Major Global Coron Art Calcium CAC Guidel SOTA Golub JACC 2023

JACC: CARDIOVASCULAR IMAGING VOL. 16, NO.
1, 2023
ª 2023 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
STATE-OF-THE-ART REVIEW
Major Global Coronary Artery

Calcium Guidelines
Ilana S. Golub, BS, Orly G. Termeie, BS, Stephanie Kristo, BS, Lucia P. Schroeder, BS, Suvasini Lakshmanan, MD,
Ahmed M. Shafter, MD, Luay Hussein, MD, Dhiran Verghese, MD, Jairo Aldana-Bitar, MD, Venkat S. Manubolu, MD,
Matthew J. Budoff, MD
ABSTRACT
This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic
cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing
similarities and differences in recommendations, this review identifies most notable common features for the application
of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as
follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of
Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia
for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European
Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the
2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1)
the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and
3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they
include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular
Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these
guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular
disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized
discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery
calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist.
However, international guidelines employ more similarities than differences from both a clinical and functional perspec-
tive. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to
correctly adjudicate personalized statin and aspirin therapy and further medical management.
(J Am Coll Cardiol Img 2023;16:98–117) © 2023 by the American College of Cardiology Foundation.
C ardiovascular disease (CVD) is a leading

cause of death worldwide, and accounts for
over 30% of annual global fatality.1 CVD is
also the leading cause of disease burden worldwide.
1990 to 18.6 million in 2019. Reducing coronary heart
disease mortality and morbidity necessitates a highly
sensitive risk assessment tool, followed by risk strati-
fication and treatment strategies. 2 This paper com-
Prevalent cases of total CVD nearly doubled from 271 pares guidelines from CV societies across the world
million in 1990 to 523 million in 2019, and the number to help encourage a homogeneous approach of CV
of CVD deaths steadily increased from 12.1 million in risk adjudication: coronary artery calcium (CAC)
From the Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.
Manuscript received April 11, 2022; revised manuscript received June 14, 2022, accepted June 22, 2022.
ISSN 1936-878X/$36.00 https://doi.org/10.1016/j.jcmg.2022.06.018

