1. Coronary Artery Calcium
Matthew Budoff, MD, FACC
Endowed Chair of Preventive Medicine
Professor of Medicine, UCLA Medical Center
Harbor-UCLA Medical Center
Torrance, CA

3. Cardiovascular Disease Deaths: United States 1979–1999
Women
Men
Deaths (in Thousands)
Cardiovascular disease deaths: United States 1979–1999
Since the release of the previous NCEP guidelines, instead of a marked fall in cardiovascular mortality in the United States the decline in cardiovascular mortality that predated the guidelines has slowed. In women, there has actually been an increase in incidence of cardiovascular mortality. Why is it, despite wide dissemination of guidelines that describe highly effective means by which cardiovascular risk can be substantially reduced, that cardiovascular mortality in the United States has not fallen substantially since 1988?
References:
American Heart Association Heart and Stroke Statistical Update. Dallas, Texas: American Heart Association, (available at
Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: Findings of the National Conference on Cardiovascular Disease Prevention. Circulation 2000;102:
NCEP I
NCEP II
NCEP III 79 81 83 85 87 89 91 93 95 97 99
Years
American Heart Association Heart and Stroke Statistical Update. Dallas, Texas: AHA, 2001.

4. Leading Causes of Death for All Males and Females United States: 1996 Mortality
600
505,930
500
453,297
400
Male
Female
Female
281,898
Deaths in Thousands
300
257,635
200
61,589
54,485
100
37,991
51,542
45,736
34,121
For decades, CHD was thought to be primarily a disease of middle-aged men. However, data now show that this disease is also the leading cause of death among women. In 1996, 505,930 women in the US died from CHD, which was almost twice that of cancer the second most common cause of mortality (257,635 deaths). These findings clearly illustrate the need for increased attention to the primary and secondary prevention of CHD in women, as well as in men.
Anderson RN et al. M Vital Stat Rep 1997;45(Suppl 2). A B C D E A B D E F
A Total CVD
B Cancer
C Accidents
D Chronic Obstructive
Pulmonary Disease
E Pneumonia/Influenza
F Diabetes Mellitus
Source: CDC/NCHS and the American Heart Association.

5. CHD - Breast Mortality

6. CONVENTIONAL (Population based) RISK FACTORS
Family History
Diabetes Mellitus
Elevated LDL Cholesterol
Low HDL Cholesterol
Tobacco Use
Hypertension
Obesity/Physical Inactivity

9. $150

10. The challenge in diagnosis of coronary heart disease
“The majority of people destined to die suddenly will not have a positive exercise test. The likely reason that they will die suddenly is that only a mild, non-flow -limiting coronary plaque will have been present before the sudden development of an occlusive thrombus.”
- Stephen Epstein
New England Medical Journal 1989 10

11. All Cause Mortality and CAC Scores:
Long Term Prognosis in 25,253 patients
Time to Follow-up (Years)
0 (n=11,044)
1-10 (n=3,567)
(n=5,032)
(n=2,616)
(n=561)
(n=955)
(n=514)
1,000+ (n=964)
2=1363, p< for variable overall and for each category subset.
Cumulative Survival
0.0
2.0
4.0
6.0
8.0
10.0
12.0
0.70
0.75
0.80
0.85
0.90
0.95
1.00
10.4 Fold
Increased Risk
Budoff, et al. JACC 2007; 49:

12. MESA Study – 6,814 Patients: 3.5 year follow-up
Nonfatal MI & CHD Death
14.13
(7.91,25.22)
10.26
(5.62,18.71)
At Tim’s suggestion and my preference I will be modifying the subsequent slides to look like this. That way I won’t be a total copycat.
4.47
(2.45,8.13)
Ref
Fully adjusted – Detrano et al– NEJM

13. NCEP ATP-III : Noninvasive Testing - 2001
“measurement of coronary calcium is an option for advanced risk assessment.
High coronary calcium scores (e.g., >75th percentile for age and sex) denotes advanced atherosclerosis and provides rationale for intensified LDL-lowering therapy.”

14. AHA – Circulation 2005
This recommendation - to measure atherosclerosis burden, in clinically selected intermediate CAD risk patients (eg, those with a 10% to 20% Framingham 10-year risk estimate) to refine clinical risk prediction and to select patients for altered targets for lipid-lowering therapies.

15. MEDICARE LCD- California
11. Quantitative evaluation of coronary calcium to be used as a triage tool for lipid-lowering therapy in patients with an intermediate to high Framingham risk score.
12. Quantitative evaluation of coronary calcium in patients with an equivocal stress imaging test or in cases in which discordance exists between stress imaging testing and clinical findings.

16. Blue Shield – February 2005

17. Blue Shield – February 2005

18. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk
After quantitative risk assessment:
assessment of 1 or more of the following— family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making.

19. PREVENTION GUIDELINES Goff 2013
“CAC is likely to be the most useful of the current approaches to improving risk assessment among individuals found to be at intermediate risk after formal risk assessment.”

