The Role of Imaging Coronary The Role of Imaging Coronary CalciumCalcium

Harvey S. Hecht, MD, FACC

Director of Preventive Cardiology

Beth Israel Medical Center & Continuum Heart Institute

Professor of Clinical Medicine

Albert Einstein College of Medicine

Need for Drug Therapy in Younger Adults with First MI Need for Drug Therapy in Younger Adults with First MI by NCEP III Guidelinesby NCEP III Guidelines

0102030405060708090

100 No Drug RxDrug Rx

>20%>20%2+RF2+RF

10-20%10-20%2+RF2+RF

<10%<10%2+RF2+RF

0-1RF0-1RF TotalTotal MenMen WomenWomen

Perc

enta

gePe

rcen

tage

Framingham Risk ScoreFramingham Risk Score

222pts: Men 222pts: Men <<55, Women 55, Women <<6565Age 50Age 50++7 ; 75% Men, 25% Women7 ; 75% Men, 25% Women

Akosah et al. JACC:2003;41:1475-9Akosah et al. JACC:2003;41:1475-9

0

5

10

15

20

25

30

35

<100100-129130-159>160

Need for Drug Therapy in Younger Adults with First Need for Drug Therapy in Younger Adults with First MI by NCEP III GuidelinesMI by NCEP III Guidelines

Framingham Risk ScoreFramingham Risk Score

Perc

enta

gePe

rcen

tage

>20%>20%2+RF2+RF

10-20%10-20%2+RF2+RF

<10%<10%2+RF2+RF

0-1 RF0-1 RF TotalTotal

222pts: Men 222pts: Men <<55, Women 55, Women <<6565Age 50Age 50++7 ; 75% Men, 25% Women7 ; 75% Men, 25% Women

Akosah et al. JACC:2003;41:1475-9Akosah et al. JACC:2003;41:1475-9

LDLLDL

12%12% 18%18%

20%20%

50%50%

Importance of Primary Prevention of CADImportance of Primary Prevention of CAD• Each year 1.1 million people have MI

– First symptomsymptom: MI: 500,000 Sudden deathSudden death: 150,000 “: 150,000 “the last symptomthe last symptom” ” – 63% of women and 50% of men with “sudden 63% of women and 50% of men with “sudden cardiac death” hadcardiac death” had no no prior known CAD prior known CAD

• 68% of MI’s occur due to a lesion representing 68% of MI’s occur due to a lesion representing <50%<50%stenosisstenosis

• 35% of patients with CAD have a total cholesterol 35% of patients with CAD have a total cholesterol <200<200

Examples of Coronary Artery ScansExamples of Coronary Artery Scans

Normal ConditionNormal Condition Moderate Moderate CalcificationCalcification

Severe CalcificationSevere Calcification

EBT, Arteriography and IVUSEBT, Arteriography and IVUS

0

2

4

6

8

10

12

14

16

0 1 2 3 4 5 6 7

Square Root Sum of Calcium AreasSqua

re R

oot

Sum

of P

laqu

e Ar

eas Sum of Coronary Calcium Areas vs.Sum of Coronary Calcium Areas vs.

Sum of Atherosclerotic Plaque AreasSum of Atherosclerotic Plaque Areasfor Individual Coronary Arteriesfor Individual Coronary Arteries

Rumberger, Circ 1995:92:2157-62Rumberger, Circ 1995:92:2157-62

n = 38n = 38

r = 0.90r = 0.90

p < .001p < .001

1121

44

7285

94

6 1123

35

67

89100 100

0

20

40

60

80

100

20-29 30-39 40-49 50-59 60-69 70-79 80-89

Age by Decade (years)

Perc

ent

(%)

Inci

denc

e Men (%) Women (%)

Incidence of Identifiable Coronary Calcium by EBTIncidence of Identifiable Coronary Calcium by EBTin a Group of Asymptomatic Men and Womenin a Group of Asymptomatic Men and Women

Janowitz, et al, AJC 1993

MEN (n=28,250)

