Prevention of Cardiovascular Disease: Screening for Atherosclerosis Nathan D. Wong, PhD, FACCProfessor and DirectorHeart Disease Prevention ProgramDivision of CardiologyUniversity of CA, Irvine

ATP III Assessment of CHD RiskFor persons without known CHD, other forms of atherosclerotic disease, or diabetes:Count the number of risk factors:Cigarette smokingHypertension (BP 140/90 mmHg or on antihypertensive medication)Low HDL cholesterol (

Assessing CHD Risk in MenNote: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.Step 2: Total Cholesterol TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79

Modified approach to CHD risk assessmentLOW RISK designated as

PresentationExamination:Height: 6 ft 2 inWeight: 220 lb (BMI 28 kg/m2)Waist circumference: 41 inBP: 150/88 mm HgP: 64 bpm RR: 12 breaths/minCardiopulmonary exam: normalLaboratory results: TC: 220 mg/dLHDL-C: 36 mg/dLLDL-C: 140 mg/dLTG: 220 mg/dLFBS: 120 mg/dL

What is WJCs 10-year absolute riskof fatal/nonfatal MI?

A 12% absolute risk is derived from points assigned in Framingham Risk Scoring to:Age: 6TC: 3HDL-C: 2SBP: 2Total: 13 points

In 1992 he exercised 14 minutes in a Bruce protocol exercise stress test to 91% of his maximum predicted heart rate without any abnormal ECG changes. He started on a statin in 2001. But in Sept 2004, he needed urgent coronary bypass surgery.

The Detection Gap in CHDDespite many available risk assessment approaches, a substantial gap remains in the detection of asymptomatic individuals who ultimately develop CHDThe Framingham and European risk scores emphasize the classic CHD risk factors. is only moderately accurate for the prediction of short- and long-term risk of manifesting a major coronary artery eventPasternak and Abrams et al. 34th Bethesda conf. JACC 2003; 41: 1855-1917

Most Myocardial Infarctions Are Causedby Low-Grade StenosesPooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al, 1992. (Adapted from Falk et al.)Falk E et al, Circulation, 1995.

Coronary Remodeling(Adapted from Glagov et al.)NormalvesselMinimalCADProgressionCompensatory expansionmaintains constant lumenExpansion overcome:lumen narrowsSevereCADModerateCADGlagov et al, N Engl J Med, 1987.

How Good Is NCEP III in Identifying Patients at Risk for MI1998 2002. 222 patients with 1st acute MI, no prior CAD, no DM. Men

Total Cholesterol Distribution: CHD vs Non-CHD PopulationCastelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.1996 Reprinted with permission from Elsevier Science.35% of CHD Occurs in People with TC

Criteria required for a good screening testProvides an accurate determination of the likelihood that an asymptomatic person has the condition (accuracy)Reproducible results (reliability)Detect individuals where early intervention is likely to have a beneficial impactShould provide incremental value to risk predicted by office-based risk assessment

Redberg and Vogel et al., 34th Bethesda Conf. JACC 2003; 41: 1855-1917

Potential benefits of screening for subclinical atherosclerosisImproved diagnosis: the goal of CVD screening is to accurately determine risk early in the natural history of diseaseAdding subclinical disease markers to traditional CVD risk factor screening can identify the subset of individuals at increased risk of CVD outcomesThis can facilitate more appropriate, targeted interventions that will further reduce CVD morbidity and mortalityWilson PWF, Smith SC, Blumenthal RS, Burke GL, Wong ND, Task force 4, 34th Bethesda Conference, JACC 2003; 41: 1898-1905

Who should be screened for atherosclerosis?

Who should be screened?AHA Prevention V (Greenland et al., Circ. 2000) indicated persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US for those over age 50 years, and coronary calcium screening.Patients at intermediate risk .have at least 1 major risk CHD factor and a 6-20% 10-year risk of a hard CHD event, possibly warranting further risk stratification by noninvasive tests to assess atherosclerotic burden (Wilson and Smith et al. Task force 4, 34th Bethesda Conference, JACC 2003; 41: 1898-1905).Testing, if and when appropriate, should be accessed by physician referral, rather than self-referral as a result of commercial advertising

Carotid B-Mode UltrasonographyMeasurement of intimal medial thicknessNon-invasive, inexpensive, no radiationWell-established as an indicator of cardiovascular risk from epidemiologic studiesPublished clinical trials on utility of carotid IMT as measure of progression of atherosclerosis and effects of therapyAccuracy of assessments depends on experience of those interpreting scans

