Coronary Artery Calcification:What It Means and How to Use It

Melvin E. Clouse, M.D.

A major teaching hospital of Harvard Medical School

Coronary Artery Calcification:• Wosika& Sosman-JAMA, 1934; 102:591-593• Snellan & Nauta-Fortschr Rontgenstahlen, 1937;

56:277-286• Habbe & Wright-Detection Coronary

Atherosclerosis. AJR, 1950; 63: 50-62• Blankenhorn & Stern-AJR, 1959; 81: 772-777• Electron Beam Computed Tomography: Imatron

(David King) • Agatston & Janowitz-Quantification of Coronary

Artery Calcium Using Ultrafast Computed Tomography. JACC 1990; 15: 827-32.

• Software Development Scoring/Reconstruction

Do We Need A New Test?

• Is there a problem?

• Will it be effective?

• Evaluate Current Trends

• Evaluate New Test

• Time line for acceptance

A major teaching hospital of Harvard Medical School

• 1.5 Million MIs per year and over 500,000 deaths per year.

• 40% of all deaths are in the US to CV disease. In 150,000 – 250,000 Americans the only symptom of CVD is a fatal heart attack

Conclusion: Desperate need for further early warning system

CORONARY ARTERY DISEASE

Magnitude of the Problem

P.T.

204 M<55, F <65 with MIs

• 60 % had LDL <131 mg/dl

• 41 % had LDL <100 mg/dl

• 38 % had LDL >130 mg/dl

• Only 25% would have qualified for Statins

using NCEP AATP III guidelines

Akosah et al, JACC 2003

Examples of Coronary Artery Scans

NO

CALCIFICATION

“zero score”

MODERATE

CALCIFICATION

SIGNIFICANT

CALCIFICATION

“high score”

Rx Recommendations/Ca++ ScoreSCORE 0

Risk Factor Modification onLo fat diet, Weight Reduction, No SmokingSerum LDL 100 mgm/dlFor Elevated LDL -- STATIN DrugsRe-exam 3 years

MODERATE SCORE – 25-50th %tileRisk Factor Modification – As AboveLDL 100 mgm/dlRe-exam 1 year

HI SCORE -- 75-90%tileTreadmill MIBI -- Same as above withStatins/LDL 100 mgm/dl

EBCT & NCEPIn Asymptomatic Women

304 without SX NCEP Hi Risk NCEP Lo Risk

EBCT+, EBCT-42% EBCT+ (score 73% tile) 58% EBCT-NCEP Hi Risk- 53.5% EBCT+: 37.7% EBCT -NCEP Lo Risk -46.5% EBCT+: 62.3% EBCT -

Lo Risk NECP (47% EBCT +) would not receive Rx Hi Risk NECP (37% EBCT -) would receive Rx

Hecht and Superko JACC 37:1506-1515 ( 1)

Using Ca++ as Reference Rx

58.6% Correctly Identified

<55 yrs. 65% correct>55 yrs. 52.2% correct

Hecht #2

Predictive Value CAC inPts. presenting with Chest Pain in ER

192 Pts (Mean Age 53 9 yrs.) followed 50 10 mo

•Excluded Pts with MI Dx

•Annualized Event Rate/yr.

0.6%/yr. for Score 0

13.9%/yr. for Scores >400 (P<0.001)

(22 of 38 pts with Scores >400 had cardiac event)Georgiou JACC 2001;38:105-10

NCEP ATP IIDietary Intervention

LDL-C >130 mg/dL > 2 Risk Factors

Drug RxLDL-C >160 mg/dL HDL-C < 35 mg/dL (also risk factor)

JAMA 269;3015-23, 1993

Total Cholesterol Education Program

ATP II ATP IIITotal Cholesterol100-200 100-199LDL 62-130 62-99HDL 35-77 40-77Triglycerides 30-200 30-149Lp(a) 30-140 <30

Framingham Heart StudyScore and Risk Prediction

Multivariable Statistical Model

Age Total Hypertension CholesterolSex HDLSmoking LDLDiabetes Triglycerides

Estimates coronary event risk in asymptomatic populations.

Note: 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.

Assessing CHD Risk in MenStep 1: Age

YearsPoints

20-34 -935-39 -440-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1275-79 13

Step 2: Total Cholesterol

TC Points at Points at Points at Points at Points at (mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79

<160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 3 1 0 240-279 9 6 4 2 1 280 11 8 5 3 1

HDL-C(mg/dL) Points

60 -1

50-59 0

40-49 1

<40 2

Step 3: HDL-Cholesterol

Systolic BP PointsPoints

(mm Hg) if Untreated if Treated

<120 0 0120-129 0 1130-139 1 2140-159 1 2160 2 3

Step 4: Systolic Blood Pressure

Step 5: Smoking Status

Points at Points at Points at Points at Points at

Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker 0 0 0 0 0Smoker 8 5 3 1 1

Age

Total cholesterol

HDL-cholesterol

Systolic blood pressure

Smoking status

Point total

Step 6: Adding Up the Points

Point Total 10-Year Risk Point Total 10-Year Risk

<0 <1% 11 8%0 1% 12 10%1 1% 13 12%2 1% 14 16%3 1% 15 20%4 1% 16 25%5 2% 17 30%6 2%7 3%8 4%9 5%

10 6%

Step 7: CHD Risk

ATP III Framingham Risk Scoring

Non-Invasive Testing Coronary Ca++

Risk-NCEP ATP III Population Recommend

Low 35% LifestyleHCE<10%

Intermediate 40% Noninvasive test Ca++,diet, statin

HCE<20%

High 25% IntensiveCHD, HTN, Diabetes intervention

(statins)FHS-Risk HCE/10yr >20%

Risk Assesment of Asymptomatic Patients

Coronary Ca++ studies must be able to predict the risk of future coronary events.