Descargado para Biblioteca Medica Hospital México (bibliomexico@gmail.com) en National Library of Health and Social Security de ClinicalKey.es por Elsevier en
enero 24, 2023. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.
JACC: CARDIOVASCULAR IMAGING, VOL. 16, NO. 1, 2023 Golub et al 99
JANUARY 2023:98–117 Major Global Coronary Artery Calcium Guidelines
screening. CAC is widely available, exhaustively stud- preventive therapy. Helping physicians un- ABBREVIATIONS
ied, and a highly specific marker of subclinical athero- derstand universal differences and similar- AND ACRONYMS
3
sclerosis. It is a vital arbitrator of atherosclerotic ities is key to empower the most fitting
ASCVD = atherosclerotic
cardiovascular disease (ASCVD) and accounts for choices in CVD prevention and management. cardiovascular disease
both stroke and coronary heart disease. 4 CAC testing
CLINICAL EVIDENCE AND STRENGTH CAC = coronary artery calcium
facilitates the up- or down-risking of asymptomatic
IN GUIDELINE RECOMMENDATIONS CAD = coronary artery disease
patients and provides a model for initiating or intensi-
CHD = coronary heart disease
fying preventive statin pharmacotherapies. Uniting
International CPGs are based on information CKD = chronic kidney disease
CAC risk stratification with cholesterol-modifying
from various sources. In preparing their CPG = Clinical Practice
treatment promotes a model for individualizing pri-
recommendations, the ACC/AHA included Guideline
mary ASCVD prevention and shared clinician-patient
only randomized controlled trials and their CV = cardiovascular
decision making.5
respective meta-analysis and systematic re- CVD = cardiovascular disease
Clinical Practice Guidelines (CPGs) are vital for
views. Studies of poor quality were rejec- DM = diabetes mellitus
structuring systematic and universally applicable
ted.9 Like the ACC/AHA, the NICE LDL-C = low-density
recommendations, to aid practitioner and patient
6
recommendations are determined from sys- lipoprotein cholesterol
decision making about appropriate health care.
tematic reviews and randomized controlled PCE = pooled cohort equations
Empowering a thorough understanding of accessible
trials. 12 The ESC/EAS and CCS, on the other SBP = systolic blood pressure
clinical evidence and international recommendation
hand, did not restrict the categories of
is key. This facilitates specialists’ ability to promote
studies. However, both European and Canadian
personalized decision making alongside patients and
agencies did apply rigorous analysis to published
to better an equitable physician-patient dialogue.7,8
recommendations and data. 10,11 Chinese guidelines
To simplify universal ASCVD risk assessment, it is
were determined from a platform of clinical and
incumbent on us to establish global solutions for
epidemiological studies completed within the Chi-
CPGs on CAC scoring. In this review paper, we
nese population. These studies were subsequently
therefore explore 7 guideline statements by respec-
integrated with international research and recom-
tive high-profile CV societies. From North America,
mendations.14,19 Each of these CPGs details the
we review the American College of Cardiology/
strength for every suggestion utilizing well-
American Heart Association (ACC/AHA) 9 and Cana-
established recommendation classes (ie, I, IIa, IIb,
dian Cardiovascular Society (CCS) 10 guidelines. From
and III) and evidence quality (ie, levels from
Europe, we review the European Society for Cardiol-
A to C).9-12,20,21
ogy/European Atherosclerosis Society (ESC/EAS)11
and the UK National Institute for Health and Care COMMON ASPECTS AND SCOPE OF GUIDELINES
Excellence (NICE) 12 guidelines. We also review Car-
diac Society of Australia and New Zealand (CSANZ) 13 INTERMEDIATE-RISK COHORT. With regard to risk
as well as the Chinese14 and Japanese Atherosclerosis stratification, most CPGs agree that CAC scoring is
Society (JAS) 15 guidelines. Last, we include state- vital to up- or down-classify intermediate risk
ments made by specialty societies including the Na- individuals. As indicated in Figure 1 and the Central
tional Lipid Association (NLA),16 Society of Illustration, the ACC/AHA recommend consideration
Cardiovascular Computed Tomography (SCCT), 17 and of risk enhancing factors, to guide clinician-patient
U.S. Preventive Services Task Force (USPSTF).18 risk discussion for intermediate risk adults (7.5%-
After describing major societies’ recommendations 20% 10-year ASCVD risk) and adults at borderline
and scope of guidelines, we evaluate strength of risk (5%-7.5% 10-year ASCVD risk). These include
recommendation in an evidence-level review. Next, familyhistory of premature ASCVD, persistently ele-
this paper assesses guideline recommendations’ vated low-density lipoprotein cholesterol (LDL-C)
comparison of risk scores in prediction of coronary $160 mg/dL or triglycerides $175 mg/dL, chronic
and CV deaths. We also review coronary calcium kidney disease (CKD), metabolic syndrome, condi-
guidelines within specific patient subgroups and tions specific to women (eg, preeclampsia, premature
ages. Furthermore, we examine international recom- menopause), inflammatory diseases (rheumatoid
mendations in utilizing CAC to guide statin, aspirin, arthritis, psoriasis, and HIV), high-risk race or
antihypertensive therapy, and CAC rescanning time ethnicity (eg, South Asian origin), and elevated high-
intervals. By summarizing the framework behind sensitivity C-reactive protein or lipoprotein(a) in
global guidelines of CAC in ASCVD risk assessment, selected individuals. If risk-based choices for pre-
this review paper helps advocate international syn- ventive interventions remain ambiguous, consider
thesis and applications in both the clinical setting and CAC as an adjudicator to upgrade risk (eg, young
100 Golub et al JACC: CARDIOVASCULAR IMAGING, VOL. 16, NO. 1, 2023
Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117
F I G U R E 1 The ACC/AHA Guidelines Recommend CAC for ASCVD Risk Stratification
LDL-C ≥190 mg/dL (≥4.9 mmol/L)

Primary Prevention: No risk assessment; High-intensity statin
Assess ASCVD Risk in Each Age Group (Class I)
Emphasize Adherence to Healthy Lifestyle
Diabetes mellitus and age 40-75 y
Moderate-intensity statin
(Class I)
Age 20-39 y Diabetes mellitus and age 40-75 y

Age 40-75 y and Risk assessment to consider high-intensity statin
Age 0-19 y Estimate lifetime risk
LDL-C ≥70-<190 mg/dL (Class IIa)
Lifestyle to prevent or reduce to encourage lifestyle to reduce
(≥1.8-<4.9 mmol/L)
ASCVD risk ASCVD risk
without diabetes mellitus
Diagnosis of Familial Consider statin if family history
10-year ASCVD risk percent Age >75 y
Hypercholesterolemia → statin premature ASCVD and LDL-C
begins risk discussion Clinical assessment, Risk discussion
≥160 mg/dL (≥4.1 mmol/L)
ASCVD Risk Enhancers:

• Family history of premature ASCVD
• Persistently elevated LDL-C ≥160 mg/ <5% 5% - <7.5% ≥7.5% - <20% ≥20%
dL (≥4.1 mmol/L) ”Low Risk” ”Borderline Risk” ”Intermediate Risk” ”High Risk”
• Chronic kidney disease
• Metabolic syndrome
• Conditions specific to women (e.g.,
preeclampsia, premature menopause)
• Inflammatory diseases (especially Risk discussion:
Risk discussion:
rheumatoid arthritis, psoriasis, HIV) Risk discussion: If risk estimate + risk
If risk enhancers present Risk discussion:
• Ethnicity (e.g., South Asian ancestry) Emphasize lifestyle enhancers favor statin,
then risk discussion Initiate statin to reduce
to reduce risk initiate moderate-
regarding moderate- LDL-C ≥50%
Lipid/Biomarkers: factors intensity statin to reduce
intensity statin therapy (Class I)
(Class I) LDL-C by 30% - 49%
• Persistently elevated triglycerides (Class IIb)
(Class I)
(≥175 mg/dL, (≥2.0 mmol/L))
In Selected Individuals if Measured:

• hs-CRP ≥2.0 mg/L If risk decision is uncertain:
• Lp (a) levels >50 mg/dL or >125 nmol/L Consider measuring CAC in selected adults:
• apoB ≥130 mg/dL CAC = zero (lowers risk; consider no statin, unless diabetes, family history of
• Ankle-brachial index (ABI) <0.9 premature CHD, or cigarette smoking are present)
CAC = 1-99 favors statin (especially after age 55)
CAC = 100+ and/or ≥75th percentile, initiate statin therapy
The figure elucidates the primary prevention guidelines for assessing atherosclerotic cardiovascular disease (ASCVD) risk. Notably, the blood cholesterol
guidelines discuss coronary artery calcium (CAC) as an arbitrator of statin use. CAC ¼ 0 suggests withholding statin therapy, while CAC ¼ 1 to 99 favors
statin for individuals >55 years of age. Last, CAC of over 100 requires initiation of statin therapy. Reprinted with permission from Grundy et al.67
ACC ¼ American College of Cardiology; AHA ¼ American Heart Association; apoB ¼ apolipoprotein B; CHD ¼ coronary heart disease; hs-CRP ¼ high-
sensitivity C-reactive protein; LDL-C ¼ low-density lipoprotein cholesterol; Lp(a) ¼ lipoprotein(a).
patients and women) or to de-risk (eg, elderly, dia- positive less often in this group than in those with
betes).9,22 The CCS likewise recommends CAC higher levels of ASCVD risk. Thus, CAC is recom-
screening for asymptomatic adults $40 years of age mended for low-risk patients only when risk-
years and with intermediate risk based on the Fra- enhancing factors are indicated. 9 Similarly, the CCS
mingham risk score (FRS) (10%-20%), for whom suggests that CAC screening is not indicated for most
treatment choices are unclear (Figures 2 and 3). 10 In the asymptomatic low-risk adults.10 However, the CCS
same regard, the CSANZ guidelines also recommend does indicate that CAC screening may be contem-
the CAC score for intermediate-risk individuals (10%- plated for a unique subset of low-risk individuals >40
20% 10-year ASCVD risk) who are asymptomatic, years of age with a family history of premature ASCVD
without known coronary artery disease (CAD), and 45 (men <55 years of age, women #65 years of age) and
to 75 years of age. 13,23 The UK NICE guidelines are genetic ASCVD indicators (elevated lipoprotein[a] or
similar to those already discussed but allow instead familial hypercholesterolemia). 10 The CSANZ simi-
for CAC scoring among all asymptomatic patients larly recommends that CAC can be examined for
with suggested electrocardiography changes for lower risk patients (absolute 10-year CV risk 6%-10%)
ischemia. 12 with the following circumstances: family history of
LOW-RISK COHORT. With respect to lower-risk in- premature CVD and diabetic patients 40 to 60 years of
dividuals, the ACC/AHA note that CAC score will be age.13,23 Likewise, the ESC/EAS guidelines employ CAC
C ENTR AL I LL U STRA T I O N Summary of Major Global CAC Guidelines
• CAC as an • CAC as a tool for • CAC scoring to up- • CAC as a risk

arbitrator of adjudicating
Major Worldwide Coronary classify or down- assessing tool,
statin use on
intermediate
statin allocation.
• For CAC scoring
Artery Calcium Guidelines classify their risk
(T1DM <35 yrs old,
risk
reclassification
risk. among all T2DM <50 yrs old), and therapy
asymptomatic with diabetes determinator.
patients with mellitus duration • Indicated in low
suggested ECG <10 years and risk with strong
changes for without other risk family history or
ischemia. factors. other concern
features.
• CAC as an • CAC as a
• High risk
arbitrator of prognostic tool in
reluctant to
statin use on intermediate- to
accept treatment,
intermediate high-risk • CAC as an arbitrator for
CAC is indicated.
risk. individuals. aspirin allocation.
• Local studies
suggested.
Common Indications Common Treatment Nonagreement