Devine JNC 2006;13: 710-8Intimal medial thickness over timeApproximate 75th % for age and gender

Cardiovascular Health Study: Combined intimal-medial thickness predicts total MI and strokeCardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7 years in those at highest quintile of combined IMT (OLeary et al. 1999)

The Rotterdam study: combined IMT by quartile risk of MIIglasias del Sol. Eur Heart J 2002;23:934-40Adjusted for age, gender, BMI, BP, Total Chol, HDL, smoking & DM12.33.14.8Case control study mean age 71 yrs; n = 194 MIs

ARBITER 2: Primary Endpoint Carotid IMT Across 12 Months CIMT at 12 monthsStatin vs ER niacin + statin P = 0.08Intent-to-treat analysis of statin vs. ER niacin + statin P = 0.048Non-Insulin resistant pts only: statin vs. ER niacin P = 0.026

Taylor AJ, et al. ARBITER 2: A double-blind, placebo-controlled study of extended-release niacin on Atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 200468% decrease in progression

2002, Professional Postgraduate Serviceswww.lipidhealth.org

Ankle-brachial blood pressure (ABI)

Simple noninvasive test to confirm lower extremity peripheral arterial disease (PAD)Uses Doppler probe to measure SBP in brachial, posterial tibial, and dorsalis pedis arteriesABI

Newman A et al ATVB 1999Ankle Brachial Index as a Predictor of Cardiovascular Mortality in the CHS Study

Coronary Calcium and Atherosclerosis: Pathology EvidenceCoronary calcium invariably indicates the presence of atherosclerosis, but atherosclerotic lesions do not always contain calcium (1-3).Calcium deposition may occur early in life, as early as the second decade, and in lesions that are not advanced (4-5).Correlates with plaque burden; highly sensitive for angiographic disease

1) Wexler et al., Circ 1996; 94: 1175-92, 2) Blankenhorn and Stern, Am J Roentgenol 1959; 81: 772-7, 3) Blankenhorn and Stern, Am J Med Sci 1961; 42: 1-49, 4) Stary, Eur Heart J 1990; 11(suppl E): 3-19, 5) Stary, Arteriosclerosis 1989; 9 (suppl I): 19-32.

Negative Predictive Power of EBT1764 persons underwent EBT and angiogramSensitivity for Obstruction (any calcium) 99.4% in men, 100% in womenNegative predictive power > 99%Can be used as a filter prior to angiography to help avoid negative angiograms

Haberl et al. JACC. 2001;37(Suppl2):A412-3.

Example of Significant Coronary Calcification from Multidetector CT (Siemens Sensation 64) scanner

Prevalence (%) of Coronary Calcium: US Adults Ages 45-84 Years (The MESA Study). Source: Bild et al., Circulation. 2005;111:1313-1320.

Chart2

70.444.6

52.136.5

56.534.9

59.241.9

Men

Women

Proportion (%) With Detectable Calcium

OVERWT

1960-621971-741976-801988-942001-2004

Men10.712.212.820.630.2

Women15.716.817.126.034.0

Age-Adjusted Prevalence of Obesity* in Adults Ages 20-74 by Sex and Survey

NHES and NHANES: 1960--62, 1971--74, 1976--80, 1988--94 and 2001-2004

Source:Health US, 2007

Obesity is defined as BMI of 30 plus.

OVERWT

1960-62

1971-74

1976-80

1988-94

2001-2004

Percent of Population

cholchild

Trends in Mean Total Blood Cholesterol Among Adolescents Ages 12-17 by Sex and Race and Survey

NHANES:1976-80,1988-94, 1999-02, 2003-04 and 2005-06

1976-801988-941999-022003-042005-06

White Males163163155156151

Black Males171165166161161

White Females170166163164163

Black Females172174168161160

Mex. Am. Males157158

Mex. Am. Females158161

cholchild

11

#REF!

#REF!

Percent of Population

diabetes

1976-80

1988-94

1999-02

2003-04

2005-06

Mean Total Blood Cholesterol

Hdl&Ldl

NH WhitesNH BlacksMexican Americans

Men5.814.911.3

Women6.113.114.2

Age-Adjusted Prevalence of Physician-Diagnosed Diabetes in Adults Age 20 and Older by Sex and Race/Ethnicity

NHANES: 2005-2006

NH WhitesNH BlacksMexican Americans

Less than high school8.115.313.0

High school6.117.512.2

More than high school5.410.812.0

Prevalence of Physician Diagnosed Type 2 Diabetes in Americans Age 18+

by Education, Race/Ethnicity and Years of Education

NHANES: 2005-2006

`

NCHS and NHLBI.

