Coronary Artery Calcium Testing A Call For Univers
Coronary Artery Calcium Testing A Call For Univers
Review Article
A R T I C LE I N FO A B S T R A C T
Keywords: Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until
Cardiovascular disease (CVD) minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though
Atherosclerotic cardiovascular disease heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for
(ASCVD) asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying
Coronary artery calcium (CAC)
cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure
Atherosclerosis
Vulnerable patient
and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although
Computed tomography (CT) scan treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done
often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For
example, former President Clinton had passed his treadmill stress tests for several years during his presidential
annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our
limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is
available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured
non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with
colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC
testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC
coverage. Other states must step up and take actions.
⁎
Corresponding author.
E-mail address: [email protected] (M. Naghavi).
https://doi.org/10.1016/j.pmedr.2019.100879
Received 14 December 2018; Received in revised form 1 April 2019; Accepted 22 April 2019
Available online 02 May 2019
2211-3355/ © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
M. Naghavi, et al. Preventive Medicine Reports 15 (2019) 100879
Fig. 1. A schematic view of a dangerous coronary atherosclerotic plaque. This figure illustrates various molecular and cellular players in the development of a high-
risk atherosclerotic plaque inside the wall of a coronary artery. Permission obtained from Society for Heart Attack Prevention and Eradication.
total vulnerability to acute events. Early detection and treatment of and take actions similar to that taken in the state of Texas (HB1290,
such vulnerable patients have been the focus of research in preventive 2006).
cardiology for a long time; unfortunately not much progress has been
made..(Naghavi et al., 2003a; Naghavi et al., 2003b) Heart attack and 2. Cardiovascular disease map
stroke cause far more deaths in the US than all cancers combined.
(Benjamin et al., 2017) Despite this sobering fact, screening for The prevalence of CVD and its most common component, ASCVD, is
asymptomatic cancer is widely accepted, but screening for asympto- increasing across the United States and is expected to double by 2050.
matic ASCVD is not. Sadly, most patients who die from a heart attack (Casper et al., 2016; Heidenreich et al., 2011) In particular the Southern
have no symptoms until about an hour before they die. Since the 1980s, and Western regions of the U.S. have the highest prevalence and in-
standards of preventive cardiovascular testing have been limited to cidence (Fig. 2).
testing for high cholesterol, high blood pressure and other risk factors of In the West, Nevada has the highest rate of heart disease followed
atherosclerosis which were discovered in 1959 by the Framingham by California. In the Southeast, Mississippi has the highest rate of heart
Heart Study.(Dawber et al., 1959) Noninvasive detection of athero- disease followed by Oklahoma. Despite decades of public education
sclerosis itself by imaging was not possible then, but it is now, and costs about behavioral risk factors for CVD such as unhealthy diet, the
less than a mammography or colonoscopy. Despite a mountain of evi- American Heart Association reported that the prevalence of an ideal
dence suggesting that early detection and treatment of ASCVD can save diet score between 2002 and 2012 increased from only 0.7% to 1.5% in
lives and money, there is no initiative from healthcare policymakers to adults, meaning 98.5% of adults are still not following an ideal healthy
change the outdated status quo. Furthermore, there is no financial in- diet. The need for new strategies for prevention could not be clearer.
centive for the medical industry to invest in the primary prevention of (Writing Group, 2016)
ASCVD. Instead, every year the medical industry introduces expensive
new products (catheters, stents, surgical instruments, and pharmaceu-
3. What is wrong with the status quo?
tical drugs) for treatment of patients during and after a heart attack.
The latter is called secondary prevention, i.e., preventing recurrent
Measuring CVD risk factors such as age, smoking, hypertension,
heart attacks. Ironically, the financial incentive for prevention of the
diabetes, and dyslipidemia has been the status quo for estimating the
second heart attack is far greater than the financial incentive for pre-
risk of future ASCVD events. These risk factors are drawn from popu-
vention of the first heart attack.(Naghavi, 2010) In this paper we review
lation-based studies and do not translate to personal, specific risk in an
evidence that indicates that noninvasive detection of atherosclerosis is
individual. Many individuals with these risk factors will not experience
superior to the status quo, both for early detection and treatment of
an ASCVD event in their lifetime; conversely many patients who actu-
high-risk patients, and for reducing unnecessary therapy in low-risk
ally experience an ASCVD event do not have a high risk according to
individuals. We urge healthcare policymakers to examine the evidence
risk calculators. For example, in a study based on American Heart
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M. Naghavi, et al. Preventive Medicine Reports 15 (2019) 100879
Fig. 2. Heart disease death map: South and West have the highest rates. Age-adjusted heart disease death rates in ≥35 years old by county and quintile ranking (8).