CAC/Predictor HCEPhysician/self referral

Arad et al 1996 Circulation 1173 pts

Arad et al 2000 JACC 1172 pts

Raggi & Callister 2000 Circulation 172/632 pts

Raggi & Callister 2001 AHJ 676/10,122 pts

Kondos 2003 Circulation 5635 pts

Shaw & Raggi 2003 Radiology 10,377pts

Wong et al 2000 AJC 926 pts

Predictive Value EBCT Coronary Arteries

19 mo follow-up 1173 pts.Mean age 53 +/- 11 yrs.18 subjects had 26 cv eventsCa++ thresholds

Score Sen % Spec % 100 89 77160 89 82600 50 95

Odds ratio range 20-34.4 (P<0.0009-0.00001) ARAD Circulation 1996

CAC Predictor HCEProspective Studies

Gerci, et al 2003 SFHS 5585 pts

South Bay Heart Watch:

Secci, et al 1997 Circulation 326 (462/461)Detrano, et al 1999 Circulation 1196 pts/2-3yr*Park, et al 2002 Circulation 967 pts / 6yrsGreenland 2004 JAMA 1312 pts /7yrs

(risk factor nor CAC event predictor, CAC no sig. incremental value,use not justified)

CAC/FRS

Non heterogeneous multi ethnic population 1029, 65+/- 7.8 years

CAC score >300 associated with higher risk coronary event than FRS alone.

Sig. Use when FRS is in 10-19% range for HCE in 10 years

Greenland et al. JAMA 2004;291:210-15

Predicting Coronary Death or Nonfatal Myocardial Infarction for Framingham Risk Scores (FRS)

The receiver operating characteristics curves illustrate FRS alone or plus coronary artery calcium score (CACS). Area under the curves are 0.63 for FRS alone, 0.68 for FRS plus CACS. P<.001 for the comparison between the 2 areas. Greenland et al, JAMA 2004; 291:210-215

17 y/o male

32 y/o female

0

20

40

60

80

100

0.5 mm threshold

0.3 mm threshold

13-19 20-29 30-39 40-49 >50

17% 21%

37%

66%

60%

75%

71%

85% 85%

91%

Pre

vale

nc

e o

f C

oro

na

ry

Ath

ero

scle

rosi

s (

%)

Tuzcu et al. Circulation 2001; 103:2705-2710

Atherosclerosis/CVD

• Long term, indolent, preventable disease• Accounts for 40 % of all deaths

– >2nd thru 7th leading causes of adult death combined

• 84.7 % who die are older than 65 years• 80% CHD mortality in individuals < 65 years of

age occurs during 1st attack • 57% men and 64% women who die suddenly

had no previous symptoms (150,000)• Cost – 386.4 billion (greater than 1/3 of our $1

trillion dollar health care economy)

CAC Summary• Follow CAC over time (RFM)

• Stable/Progression/Regression• Combine with FRS/NCEP ATP III• Before statin treatment• Cost benefit analysis algorithm initial

exam for cardiac work up• Chest pain patients-screen EW pts.

Rumberger et al, JACC 1999;33:453-62Raggi et al, Am J Cardiol 2000;85:283-28

Hect & Superko, JACC 2001;37:1 506-1 511Laudon et al, J Emergency Med 1999

Waters et al, Clin Investigation 1993

HOMELAND SECURITY

CAC Summary• Scanning technology validated

– Reproducible, variability – EBCT/MDCT

• Independent predictive value CAC for HCE• Only non-invasive method to demonstrate

total plaque burden• Plaque burden: most important predictor of

– hard coronary events / mortality

• Only non-invasive test to detect early CAD • Quantify disease• Institute measures to stop progression• Monitor disease progress

Development of Coronary Artery Plaque

Consistent with the “diffuse” nature of coronary artery disease, plaque development can be seen in various stages

in multiple areas of the coronary artery system.

EBT “positive” for coronary calcium

Atherosclerosis Timeline

FoamFoamCellsCells

FattyFattyStreakStreak

IntermediateIntermediateLesionLesion AtheromaAtheroma

FibrousFibrousPlaquePlaque

ComplicatedComplicatedLesion/RuptureLesion/Rupture

Endothelial Dysfunction

From first decade From third decade From fourth decade

Growth mainly by lipid accumulation Smooth muscleand collagen

Thrombosis,hematoma

Stary HC, et al. Circulation. 1995;92:1355-74. Artery wall often gets larger with increasing plaque-Glagov NEJM 1987