EBCT Coronary Calcium Scores in Asymptomatic Patients as a Function of Patient Age at the Time of the Examination

Percentiles/Age (yrs)

40-45 46-50 51-55 56-60 61-65 66-70 70+

10 0 0 0 1 1 3 3 25 0 1 2 5 12 30 69 50 2 3 15 54 117 166 350 75 11 36 110 229 386 538 844 90

69 151 346 588 933 1151 1650

WOMEN (n=14,540)

10 0 0 0 0 0 0 0 25 0 0 0 0 0 1 4 50 0 0 1 1 3 25 51 75 1 2 6 22 68 148 231 90 4 21 61 127 208 327 698

EBT Coronary Calcium Scores as Function of Patient EBT Coronary Calcium Scores as Function of Patient Age and Gender – Results of National DatabaseAge and Gender – Results of National Database

EBT and Cardiovascular EventsEBT and Cardiovascular Events

Conclusion: Patients with coronary calcium, depending on their score, have Conclusion: Patients with coronary calcium, depending on their score, have an annual event rate 19-44x higher than patients without calciuman annual event rate 19-44x higher than patients without calcium.. Raggi, et al. Circulation 2000; 101:850-5.Raggi, et al. Circulation 2000; 101:850-5.

0.11

2.1

4.1

4.8

0

2

4

6

0 100-400 >400

Prospective Annualized Event Rate Prospective Annualized Event Rate in 632 asymptomatic pts over 32 in 632 asymptomatic pts over 32 months; 30 events-21 MI, 9 deathsmonths; 30 events-21 MI, 9 deaths

Perc

ent

Perc

ent

1-991-99Calcium ScoresCalcium Scores

Cardiovascular Events in Asymptomatic PatientsCardiovascular Events in Asymptomatic PatientsEBT vs. NCEP Risk FactorsEBT vs. NCEP Risk Factors

Conclusion: Patients in the highest quartile of calcium percentile have an Conclusion: Patients in the highest quartile of calcium percentile have an annualized event rate 22x higher than patients in the lowest quartile and 3x annualized event rate 22x higher than patients in the lowest quartile and 3x

higher than the highest quartile of all NCEP risk factors.higher than the highest quartile of all NCEP risk factors.Raggi, et al. Circulation 2000. ; 101:850-5Raggi, et al. Circulation 2000. ; 101:850-5

1 1

6.2

21.5

1

3.1 3.1

7

0

5

10

15

20

25

1st 2nd 3rd 4th

Odd

s Rat

ioO

dds R

atio

Calcium Percentile QuartilesCalcium Percentile QuartilesEBT EBT

All NCEP Risk FactorsAll NCEP Risk Factors

0.36 0.51 0.71 0.991.38

1.922.64

3.62

4.9

6.54

0

1

2

3

4

5

6

7

0 10 20 30 40 50 60 70 80 90

Percentile Rank for Baseline EBT Calcium ScorePercentile Rank for Baseline EBT Calcium Score

676 initially asymptomatic patients676 initially asymptomatic patients 3232++7 months f/u7 months f/u

Prediction of MI/SCD in Asymptomatic Patients by EBTPrediction of MI/SCD in Asymptomatic Patients by EBT

Raggi et al AHJ 2001;141:193-199Raggi et al AHJ 2001;141:193-199

%/yr%/yrAnnual Annual AbsoluteAbsolute Risk Risk

Prediction of Coronary Events with EBTPrediction of Coronary Events with EBT

14.3

19.7 20.2

3.34.5

2.93.7 3.52.6 2.94.8 5.8

4.44.0 3.0

0

5

10

15

20

25

CS >80 CS >160 CS >600

Calcium score Age Increased cholesterol Hypertension Diabetes

Odd

s Rat

ioO

dds R

atio

Arad et al, JACC 2000;36:1253-60Arad et al, JACC 2000;36:1253-60

1172 asymptomatic subjects, age 53 ± 11 years, 3.6 years follow-up: 36 events - 3 deaths, 15 MI, 21 revascularizations

