May 9, 2016 1Presented by: Michael J. Blaha
Michael J. Blaha MD MPH
Coronary Artery Calcium Scoring in Young and Low Risk Patients
Impact on Lipid-Lowering Pharmacotherapy Choices
Talk Outline
1. Rationale for clinical CVD risk prediction2. Weaknesses of existing CVD risk scores3. Coronary artery calcium (CAC), “disease
scores”, and “risk integration”4. CAC – not rare in young patients, prognostic!5. CAC and current prevention guidelines6. Clinical practice: CAC for guiding therapy
May 9, 2016 2
Rationale for Clinical CVD Risk Prediction
Part I
May 9, 2016 3
Level of Risk Factor
Prop
ortio
n of
Pop
ulat
ion
Optimal Borderline Elevated Very Elevated
Risk Factor Distribution
Level of Risk Factor
Rel
ativ
e R
isk
of C
VD
Elevated Very Elevated
Risk Factors and CVD Risk
High relative risk
Optimal Borderline
Level of Risk Factor
Tota
l CVD
Dea
ths
Elevated Very Elevated
Risk Factors and Total Number of Deaths
Total Number of Deaths
Optimal Borderline
Weaknesses of Present CVD Risk Scores
Part II
May 9, 2016 7
0 10 20 30 40 50 60 70 80 90
AGE
RISK
Traditional 10‐Year Risk Model
ATHEROSCLEROSIS
Risk Factor Exposure??
Outcomes??
9
Framingham Risk Score - MenAgeYears Pts20-34 -935-39 -440-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1275-79 13
CHD RiskPts 10-Yr
CHD Risk< 0 < 1%
0 1%1 1%2 1%3 1%4 1%5 2%6 2%7 3%8 4%9 5%
10 6%11 8%12 10%13 12%14 16%15 20%16 25%
> 17 > 30%
Systolic Blood Pressure
Untreated Treated<120 0 0120-129 0 1130-139 1 2140-159 1 2> 160 2 3
Total Cholesterol(mg/dL) 20-39 40-49 50-59 60-69 70-79<160 0 0 0 0 0160-199 4 3 2 1 0200-239 7 5 3 1 0240-279 9 6 4 2 1280 11 8 5 3 1
Cigarette SmokingNonsmoker 0 0 0 0 0Smoker 8 5 3 1 1
HDL-C(mg/dL) Pts> 60 -150-59 040-49 1< 40 2
HOW GOOD IS THE FRS AT PREDICTING MI? AKOSAH ET AL JACC 2003
222 patients with 1st acute MI, no prior CADmen <55 y/o (75%), women <65 (25%), no DM
75% did not qualify for pharmacotherapy
High Risk Intermediate Risk Low Risk
18%
12%
70%
New 2013 ASCVD Risk Calculator
Risk Factor Units Value
Acceptable range of values
Optimal values
Sex M or F M or FAge years 20-79Race AA or WH AA or WHTotal Cholesterol mg/dL 130-320 170HDL-Cholesterol mg/dL 20-100 50Systolic BP mm Hg 90-200 110Treatment for High BP Y or N Y or N NDiabetes Y or N Y or N NSmoker Y or N Y or N N
0.1
.2.3
.4.5
Pred
icte
d 10
-Yea
r Ris
k
40 50 60 70 80AGE
Framingham Risk Score ACC/AHA CVD Risk Score
Percent of U.S. Adults Who Would Be Eligible for Statin Therapy for Primary Prevention, According to Set of Guidelines and Age Group.
Pencina MJ et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1315665
Coronary Artery Calcium and Risk Integration
Part III
May 9, 2016 14
Continuum of Atherosclerosis Propagation Prior to a CHD Event
Genetics
Environment
Biomarkers
Risk Factors
Subclinical Atherosclerosis
Overt CAD
“Funnel”
0 10 20 30 40 50 60 70 80 90
AGE
RISK
Subclinical Disease Detection Model
Integrates Risk Exposure!!