• Age: >40 y Threshold Points
+ • CAC = 0: downgrade risk, • CAC score for aspirin use
• Risk: Intermediate withhold statin • CAC score for
+ • CAC >100: Initiate / antihypertensive drugs
• Symptoms: Asymptomatic consider statin
population
Specialty Guidelines
• CAC = 0: No
• CAC = 0: No • Evidence is insufficient for
statin, repeat 3-7
statin. CAC addition to traditional
years.
• CAC >100: High CV risk assessment, in
• CAC >100: High
intensity statin + asymptomatic adults for
intensity statin +
ASA 81 mg. ASCVD prevention.
ASA 81 mg.
Golub IS, et al. J Am Coll Cardiol Img. 2023;16(1):98–117.
Among all discussed global coronary artery calcium (CAC) guidelines, common indications for CAC include the following: >40 years of age, intermediate level of risk,
and among an asymptomatic population. Common treatment thresholds indicate that for CAC ¼ 0, risk should be downgraded and statin withheld. For CAC >100,
statins should be considered or initiated. Nonagreement points between major guidelines surround the CAC score’s indication for aspirin use and antihypertensive
medications. ASA ¼ acetylsalicylic acid; ASCVD ¼ atherosclerotic cardiovascular disease; CV ¼ cardiovascular; ECG ¼ electrocardiography; T1DM ¼ type 1 diabetes
mellitus; T2DM ¼ type 2 diabetes mellitus.
score assessment for risk modification in asymptom- CAC ¼ 0 and no higher-risk conditions (ie, diabetes
atic individuals of low to moderate risk who would be mellitus [DM], family history of premature coronary
eligible for statin therapy. 11 For this cohort, ESC rec- heart disease [CHD], smoking), American guidelines
ommends CAC >100 for upward reclassification advise withholding statin therapy and reevaluating in
considering statin therapy. 11 CAC may also be explored 5 to 10 years.9 Similarly, the CCS reports that
in patients at low or moderate risk in whom the LDL-C abstaining from statin therapy for CAC ¼ 0 is
goal is not reached with lifestyle intervention alone. 11 reasonable, with reassessment during follow-up
Recently updated 2021 ESC Prevention Guidelines within 5 years for patients >40 years of age.10
restate that CAC may be considered to improve risk Similar to the ACC/AHA guidelines, the CCS does note
classification around treatment decision thresholds exceptions for intermediate-risk groups with high-
(Class IIb, Level of Evidence: B).24 risk features including smoking, diabetes, uncon-
CAC RISK THRESHOLDS. With regard to calcium trolled hypertension, and genetic dyslipidemias, and
burden adjudicating statin therapy, international individuals with prominent family history of prema-
CPGs also tend to agree among CAC score cohorts. The ture ASCVD events.10 For CAC subgroups 1 to 99, the
ACC/AHA advocates CAC as an appropriate stratifier ACC/AHA suggest that statin therapy is reasonable in
of statin use.9 For intermediate-risk individuals or those $55 years of age. 9 With CAC $100 or $75th
selected borderline-risk adults (classified within the percentile, American guidelines endorse statin treat-
context of the AHA/ACC guidelines as statin sug- ment for any age interval.9 Canadian recommenda-
gested and statin recommended, respectively) with tions employ CAC >100 as an indicator for
F I G U R E 2 The CCS Guidelines Recommend CAC for ASCVD Risk Stratification
PRIMARY PREVENTION†
Low-Risk* Intermediate Risk* High-Risk*