MaleFemale

Physician diagnosed 1988-945.45.4

Undiagnosed 1988-943.42.5

Physician diagnosed 2005-067.48.0

Undiagnosed 2005-063.82.1

Trends in Diabetes Prevalence in Adults Age 20 and Older, By Sex

NHANES: 1988-94 and 2005-2006

Source: NCHS and NHLBI.

Hdl&Ldl

NH Whites

NH Blacks

Mexican Americans

Percent of Population

smokhschool

Less than high school

High school

More than high school

Percent of Population

Metsyndr.

Male

Female

Percent of Population

PhysicAct.

Estiamted % of Americans Age 20 and Over with High-Risk LDL-Cholesterol of 130 mg/dL or More by Race and Sex

MenWomen

Total Population32.032.0

NH Whites32.034.0

NH Blacks32.030.0

Mexican Americans39.031.0

Age-Adjusted Prevalence of Americans Age 20 and Older With

LDL-Cholesterol of 130 mg/dL or Higher by Race/Ethnicity and Sex

United States: 2003-04

MenWomen

Total259

NH Whites269

NH Blacks167

Mexican Americans2813

Estimated Age-Adjusted (2000) Prevalence of Adults Age 20 and Over With

HDL-Cholesterol Under 40 mg/dL by Race and Sex

United States: NHANES 2003-2004

PhysicAct.

Men

Women

Percent of Population

smokmf

Men

Women

Percent of Population

NHANESrf

`NH WhitesNH BlacksHispanics

Males23.814.918.7

Females22.58.414.6

Prevalence of High School Students in Grades 9-12 Reporting Current Cigarette Use

Within the last 30 days by Race/Ethnicity and Sex

YRBS: 2007

NHANESrf

Males

Females

Percent of Population

oweightchild

CHD MortalityCVD MortalityTotal Mortality

No MetS or DM2.65.314.4

MetS w/o DM4.37.817.1

MetS w/DM4.88.621.1

DM only6.311.526.1

Prior CVD10.916.730.0

Prior CVD and DM17.028.144.1

Total Mortality Rates in US Adults Age 30-75, with Metabolic Syndrome, With and Without Diabetes and Pre-Existing CVD

NHANES1976-80 Follow-Up Study

oweightchild

No MetS or DM

MetS w/o DM

MetS w/DM

DM only

Prior CVD

Prior CVD and DM

Deaths/1,000 Person Years

RFNHANES

NH WhiteNH BlackHispanic

Male46.141.338.6

Female27.921.021.9

Prevalence of Students in Grades 9-12 Who Met Currently Recommended Levels of

Physical Activity During the Past 7 Days by Race/Ethnicity and Sex

YRBS: 2007Centers for disease control and Prevention. Youth risk Behavior Surveillance - United States, 2007. MMWR 2008;57(ss#4)

Men '01Women '01Men '05Women '05

NH White50.646.052.349.6

NH Black40.331.445.336.1

Hispanic42.036.341.940.5

Other race43.141.245.746.6

Prevalence of Leisure-Time Physical Activity Among Adults Age 18+ by Race/Ethnicity, and Sex

BRFSS: 2001, 2005

MMWR, vol.56, no.46, 11/23/07.

NH WhiteNH BlackHispanic

Male16.721.818.8

Female28.242.135.2

Prevalence of Students in Grades 9-12 Who Did Not Meet Currently Recommended Levels of

Moderate-to-Vigorous Physical Activity During the Past 7 Days by Race/Ethnicity and Sex

YRBS: 2007"Currently recommended levels" are defined as activity that increases heart rates and made them breathe hard some of the time for a total of >60 or more minutes/day on >5 or more out of 7 days predeeding the survey.

6-1112-1516-19

Male48.911.910.020-2930-3940-4950-5960-6970+

Female34.73.45.4Male10.39.99.37.16.53.5

Female7.46.56.65.75.82.2

Prevalence of Children Ages 6-19 Who Attained sufficient MVPA to Meet Public Health Recommendations of >60 or More

Minutes/Day on >5 or more of 7 Days by Sex and AgeMean Minutes/Day of MVPA in Bouts of 10+ Minutes by Sex and Age

NHANES 2003-2004

Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical Activity in the United States Measured by Accerometer. MSSE 2008; 40: 181-188.

Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical Activity in the United States Measured by Accerometer. MSSE 2008; 40: 181-188.

RFNHANES

NH White

NH Black

Hispanic

Percent of Population

choladults

Men '01

Women '01

Men '05

Women '05

Percent of Population

Hispanicrisk

NH White

NH Black

Hispanic

Percent of Population

CHDlowrisk

6-11

12-15

16-19

Percent of Population

SubclinicalDLJ

20-29

30-39

40-49

50-59

60-69

70+

Mean Minutes/Day

Subclinical

1212

Under 89-111213-1516 and UpWhites76.644.218.2Whites60.649.120.1

Men27.739.731.526.611.5Blacks26.724.116.4Blacks34.314.112.8

Women16.734.324.122.811.2Mexican Americans34.317.317.5Mexican Americans12.219.510.3

Prevalence of Current Smoking for Men Ages 18-24 by Education and Race/EthnicityPrevalence of Current Smoking for Women Ages 18-24 by Education and Race/Ethnicity

Current Cigarette Smoking for Adults Age 18 and Over by Education and SexUnited States: 1988-94United States: 1988-94

United States: 1998

Non-Hispanic White MenNon-Hispanic White WomenNon-Hispanic Black MenNon-Hispanic Black WomenHispanic MenHispanic WomenMenWomen

Risk Factor Indicators of Coronary, Thoracic Aortic, and Aortic Valve Calcium (Wong et al., Am J Cardiol Oct 2003)

Risk of Total Cardiovascular Events by Calcium Quartile (n=881)(compared to those with no calcium; age and risk-factor adjusted)

Wong ND et al., Am J Cardio 1995; 86: 295-8

Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic Individuals Shaw LJ et al., Radiology 2003; 228: 826-33

n=1,302n=5,876n=3,194Event rateShaw L, Raggi P et al. Radiology 2003;228:826-33.Risk of All Cause Mortality in Framingham Risk CategoriesCAC score

Cumulative Incidence of Any Coronary Event: MESA Study (Detrano et al., NEJM 2008)

Risk Factor-Adjusted Hazard Ratios by Coronary Calcium Score: MESA Study (Detrano et al., NEJM 2008)

Area Under Curve for Risk Factors Alone and Risk Factors Plus CAC by Ethnic Group: MESA Study (Detrano et al., NEJM 2008)

Indications for CAC Assessment: AHA Scientific Statement: Assessment of Coronary Artery Disease by Cardiac CT (Budoff et al., Circulation 2006; 114: 1761-1791)In clinically selected intermediate-risk patients, it may be reasonable to measure the atherosclerosis burden using EBCT or MDCT to refine clinical risk prediction and to select patients for more aggressive target values for lipid-lowering therapy(Class IIb, Level of Evidence: B)

Indications for CAC Assessment (cont.)May be reasonable for assessment of symptomatic patients, especially in the setting of equivocal treadmill or functional testing (Class IIb, Level of Evidence: B)May also be considered in the symptomatic patient fo determine the cause of cardiomyopathy or in those with chest pain with equivocal or normal ECGs and negative cardiac enzymes (Class IIb, Level of Evidence: B)

ACCF/AHA 2007 Clinical Expert Consensus Document (Greenland et al., JACC 2007: 49: 378-402)Reasonable to consider use of CAC measurements in those at intermediate CHD risk (10-20% 10-year CHD risk); such patients might be reclassified to a higher risk status based on a high CAC scoreDoes not recommend CAC screening in those at low (

The potential use of cardiac CT for assessing changes in plaque over time requires additional validation.Serial CT imaging for assessment of progression of coronary calcification (or use of CT angiography to track atherosclerosis over time) is not indicated at this time(Class III, Level of Evidence: C)AHA Scientific Statement: Assessment of Coronary Artery Disease by Cardiac CT (Budoff et al., Circulation 2006; 114: 1761-1791) and ACCF/AHA 2007 Consensus Document (Greenland et al, JACC, 2007)Recommendations for Serial CT Imaging

Calcium Score GuidelinesRumberger et al. Mayo Clin Proc 1999; 74: 243-52

Calcium ScorePlaque BurdenProbability of Significant CADImplications for CV RiskRecommendations0No identifiable PlaqueVery low, generally 50% of at least one significant coronary stenosisHighInstitute very aggressive risk factor modification. Consider exercise for pharmacologic nuclear stress testing to evaluate for inducible ischemia. Daily ASA.