Cardiovascular Events in Asymptomatic Patients: Cardiovascular Events in Asymptomatic Patients: Contribution of EBT Calcium Score IndependentContribution of EBT Calcium Score Independent

of Other Risk Factorsof Other Risk Factors

0

2

4

6

8

10

1 to 5 16 to 80 81 to 270 271+

Rel

ativ

e R

isk

Rel

ativ

e R

isk

(RR

)(R

R)

Total Calcium ScoreTotal Calcium Score

926 asymptomatic patients; mean age 54 926 asymptomatic patients; mean age 54 yryr2-4 year follow-up (mean 3.3 yrs);28 2-4 year follow-up (mean 3.3 yrs);28 events: MI-6;CVA-2; revascularization-events: MI-6;CVA-2; revascularization-2020

Adjusted for age, gender, hypertension, high cholesterol, past/current Adjusted for age, gender, hypertension, high cholesterol, past/current smoking, diabetessmoking, diabetes

Wong et al. AJC 2000;86:495-Wong et al. AJC 2000;86:495-88

5635 asymptomatic pts: 37+12 months follow up

4151 men (age 50+9) 1484 women (age 54+9)

224 events: death 21, MI 37, CABG 92, PCI 74

Kondos et al. Circ 2003:107:2571-6

EBT Coronary Artery Calcium and Cardiac EventsEBT Coronary Artery Calcium and Cardiac Events

RR Men WomenRR Men Women

CAC (>0) 10.5 2.6 CAC (>0) 10.5 2.6

Diabetes 1.98 -Diabetes 1.98 -

Smoking 1.4Smoking 1.4 - -

Events No EventsEvents No Events

CAC (>0) 95% 67% CAC (>0) 95% 67%

Score 483Score 483++686 101686 101++321 321

CORONARY CALCIFICATION, CORONARY DISEASE RISK CORONARY CALCIFICATION, CORONARY DISEASE RISK FACTORS, AND ATHEROSCLEROTIC CARDIOVASCULAR FACTORS, AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE EVENTS : THE ST. FRANCIS HEART STUDY DISEASE EVENTS : THE ST. FRANCIS HEART STUDY

Arad Y, Roth, R, Newstein, M, Guerci, AD. JACC 2003

METHODS• Prospective, population-based primary prevention study of 5585 men and women aged 50 to 70; no self referral

• Pts on statins or LDL >175 excluded

• 5585 subjects scanned with EBT; risk factors measured in 1817 • 4.3 years follow-up

• 122 (0.6%/year) with ASCVD event:

Nonfatal MI/coronary death 43

CABG/PTCA 62

Non-hemorrhagic stroke 5

Peripheral vascular surgery 12

0.12

0.7

2

2.4

3.3

0

0.5

1

1.5

2

2.5

3

3.5

0 > 0 > 100 > 200 > 600

Ann

ual E

vent

Rat

e %

Calcium Score

1 2.5

1216

32

0

5

10

15

20

25

30

35

0 Jan-99 100-199 200-599 >600

Rel

a ti v

e R

isk

1-990

0

Framingham 10 Year Risk

0

0.5

1

1.5

2

2.5

3

3.5

4

<10 % 10-20 % > 20 %

1st Tertile2nd Tertile3rd Tertile

Act

ual A

nnua

l Ris

k (%

)EBT Calcium Score and Framingham Risk ScoreEBT Calcium Score and Framingham Risk Score

~67% of Framingham Intermediate Risk were High or Low Risk by EBT

~45% of Framingham High Risk were Intermediate or Low Risk by EBT

Area under

ROC Curve P-value

Calcium score 0.81 + 0.03

<0.01<0.01

Framingham 0.71 + 0.03

EBT Calcium Score and Framingham Risk ScoreEBT Calcium Score and Framingham Risk Score

.80

.82

.84

.86

.88

.90

.92

.94

.96

.98

1.0

43210 5

Cum

ulat

ive

Surv

ival

Cum

ulat

ive

Surv

ival

Years of Follow-UpYears of Follow-Up

<10<10

10-10010-100101-400101-400

401-1000401-1000

>1000>1000

10,377 asymptomatic men and women10,377 asymptomatic men and womenf/u = 5.0f/u = 5.0++3.5 yrs.3.5 yrs.