Risk Factor vs. Disease Score
RISK FACTOR
• Measures increased risk for developing disease
• Separates risk elements• Usually mild risk
predictive value• Cancer analogy – high
hormone levels in breast cancer
DISEASE SCORE
• Measures the disease itself
• Integrates risk exposure• Usually a powerful
predictor of risk• Cancer analogy –
detection of suspicious nodule on mammography
~1 mSv
Relationship of Calcification to Coronary Atherosclerosis
May 9, 2016 19
20%
Rumberger, Circulation 1995
CAC Is Not Rare in Young Patients and is
Highly Prognostic! Part IV
May 9, 2016 20
CARDIA: CAC in Asymptomatic Individuals Age 33-45
21Rozanksi and Berman, JACCi 2013
CAC = 0 vs. Minimal CAC (1‐10)
• CAC=0 predicts excellent survival with 10‐year event rates of ~1%
• CAC 1‐10 patients had a 2‐3x increased risk for mortality vs. CAC=0
Blaha et al., JACC Cardiovasc Imaging, 2009.; Budoff et al., Am Heart J, 2009.
Tota-Maharaj, Blaha, et al. European Heart Journal. 2014.
0
10
20
30
40
<45 45-54 55-64 65-74 ≥75
0.7 0.6 1 2 2.8
1.6 1.2 3.7 5.913.8
6.83.2 5.5 9.6
20
27.6
7.5 11.719.9
37.9
Mortality/1000 person years
Age
CAC=0 CAC 1‐100 CAC 101‐400 CAC>400
Tota-Maharaj, Blaha, et al. European Heart Journal. 2014.
25
26
27
28
29
30
31
32
CAC and Prevention Guidelines
Part V
May 9, 2016 33
New ACC/AHA Guidelines –Primary Prevention
The Risk Discussion
Recommendations for Use of Newer Risk Markers After Quantitative Risk Assessment
If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following—family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making.†
I IIaIIb III
†Based on new evidence reviewed during ACC/AHA update of evidence.
37
38
Clinical Application –CAC for Guiding Lipid
PharmacotherapyPart VI
May 9, 2016 39
40
Continuum of ASCVD Risk
Primary Prevention
Advanced Subclinical
Atherosclerosis?
Secondary Prevention
Blaha MJ, AJC 2016
The Young “Lower Risk” Patient: Spectrum of Coronary Atherosclerosis
CAC = 0 CAC >0 Advanced CAC
Focus on lifestyle therapy and discuss statin
therapy
Recommend statin therapy
Recommend statin therapy and discuss
aggressive LDL‐C lowering to <70 mg/dL with statin
+ ezetimibe/PCSK9 inhibitor?
Blaha MJ, AJC 2016
SUMMARY AND TAKE HOME: CAC for Young Patients When Individualization of
Prevention Is Required!!
1. When Risk/Decision to Treat is Uncertain– Family History– Metabolic syndrome– Non-White, non-AA– Rheumatologic Diseases, etc– Borderline Lipids
2. Statin Reluctant Patient3. Statin Intolerant Patient4. Decisions for Non-Statin Add-on Therapy
May 9, 2016 43
MESA CHD Risk Score
May 9, 2016 44
The MESA CHD Risk Score
THANK YOU!!!!
May 9, 2016 46
Back-Up Slides
Part VII
May 9, 2016 47
HU x-factor(peak w/in lesion)
130-199 1
200-299 2
300-399 3
>400 4
Area = 15 mm2, Peak CT = 450Score = 15 x 4 = 60
Area = 8 mm2, Peak CT = 290Score = 8 x 2 = 16
Agatston Score = CAC area x maximal density factorCalculation of Agatston Score
Agatston AS et al. JACC 1990;15:827-32Images: Rumberger JA Mayo Clin Proc 1999;74:243-52
May 9, 2016 49
Warranty Period of CAC=0 in Years
15% (NNS~6) 20% (NNS=5) 25% (NNS=4)
Males Females Males Females Males Females
All 3.1 3.6 3.5 4.9 4.6 6.4
Low Risk 5.4 5.8 6.4 6.9 7.3 7.9
Intermediate Risk 3.2 3.3 4.3 4.3 4.8 6.0
High Risk 2.9 2.9 3.1 3.2 3.2 3.5
Warranty Period of CAC=0
MESA Study CAC Tools
May 9, 2016 50
MESA CAC Reference Values
May 9, 2016 51
52
53
54
0
1 to 99≥100
0
5
10
15
20
25
30
<1.801.80 to 2.57
2.58 to 3.34≥3.35
4.73.5
2.63.0
14.0
6.710.5
10.2
26.1 26.1 28.925.6
CA
CRat
e of
CVD
per
1,0
00 p
erso
n-ye
ars
CAC and LDL Cholesterol
Martin SS, et al. Circulation. 2013.
CAC vs CTA slide?
May 9, 2016 56
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