Wong ND et al., JACC Imaging 2009

Wong ND et al., JACC Imaging 2009

TAC does not add to prediction of CVD over CAC and/or Framingham Risk Score (Wong ND et al., JACC Imaging 2009)

Abdominal Aortic Calcium (5cm from iliac bifurcation)

Prevalence of AAC (>0), CAC (>0), ABI (1mm) by Age in Men (Wong et al., AHA 2006)P

Prevalence of AAC (>0), CAC (>0), ABI (1mm) by Age in Women (Wong et al., AHA 2006)P

Flow Diagram Showing Interaction Between EBCT Results and Clinical Management (Taylor et al., Western J Med 1999; 171: 339-41)

SHAPE: Screening for Heart Attack Prevention and EducationAssociation for the Eradication of Heart Attack (AEHA) Am J Cardiol July 2006

Frequency of Abnormal SPECT According to CCSp

Comparison of ROC AreasSensitivity1-SpecificityBerman and Wong et al., J Am Coll Cardiol 2004; 44: 923-930.

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M11.ROC, Area = 0.7360, SE=0.0304

M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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M22.ROC, Area = 0.6519, SE=0.0305

M33.ROC, Area = 0.7216, SE=0.0285

M44.ROC, Area = 0.7828, SE=0.0262

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Age, gender, CRF, log(CCS+1)

Area=80%, SE=.03

Age, gender, CRF

Area=74%, SE=.03

Age, gender

Area=66%, SE=.03

log(CCS+1)

Area=76%, SE=.03

Prevalence of Inducible Ischemia Associated with Presence of Metabolic Abnormality and Coronary Calcium Score (Wong et al., Diabetes Care 2005; 28: 1445-50 )P

Metabolic Syndrome Independently Predicts Inducible Ischemia from SPECT (Wong ND et al., Diabetes Care 2005; 28: 1445-50 )*Estimates adjusted for age, gender, cholesterol and smoking. Odds of ischemia for metabolic abnormalities (yes vs. no) (separate model): 1.98 (1.20-3.98), p=0.008

Combined MPO-CAC Groups and CVD Event Risk (%)Wong ND et al., JACC Imaging 2009 (in press)Log-rank test for trend P

Using Global Risk Assessment in Combination with Subclinical Disease Screening: Proportion of Persons Identified with the Metabolic Syndrome at >20% 10-Year Estimated Risk of CHD and/or Significant Calcium (CAC) (>75th percentile)Wong et al., J Am Coll Cardiol 2003; 41: 1547-53

Proportion of Not Qualifying For Pharmacotherapy by NCEP-III across Increasing CACSNasir, Michos. Blumenthal, Raggi JACC 2005;193101936

CCS=0

CCS 1-99

CCS 100-399

CCS(400

40

50

60

70

80

90

100

89

74

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In 703 men and women aged 28-84 who received scanning for coronary calcium by EBCT, calcium score remained independently associated with: new aspirin usage new cholesterol medication consulting with a physician losing weight decreasing dietary fat but also increased worry

..potentially important risk-reducing behaviors may be reinforced by the knowledge of a positive coronary artery scan, independent of preexisting coronary risk factor status. Wong ND et al, Am J Cardiol. 1996 Dec 1;78(11):1220-3. Does coronary artery screening by electron beam computed tomography motivate potentially beneficial lifestyle behaviors?

Plaque burden vs. vulnerable plaque. Coronary calcification correlates with the magnitude of plaque burden, but does not offer further association with plaque vulnerability. Although the need to identify vulnerable plaque (beyond detecting the vulnerable patient) has not found universal acceptance, we believe that it will constitute one of the most important developments in our fight against acute coronary events.Narula J et al., Picking Plaques That Pop J Am Coll Cardiol 2005; 45: 1970-1972

Components of atherosclerosis that form targets for atherosclerosis imagingNecrotic core present in approx. 25% of plaques with 70% narrowingFibrous cap atheromas plaques with a lipid core covered by a fibrous capCalcium excellent correlation to plaque burden; almost always present in segments with obstructive disease, but weaker correlation with percent stenosis and could indicate stability of the plaque that is calcifiedInflammatory activity increases with increasing percent stenosisBurke and Virmani et al., 34th Bethesda conf., JACC 2003; 41: 1874-85