Fig. 3. Of 136,905 patients hospitalized with CAC, 77% had normal LDL levels below 130 mg/dl. Red shows percentage of patients with a normal LDL cholesterol
level but experienced a heart disease event (11).
Association's Get with the Guidelines database, 77% of 136,000 patients who is going to have an ASCVD event. If Jim Fixx had an imaging study
who were diagnosed with coronary artery disease in the emergency for atherosclerosis, his outcome may have been much different.
room had normal LDL cholesterol levels (Fig. 3).(Sachdeva et al., 2009) Another problem with the status quo is that ASCVD kills and costs
Sir Winston Churchill was 91 when he died in his sleep. He was more than all cancers combined; nonetheless, investment in screening
overweight and a smoker. In contrast, the famous marathoner, Jim Fixx, for prevention and treatment of asymptomatic ASCVD is far less than
was 53 when he died of a heart attack. He was very fit and did not that of cancers. While two types of cancer screening (mammography for
smoke. Based on apparent risk factors, Fixx's heart attack risk was fairly breast cancer and colonoscopy for colorectal cancer) cost over $3000
low, and Churchill's was very high. Fixx is not the only marathon and are paid for by insurance companies, ASCVD screening is still
runner who was found to have atherosclerosis. A study was done ex- limited to less than $100 covered for measuring risk factors (Fig. 4).
amining 49 marathon runners who had participated in over 22 mara- Unfortunately, because of lack of insurance coverage, physicians today
thons.(Burgstahler et al., 2017) Atherosclerosis was diagnosed in 56% are not testing for atherosclerosis.
of the runners.(Casper et al., 2016) None of them smoked, had high In summary, the main problem with the status quo is that we as a
cholesterol, or any other risk factors that stood out. Therefore, the nation put more money to fix a heart attack during and after it happens
known ASCVD risk factors do not always tell the full story regarding rather than to prevent it in the first place. Furthermore, we use a
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M. Naghavi, et al. Preventive Medicine Reports 15 (2019) 100879
Fig. 4. Disparity between the burden of the disease (cardiovascular and cancer) versus the investment made in related preventive screening. Screening test coverage
for primary prevention of cardiovascular disease is < 10% of the coverage for screening for primary prevention of cancer.
Based on data from the National Center for Health and Statistics.
4. What are the advantages of the CAC score over the status quo?
The proof of the benefits of the CAC test lies in the hundreds of
scientific studies published so far. Budoff et al. followed over 25,000
asymptomatic patients over 12 years who were referred for coronary
artery calcium scoring. (Budoff et al., 2007) Out of 1000 patients who
had a CAC score of 0, over 99% lived. On the contrary, only 73% of
patients who had a high CAC score over 1000 survived.(Budoff et al.,
2007) Another study of > 85,000 patients showed that those with high
CAC score were 8 times more likely to experience a cardiac event than
those without. (Sarwar et al., 2009) Both studies show us the clear
correlation of a high CAC score to a high risk of an ASCVD event, and
low CAC score to low a risk. Perhaps the strongest evidence favoring
CAC over traditional risk factors came from MESA (Multi-Ethnic Study
of Atherosclerosis), a large NIH (National Institutes of Health) funded
study on ASCVD, that compared noninvasive tests to detect ASCVD in
6800 asymptomatic individuals and followed them for over 10 years.