Shaw et al, Radiology 2003

All Cause Mortality (NDR)in Pts Without Known CADAll Cause Mortality (NDR)in Pts Without Known CAD

unadjusted

All Cause Mortality in Pts Without Known CADAll Cause Mortality in Pts Without Known CAD

Shaw et al, Radiology 2003

CAC > Framingham, p<0.001

Prognostic Value of CAC: Screening in Subjects Prognostic Value of CAC: Screening in Subjects With and Without DiabetesWith and Without Diabetes

Raggi et al. JACC 2004;43:1663-9

Prognostic Value of CAC: Screening in Subjects With and Prognostic Value of CAC: Screening in Subjects With and Without DM Without DM

Raggi et al. JACC 2004;43:1663-9

High Coronary Artery Calcium Scores Pose an High Coronary Artery Calcium Scores Pose an

Extremely Elevated Risk for Hard EventsExtremely Elevated Risk for Hard Events

• 98 asymptomatic pts: CS >1000 (1328+287)

• 62 + 10 yrs• f/u 17 + 11 mos• 35 hard events: 12 deaths, 23 MI• Events vs no events: 1561

vs 1199 (p<.001)

Wayhs, et al. JACC 2002;39:225-300%

5%

10%

15%

20%

25%

AnnualizedEvent Rate

Calcium Score > 1000

Severely Abnl Nuc

EBT Calcium Scores and CRP in Predicting EventsEBT Calcium Scores and CRP in Predicting Events

7.5

3.4 1.6

4.42.8

10

2

4

6

8

High Medium LowLow

High

6.1

4.31.7

4.9

1.8 101234567

High Medium LowLow

High

Calcium ScoreCalcium Score Calcium ScoreCalcium Score

CRPCRP CRPCRP

RR: nonfatal MI, cor death RR: nonfatal MI, cor death PTCA, CABG, CVA (n=104)PTCA, CABG, CVA (n=104)

RR: nonfatal MI, cor death (n=50)RR: nonfatal MI, cor death (n=50)

Park, et al. Circ 2002;106:2073-Park, et al. Circ 2002;106:2073-77

967 asympt pts; age 67 967 asympt pts; age 67 ++ 8 yrs; 6.4+1.3 yr f/u 8 yrs; 6.4+1.3 yr f/uCalcium score: Low <3.7 Medium 3.7-142 High >142Calcium score: Low <3.7 Medium 3.7-142 High >142CRP: Low <75CRP: Low <75thth% High >75% High >75thth% (4.05mg/L)% (4.05mg/L)

No relation between calcium score and CRP: independent and complementary No relation between calcium score and CRP: independent and complementary

Coronary Artery Calcium in Acute Coronary Coronary Artery Calcium in Acute Coronary Syndromes: An EBT, Angiographic and IVUS StudySyndromes: An EBT, Angiographic and IVUS Study

• 118 consecutive pts: MI (101) or UA (17)

• 57+11 yrs • 114 ASHD: 110

moderate to severe disease by cath; 4 mild single plaques

• 4 non ASHD cause; none were EBT +

0%10%20%30%40%50%60%70%80%90%

100%

EBT +

EBT-

Schmermund, et al. Circulation 1997;96:1461-9

% of ASHD pts

Coronary Calcium in Young Patients with First MI: Coronary Calcium in Young Patients with First MI: Risk Factor Matched Analysis Risk Factor Matched Analysis

0102030405060708090

100MINo MI

Calcium Calcium PresentPresent >50>50thth%% >90>90thth%%

Pohle et al. Heart 2003;89:625-8

Perc

e nt

Perc

e nt

102 pts < 60; mean 102 pts < 60; mean 41.2 41.2 ++77 yrs yrsAge, sex and risk factor matched with healthy controlsAge, sex and risk factor matched with healthy controlsCulprit vessel calcified 90%Culprit vessel calcified 90%

mean score 529+903 mean score 119+213

“Coronary calcifications can be detected in the vast majority of young patients with their first unheralded myocardial infarction”

