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

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. 2002 Heart and Stroke Statistical Update. Dallas, Texas: American Heart Association, 2001. (available at www.americanheart.org/statistics) 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;102:3137-3147. NCEP I NCEP II NCEP III 79 81 83 85 87 89 91 93 95 97 99 Years American Heart Association. 2002 Heart and Stroke Statistical Update. Dallas, Texas: AHA, 2001.

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.

CHD - Breast Mortality

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

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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

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) 11-100 (n=5,032) 101-299 (n=2,616) 300-399 (n=561) 400-699 (n=955) 700-999 (n=514) 1,000+ (n=964) 2=1363, p<0.0001 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: 1860-70

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 - 2008

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.”

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.

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.

Blue Shield – February 2005

Blue Shield – February 2005

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.

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.”

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

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

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

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.

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.

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

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.

Rotterdam – Annals 2012

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

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 50-70 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: 166-172.

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

IMPROVED ADHERENCE

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”

Contact Us Phone: (310) 222-4107 Email: Budoff@ucla.edu