CAC was the most powerful predictor of ASCVD risk.(Yeboah et al.,
2012) Data from 6 studies of 27,622 asymptomatic patients were
summarized in an ACCF/AHA clinical expert consensus document that
examined predictors of ASCVD events.(Greenland et al., 2007) The
11,815 subjects who had CAC scores of 0 had a low rate of events over
the subsequent 3 to 5 years (0.4%, based on 49 events). CAC scores
between 100 and 400 increased the risk to 4.3% (95% CI 3.5 to 5.2;
Fig. 5. United States Estimates and Overlap of CAC and Lung Scan Eligible p < 0.0001); and scores from 400 to 1000 had a 7.2% risk (95% CI 5.2
Patients to 9.9; p < 0.0001). Any score above 1000 indicated a risk of 10.8%
The number of eligible patients in the United States is estimated at 33 million events over 3–5 years (95% CI 4.2 to 27.7; p < 0.0001). No conven-
for CAC scanning (yellow) and 7 million for lung scanning in green. Excluding tional risk factor has shown such a predictive power. These studies
lung scan eligible patients who have established coronary disease (5.3%, un-
demonstrate that the relationships between CAC and outcomes are si-
published data from the I-ELCAP database) yields an overlap of 6.6 million lung
milar in men and women and different ethnic groups. Each of these
scan patients who would be expected to benefit from CAC scanning. Adapted
with permission from: (Hecht HS. Coronary artery calcium scanning: past, studies showed that the accuracy to predict coronary artery events is
present, and future. JACC Cardiovasc Imaging.) significantly higher with CAC than traditional risk factor-based risk
stratification alone. More recently Greenland et al. shed further light on
the clinical implications of CAC for ASCVD risk assessment, proposing
population-based statistical tool for risk assessment in an individual to
that CAC could be used to guide decisions about statin therapy when
decide who needs preventive intervention. We need to advance to
10-year ASCVD risk is 5–20%.(Greenland et al., 2018)
personalized risk assessment using noninvasive detection of athero-
It is noteworthy that a low-hanging fruit in the adoption of CAC can
sclerosis with a coronary artery calcium (CAC) score, the most studied
be found in over 20 million CT scans done annually in the US to screen
and evidence-based test that goes beyond conventional risk assessment.
for lung cancer (Fig. 5).
Patients can be informed about the presence of CAC on these scans.
Patients with higher levels of calcium in their coronary arteries in-
cidentally detected in these lung scans are more than twice as likely to
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M. Naghavi, et al. Preventive Medicine Reports 15 (2019) 100879
Fig. 6. In 2006 the SHAPE Task Force proposed the SHAPE Guideline(Naghavi et al., 2006) which is based on noninvasive detection of atherosclerosis using coronary
artery calcium scoring. The higher the burden of atherosclerosis the higher the risk, and the more intensive therapy needed. The “Intermediate Risk” category is the
focus of SHAPE Guideline and results in the majority of ASCVD events.
Table 1
Cost Effectiveness of SHAPE Guidelines. Cost effectiveness modeling predicts ~ $21.5 billion can be saved annually in the U.S. if SHAPE Guidelines are
adopted. (44).
Estimated impact of SHAPE Estimated change in cost: USA
die.(Hecht et al., 2014) While there needs to be more research done on and Framingham risk score (e.g., lower blood pressure and cholesterol
the subject of using CAC for mass screening to improve ASCVD out- levels). The CAC test is also expected to increase patient adherence to
comes, we could improve the status quo if CAC is adopted in a selected treatment. The phrase “seeing is believing” can apply to CAC. Seeing
population at intermediate risk. Furthermore, a zero CAC score comes calcium in their arteries helps patients visualize their risk and motivates
with a 5-year “warranty” of very low risk suggesting the patient may them to take action.(Maron, 2017)
not need treatment with a statin. (Min et al., 2010) Even if a patient has
high cholesterol, if their CAC score is zero they will be at low risk for 5. New guidelines based on CAC testing
ASCVD for the next 5 years. Some even argue that they have a low risk
of ASCVD for the next 15 years.(Valenti et al., 2015) These studies Over the past decade, a number of the coauthors of this paper have
convincingly show that a zero CAC score downgrades risk more than volunteered with the non-profit SHAPE (Society for Heart Attack
any other biomarker.(Blaha et al., 2016; Valenti et al., 2015) In the Prevention and Eradication) organization to create a new set of
EISNER trial (Early Identification of Subclinical Atherosclerosis by guidelines that utilizes noninvasive imaging of atherosclerosis, more
Noninvasive Imaging Research) investigators studied 2137 patients in specifically CAC testing.(Naghavi et al., 2006) Our main focus has been
primary prevention clinics.(Rozanski et al., 2011) Half underwent on identification of the vulnerable patient.(Naghavi et al., 2006) The
general clinical and risk factor evaluations, while the other half un- journey to find the vulnerable patients began almost two decades ago
derwent the same risk factor evaluations plus a coronary calcium scan. with the rise of interest in vulnerable plaques thanks to pioneering work
The half that received the scan showed a greater reduction in waist size by Davies et al. (Davies, 1990), Falk et al. (Falk, 1989), Willerson et al.