Coronary Artery Calcium in Acute Coronary SyndromesCoronary Artery Calcium in Acute Coronary Syndromes ConclusionsConclusions • EBT can identify the pool of patients from which ~95 %95 % of acute

MI’s or UA will emerge

• EBT does notdoes not identify the “vulnerable plaque”“vulnerable plaque”

• EBT doesdoes identify the “vulnerable patient”“vulnerable patient”

Schmermund, et al. Circulation 1997;96:1461-9

EBT Practice GuidelinesEBT Practice Guidelines

Society of Atherosclerosis ImagingSociety of Atherosclerosis Imaging

1. Males Males >>35 , females 35 , females >>45 without known heart45 without known heart disease with any of the following risk factors:disease with any of the following risk factors: family history of premature coronary disease hypertension

smoking (current or within last year) elevated LDL or reduced HDL by NCEP

2. Delay 10 yearsDelay 10 years if no risk factors

3. All All diabetics diabetics >> 35 35

Hecht, et al, AJC 2000;86:705-6

1988 Soviet Secretary Gorbachev and U.S. President Reagan sign the EBT Treaty, mandating EBT by SAI guidelines for American and Russian citizens

Improving Coronary Heart Disease Risk Assessment Improving Coronary Heart Disease Risk Assessment in Asymptomatic People: Role of Traditional Risk in Asymptomatic People: Role of Traditional Risk

Factors and Noninvasive Cardiovascular Tests (AHA Factors and Noninvasive Cardiovascular Tests (AHA Prevention V update)Prevention V update)

EBT recommended to improve prediction in intermediate risk pts: 6 –20 % Framingham 10 yr risk

40 % of adults40 % of adults

Greenland, Smith and Grundy, Circulation 2001;104:1863-7

NCEP ATP-III: Final ReportNCEP ATP-III: Final Report

• “Therefore, measurement of coronary calcium is an option for advanced risk assessment in appropriately selected persons. In persons with multiple risk factors, high coronary calcium scores (e.g., >75th percentile for age and sex) denotes advanced coronary atherosclerosis and provides a rationale for intensified LDL-lowering therapy. Moreover, measurement of coronary calcium is promising for older persons in whom the traditional risk factors lose some of their predictive power.”

AHA Guidelines for Cardiovascular Disease AHA Guidelines for Cardiovascular Disease Prevention in Women (2004)Prevention in Women (2004)

Implications of Recent Clinical Trials for theImplications of Recent Clinical Trials for theNCEP ATP-III GuidelinesNCEP ATP-III Guidelines

Risk LDL Goal Initiate TLC Consider Drug RxRisk LDL Goal Initiate TLC Consider Drug Rx

High: CVD <100 High: CVD <100 >>100 100 >>10010010 yr >20% 10 yr >20% Optimal <70 <100: consider drugOptimal <70 <100: consider drug

ModeratelyModerately <130 <130 >>130 130 >>130130highhigh: 2+RF : 2+RF 100-129: consider drug100-129: consider drug10yr 10-20%10yr 10-20%

ModerateModerate: <130 : <130 >>130 130 >>1601602+RF2+RF10 yr<10%10 yr<10%

Lower <160 Lower <160 >>160 160 >>1901900-1 RF 0-1 RF 160-190: consider drug160-190: consider drug

