT to Framingham Risk Score

Methods: Mean IMT of ICA and CCA in 2965 participants of

Framingham Offspring Study were measured.

7.2 years follow-up: 296 cardiovascular events.

C-statistic and NRI were calculated.

“We conclude that the intima-media thickness of the common

carotic artery and the intima-media thickness of the ICA are

independent predictors of cardiovascular events among participants

in the Framingham Offspring Study.”

“The maximum intima-media thickness of the ICA, […], contributed

significantly but modestly to the predictive power of the risk factors

used in calculating the FRS and improved risk classification on the

basis of the FRS.”

Unanswered Questions and Future DirectionsUnanswered Questions and Future Directions

�� No study has shown that treatment based on carotid No study has shown that treatment based on carotid

plaque presence or CIMT alters longplaque presence or CIMT alters long--term outcomesterm outcomes

�� Does plaque screening and subsequent intensification Does plaque screening and subsequent intensification

of medical regimens in patients with plaque or of medical regimens in patients with plaque or

increased CIMT prevent cardiovascular events?increased CIMT prevent cardiovascular events?

�� Is this costIs this cost--effective?effective?

�� Need prospective studies to determine effectiveness of Need prospective studies to determine effectiveness of

carotid ultrasound imaging in improving CVD carotid ultrasound imaging in improving CVD

outcomesoutcomes

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• For example:

• Established Atherosclerotic CVD

• FRS, RRS, or Global Risk ≥10%

• Most patients w/ DM or CKD

• CAC>100

High10-Year

Risk

High10-Year

Risk

• For example:

• Age ≥50 + major RF

• FRS, RRS, or Global Risk 5-10%

• CAC>0 + ≤100

• FHx or MetS + age >40 years ���� Consider CAC scan

High Lifetime

Risk

High Lifetime

Risk

• None of above

• 10-yr risk <5%

• Lifetime risk <39%

LowRiskLowRisk

Lifestyle Changes

+

Potent Statin

Lifestyle Changes

+

Discuss Statin

Focus on

Ideal CV Health