5
M. Naghavi, et al. Preventive Medicine Reports 15 (2019) 100879
(Casscells et al., 1996), and Fuster et al. (Fuster et al., 1985) After years
of research and discoveries it became obvious that for primary pre-
vention of ASCVD events we must broaden our scope from vulnerable
plaques to vulnerable patient.(Naghavi et al., 2003a; Naghavi et al.,
2003b)The SHAPE Guidelines were created as the first step on the path
toward identifying the vulnerable patient as an increasing mountain of
evidence emerged to indicate that asymptomatic individuals with the
highest level of CAC score had the highest risk and were most vulner-
able to ASCVD events..(Maron, 2017) More recently, we updated the
SHAPE flow-chart in light of the ACC/AHA recommendations (Goff Jr.
et al., 2013). See Fig. 6.
The SHAPE approach has been analyzed by healthcare economy
experts and found to be cost-effective if the CAC test is priced below
$200.(Shaw & Blankstein, 2010) Although the cost of a CAC test used to
be > $400, today it ranges from $100–$200.(Pletcher, 2016) This cost
is insignificant compared to the cost of stress electrocardiography,
stress echocardiography and nuclear stress tests which are often per-
formed on asymptomatic individuals and cost our healthcare system
millions of dollars. Cost-effectiveness analysis by Shaw et al. indicates
that the US healthcare system could save $21.5 billion dollars annually
if the SHAPE guidelines were adopted.(Shaw et al., 2018) (Table 1).
The 2018 update to the American College of Cardiology/American Fig. 7. Trend: Heart Disease, Texas vs U.S. This figure shows reported CVD* in
Texas vs. U.S. before and after passing Texas SHAPE Law HB1290. It is unclear
Heart Association guidelines for the management of cholesterol re-
whether this figure demonstrates a causal relationship or a random association.
commend CAC measurement when the decision about starting statin
(48)
therapy is uncertain from the patient or provider perspective. *Percentage of adults who reported being told by a health professional that they
According to the new guidelines, withholding or deferring statin in- have angina or coronary heart disease.
itiation is reasonable if CAC = 0 and the patient lacks other high-risk
features. If CAC score is ≥100, statin therapy should be started, in-
is now available; however, insurance companies do not cover it. By
cluding individuals whose risk estimate falls between 5% and 7.5%.
covering CAC score, many will be able to find out if they have coronary
(Grundy et al., 2018) This is a major change compared to previous
plaques. If so, they can be prompted to take preventive actions before a
guidelines and acknowledges the abundant evidence that individuals
heart attack occurs. This initiative has the potential to save lives and
with CAC ≥100 warrant more intensive preventive therapy and that
money. Texas has already passed HB1290 to mandate CAC coverage.
individuals with zero coronary calcium are very low risk. Lack of cov-
Other states and other countries can take this cause even further. They
erage for CAC testing deprives patients from personalized preventive
can set the goal to be the first to eradicate heart attacks. Although
care and results in undertreatment when therapy is indicated and un-
eradicating heart attacks requires a multipronged long-term approach,
necessary drug therapy when CAC = 0.
it is now well within our reach; and early detection of high-risk
asymptomatic individuals with CAC testing presents as a low-hanging
7. Texas Heart Attack Eradication Bill and similar initiatives
fruit. We must strive for a heart attack-free future for the next gen-
eration, the same way that the previous generation gifted us a polio-
In 2010, SHAPE helped Texas Representative Rene Oliveira to pass
and smallpox-free life.
the HB1290 bill, which requires reimbursement of up to $200 for a CAC
test in men ages 45–75, and women ages 55–75 who fall in the inter-
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