A vulnerable plaque scoring system? Is the sum greater than the parts?While there is no available vulnerable plaque scoring system, such a system to predict overall vulnerability could be a 10-point system based on three tiers of scoring the following characteristics:1) fibrous cap thickness2) necrotic core size (percent cross sectional plaque area and length) 3) degree of macrophage infiltrationNeed outcome studies showing CHD event prediction Burke and Virmani et al., 34th Bethesda Conf., JACC 2003; 41: 1855-917

Pathologic characteristics of ruptured plaquesThin fibrous cap (25% of plaque areaVessel remodeling, increased IELPlaque size, >50% occlusion in 4/5NeovascularizationIntraplaque hemorrhage

Narula J et al., Picking Plaques That Pop J Am Coll Cardiol 2005; 45: 1970-1972

3D vessel probe of the Left Main and LAD coronary artery. Curved MPR images are automatically rendered and quantify this LAD lesion at 48% diameter stenosis. SUREPlaque software is used to determine plaque burden and a vessel remodeling index at this lesion. Images courtesy of Courtesy of Toshiba America Medical Systems and Vital Images SUREPlaque and University of California Irvine, Cardiac CT Center.CT Angiography:Will total or non-calcified plaque burden predict CHD risk over standard risk factors or coronary calcium???

Indications for CT AngiographyMay be reasonable for assessment of symptomatic patients for the assessment of obstructive disease (Class IIb, Level of Evidence: B) but not for follow-up of stent placement (Class III, Level of Evidence: C)

The higher radiation dosages (up to 1.5 mSv with EBCT and 13 mSv with MDCT) contraindicate its use as a screening tool for asymptomatic patients (Class III, Level of Evidence: C)

AHA Scientific Statement: Assessment of Coronary Artery Disease by Cardiac CT (Budoff et al., Circulation 2006; 114: 1761-1791)

Noninvasive Aortic and Carotid Magnetic Resonance Image (MRI) ImagingCan identify plaque components such as fibrous cap, lipid core, calcium, hemorrhage, and thrombosis (vunerable plaques have thin fibrous cap and large lipid core)Non-invasive and no radiationComputerized morphometric analysis involves following edge of significant contrast, measuring total vascular and lumen area (difference being vessel wall area)Image-specific error of 2.6% for aortic and 3.5% for carotid plaques - allows measurement of changes in plaque (Corti et al., 2001)

Carotid Artery Localization and ImagingSequence:2D-TOFPDWT2WT1W3D-TOFDynamic GADPost-GAD T1W

Atherosclerotic plaque burden: lumen, wall & outer wall volume in mm3 wall/outer wall ratio wall thickness in mm**Tissue characteristics: volume in mm3 & composition in % of lipid, loose matrix, calcium, hemorrhage and fibrous tissueQuantitative MRI MeasurementsPlaque integrity evaluation: Cap - rapture, thin, and thick (quantified)Ulceration - no, yes and sizeThrombus - no, yes and size

In Vivo MRI imaging of Coronary Artery PlaqueDifficulties include cardiac and respiratory motion, nonlinear course of coronary arteries, and small size and location of coronary arteries.Inter- and intraobserver variability assessed by intraclass correlation ranged from 0.96-0.99.Wall thickness in human coronaries can be differentiated between normal and >40% stenosis; breathholding can minimize respiratory motion.Fayad and Fuster, Am J Cardiol 2001; 88 (suppl): 42E-45E.

MRI Serial T2-Weighted Images During Simvastatin Treatment: Coronary vessels (top) and descending aorta (bottom)(Corti et al., Circulation 2001; 104: 249-52)At 12 months (but not 6 months), significant reductions in vessel wall thickness and area (8% reduction in aorta and 15% reduction in carotid artery vessel wall area), without lumen area changes, were observed.

MRI assessment of plaque: ready for prime time?Limited to highly specialized research centersDefinition of an abnormal result is neededImproved resolution and techniques to quantify plaque components are neededNovel techniques for imaging vulnerable plaque are being developedNot yet recommended for use as a screening tool

SummaryTraditional global risk assessment approaches (e.g., NCEP, Framingham risk scores) are limited in their ability to identify persons at significant risk of CVD eventsThere are several modalities available to screen for atherosclerosis, each with its own advantages and disadvantages and extent of research validating criteria for a good screening test.Subclinical atherosclerosis screening may identify higher risk subsets who could benefit from more aggressive diagnostic evaluation and clinical management.

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Slide 3. Total cholesterol distribution: CHD vs non-CHD populationIn the Framingham Heart Study, as many as one third of all coronary heart disease (CHD) events occurred in individuals with total cholesterol