Grundy et al. Circulation 2004;110-227-239

Guidelines for Treatment in Asymptomatic, NCEP Classified Lower, Guidelines for Treatment in Asymptomatic, NCEP Classified Lower, Moderate and Moderately High Risk Patients Based upon CAC ScoreModerate and Moderately High Risk Patients Based upon CAC Score  CAC Score/CAC Score/ Framingham Risk Group Equivalent LDL Goal Drug TherapyFramingham Risk Group Equivalent LDL Goal Drug TherapyPercentile Percentile (mg/dl) (mg/dl)  00 Lower risk; 0-1 risk factors; Framingham <160 >190 risk assessment not required 160-189: drug optional  1-10 and1-10 and Moderate risk; 2+ risk factors <130 >160<<7575thth % % (<10% Framingham 10 year risk) 11-100 and11-100 and Moderately high risk; 2+ risk factors <130 >130 <<7575thth % % (10-20% Framingham 10 year risk) 100-129: consider drug  101-400 or101-400 or High risk; CAD risk equivalent <100 >100 >75>75thth % % (>20% Framingham 10 year risk) optional goal: <70 <100: consider drug   >400>400 Highest risk <100 >100 (>40% Framingham 10 year risk) optional goal: <70 <100: consider drug   consider ACE inhibitors and beta blockers

Hecht et al. JAMA: In Press

c. 400 BCE Hippocrates published regarding possible cases of angina, myocardial infarction, and sudden death; author of the Hippocratic Oath;Surgeon General of Greece

Oath,shmoath, just do the calcium score!)

Y O U R  T I M E / H E A L T H / P A G I N G  D R .  G U P T ABill Clinton's Big TestWhen he felt chest pains, he finally got an angiogram. Should you get one too?Monday, Sep. 20, 2004"I really think it probably saved my life," Bill Clinton told Larry King, speaking not about the bypass operation he had last week but about the test — an angiogram — that first showed that the arteries feeding blood to his heart were dangerously blocked. "If people have a family history there, and high cholesterol and high blood pressure," Clinton said, "they ought to consider the angiogram." Good advice? Yes and no. An angiogram is the gold standard of heart tests, and in Clinton's case it picked up a problem that all his previous stress tests and electrocardiograms had missed. But an angiogram is not something to be taken lightly. It involves injecting a dye directly into the blood vessels of your heart through a catheter that has been threaded into your chest from an artery in your groin. By taking X-ray images of the dye, doctors can get a pretty clear picture of where blood is flowing freely and where there are constrictions. But angiograms are not risk free. In about one case out of 1,000, according to Dr. Richard Stein, associate chairman of medicine at Beth Israel Medical Center in New York City, there are complications — including, in rare cases, strokes. For patients who have never had any symptoms (such as the chest pains and shortness of breath that Clinton experienced) and whose stress tests are normal, the risks outweigh the benefits, says Stein.

That's why there has been so much attention given lately to a noninvasive test called electron That's why there has been so much attention given lately to a noninvasive test called electron beam computed tomography (EBCT). It uses a burst of X rays to show how much calcium has beam computed tomography (EBCT). It uses a burst of X rays to show how much calcium has been deposited in the coronary arteries — a good measure of how much plaque has accumulated been deposited in the coronary arteries — a good measure of how much plaque has accumulated there. In a study published in the Journal of the American College of Cardiology, more than half there. In a study published in the Journal of the American College of Cardiology, more than half of 1,119 patients who passed their stress tests had high calcium scores in subsequent EBCTs, of 1,119 patients who passed their stress tests had high calcium scores in subsequent EBCTs, suggesting significant hardening of the arteries. suggesting significant hardening of the arteries. An EBCT is not the end of the story. If you get a high calcium count, you will still need an An EBCT is not the end of the story. If you get a high calcium count, you will still need an angiogram so your doctor can tell precisely where your arteries are blocked. angiogram so your doctor can tell precisely where your arteries are blocked. But EBCTs are But EBCTs are spotting a lot of hidden heart disease. Although some insurance companies are reluctant to pay spotting a lot of hidden heart disease. Although some insurance companies are reluctant to pay for this new test, its use is growing rapidly, and it may eventually become part of the standard for this new test, its use is growing rapidly, and it may eventually become part of the standard heart work-up. heart work-up. Sanjay Gupta is a neurosurgeon and CNN medical correspondent From the Sep. 20, 2004 issue of TIME magazine