21. MESA -CAC Distribution Across Statin Eligibility Groups*
*According to 2013 ACC/AHA Cholesterol Management Guidelines
10 year event rates in CAC 0:
0.5%/year in recommend statins (high intensity)
0.1%/year in consider statins (moderate intensity)
Nasir et al JACC 2015

22. CAC Distribution Across Statin Eligibility Groups*
*According to 2013 ACC/AHA Cholesterol Management Guidelines
10 year event rates in CAC 0:
0.5%/year in recommend statins (high intensity)
0.1%/year in consider statins (moderate intensity)
Nasir et al JACC 2015

23. CAC Distribution Across Statin Eligibility Groups*
*According to 2013 ACC/AHA Cholesterol Management Guidelines
CAC 0 reclassifies ~ ½ of candidates as not eligible for statins
10 year event rates in CAC 0:
0.5%/year in recommend statins (high intensity)
0.1%/year in consider statins (moderate intensity)
Nasir et al JACC 2015

24. EISNER Randomized Controlled Trial
2137 middle-aged + risk factors without CVD 45-79y without CAD/CVD followed 4 years
No Scan
Scan
Clinical evaluation
Questionnaire
Risk factor consultation
Clinical evaluation
Questionnaire
Risk factor consultation
CAC scan
Scan consultation
We do have, however, a RCT looking at intermediate outcomes. EISNER. In the EISNER trial, patients were randomized to no scan or scan. The only difference in the scan group is that patients received the CACS scan and a CACS report. No care was dictated to their providers.
Rozanski. Berman. Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research. JACC 2011;57:1622.

25. Does CAC scanning improve outcomes?
Parameters
No SCAN
CACS P
Change in LDL-C
-11 mg/dL
-29 mg/dL
<0.001
Change in SBP
-5 mm Hg
-9 mm Hg
Exercise
36%
47%
0.03
New Lipid Rx
19%
65%
New BP Rx
18%
46%
New ASA Rx 7%
21%
Lipid Adherence
80%
88%
0.04
Within the scan group, there was a favorable graded change… Whether this translates into improved outcomes we don’t know. Adherence to therapy significantly improved; however, look at the baseline.
Rozanski. Berman. EISNER. JACC 2011;57:1622. CACS 0 = 631. CACS>400 = 109.

26. EISNER Study – Costs Compared to No Scan Group
P<0.005 for both measures
Rozanski JACC 2011

27. What do Others Think?
In the broad middle, perhaps from 5% to 20% 10-year ASCVD risk, there is room for the patient-clinician discussion espoused by recent guidelines which could well be informed by judicious use of CAC screening.
Starting with a quantitative risk-based assessment, the patient and clinician first calculate the 10-year risk. If, after dicussion, they are uncertain whether the individual patient is likely to benefit from initiating a statin, obtaining CAC score would be reasonable.
Finding a CAC score of 0 in someone otherwise thought to be in a net benefit group is a powerful reason to consider withholding statin therapy.
Likewise, the presence of a high CAC score in an individual at only moderate predicted risk should be a powerful motivator to initiate and adhere to statin therapy.

28. Rotterdam – Annals 2012

29. WHAT CORONARY ARTERY CALCIFICATION MEANS
Atherosclerosis present in this vessel
Higher levels of coronary calcium correlate with higher risks
Zero calcification (none seen) suggests a very low probability of obstructive disease and less than 1% chance of heart attack and stroke over the next 5 years

30. Arad Y et al. J Am Coll Cardiol 2005: 46: 166-172.
ST FRANCIS RANDOMIZED TRIAL Randomized Double Blind Placebo Controlled Trial of Atorvastatin in the Prevention of Cardiovascular Events Among Individuals With Elevated CAC Score
Atorvastatin 20 mg (N=490) MI
Stroke
CVD Death
CABG/PTCA
No Prior CVD
Men, Women years
CAC >80%
of age-gender
Placebo (N=515)
Mean duration of treatment was 4.3 years.
Treatment with atorvastatin reduced clinical endpoints by 30% (6.9% vs. 9.9%), and MI/ Death by 44% (NNT 30)
Event rates were more significantly reduced in participants with baseline calcium score >400 (8.7% vs. 15.0%, p=0.046 [42% reduction]). (NNT 16)
Arad Y et al. J Am Coll Cardiol 2005: 46:

31. 2010 ACC/AHA Guideline for Screening in Asymptomatic Adults
Measurement of CAC is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (10% to 20% 10-year risk.
Measurement of CAC may be reasonable for cardiovascular risk assessment persons at low to intermediate risk (6% to 10% 10-year risk).
In asymptomatic adults with diabetes, 40 years of age and older, measurement of CAC is reasonable for cardiovascular risk assessment. * I
IIa
IIb
III * I
IIa
IIb
III * I
IIa
IIb
III

32. IMPROVED ADHERENCE

33. The best predictor of a life threatening illness is the early manifestation of a life threatening illness
Sir Geoffrey Rose
Cardiac Epidemiologist
Known for “The Rose Principle”

34. Contact Us
Phone: (310)