FRS <10% FRS 10-19.9% and FRS ≥20%
LDL-C ≥3.5 mmol/L or
Non-HDL-C ≥4.2 mmol/L or
apoB ≥1.05 g/L or
Men ≥50 yrs and women ≥60 yrs with one
additional risk factor: low HDL-C, IFG, high
waist circumference, smoker, or HTN or
with presence of other risk modifiers:
hs-CRP ≥2.0 mg/L, CAC >0 AU, family
history of premature CAD, Lp (a)
≥50 mg/dL (100 nmol/L)
Statin therapy not recommended for Discuss health behavior modifications

most low-risk individuals; exceptions
include: (a) LDL-C ≥5.0 mmol/L
(or apoB ≥1.45 g/L or non-HDL-C
≥5.8 mmol/L); or (b) FRS
is 5%-9.9% with LDL-C ≥3.5 mmol/L
(or non-HDL-C ≥4.2 mmol/L or apoB
≥1.05 g/L), particularly with other CV
risk modifiers (eg, FHx, Lp(a) ≥50 mg/dL INITIATE STATIN TREATMENT
[or ≥100 nmol/L] or CAC >0 AU) as the
proportional benefit from statin therapy
may be similar to other treated groups.
If LDL-C >2.0 mmol/L or apoB >0.8 g/L or

Health Behavior Modifications: NO
non-HDL-C >2.6 mmol/L on maximally tolerated statin dose
• Smoking cessation
• Diet: It is recommended all individuals YES YES
adopt a healthy dietary pattern.
• Exercise: It is recommended adults
accumulate at least 150 mins/week of
moderate-vigorous intensity aerobic
physical activity. Discuss add-on therapy with patient:
Evaluate reduction in CVD risk vs cost/access and side effects
ADD-ON
Monitor NO
• response to statin Rx
• response to add-on lipid-lowering Rx
• health behavior changes Ezetimibe as first-line
YES
(BAS as alternative)¶
The figure elucidates the primary prevention guidelines for assessing ASCVD risk and discusses CAC as an arbitrator of statin use. CAC screening is strongly indicated for
asymptomatic adults $40 years of age years and with intermediate risk (Framingham risk score [FRS] 10%-20%), for whom treatment choices are unclear. CAC
screening is not indicated for most asymptomatic, low-risk adults. For CAC >100, pharmacotherapy is reasonable regardless of FRS. However, for individuals with a CAC
of 1 to 99, the Canadian Cardiovascular Society (CCS) suggests that individual decision making is necessary because risk remains intermediate. Reprinted with
permission from Pearson et al.10 *Screening should be repeated every 5 years for men and women aged 40 to 75 years to reduce major cardiovascular events. A risk
assessment might also be completed whenever a patient’s expected risk status changes. †Calculate risk using the FRS. ¶Studies have evaluated the efficacy of BAS for
the prevention of ASCVD, but results have been inconclusive. AU ¼ arbitrary units; BAS ¼ bile acid sequestrant; CAD ¼ coronary artery disease; CV ¼ cardiovascular;
CVD ¼ cardiovascular disease; FHx ¼ family history; HDL-C ¼ high-density lipoprotein cholesterol; HTN ¼ hypertension; IFG ¼ impaired fasting glucose;
Rx ¼ prescription; other abbreviations as in Figure 1.
F I G U R E 3 Key Agreements Among Guidelines
Common Common Treatment Non-Agreement

Indications Threshold Points
• Age: >40 Y
+ • CAC = 0: • CAC score for
downgrade risk, Aspirin use.
• Risk: intermediate.
withhold statin.
+ • CAC score for
• CAC >100: antihypertensive
• Symptoms: Initiate / Consider statin medications.
asymptomatic
population.
This figure identifies common indications, common treatment thresholds, and nonagreement points among major global coronary artery
calcium (CAC) guidelines.
pharmacotherapy regardless of FRS.10 However, for factors (not limited to CAC score) to improve CVD
individuals with a CAC of 1 to 99, the CCS suggests assessment tools and primary prevention mea-
that individual decision making is necessary because sures. 19 However, current CPGs mainly focus on
10
risk remains intermediate. blood pressure and cholesterol levels, smoking sta-
The Australia and New Zealand guidelines, in tus, and age for risk stratification. 19 Therefore, the
contrast, utilize slightly different thresholds, as Chinese guidelines do not specifically discuss CAC
indicated in Figure 4 and the Central Illustration. The score subgroups for ASCVD risk adjudication. Chi-
CSANZ indicates CAC ¼ 0 for withholding statin nese CPGs suggest that enhancement factors (such
therapy, while CAC ¼ 1 to 100 favors lifestyle as family history of premature CVD; inadequate
improvement. CAC of 101 to 400 uniquely indicates regulation of cholesterol, blood pressure, and
treatment for individuals >75th percentile, and CAC glucose level; or significantly higher CAC score)
>400 requires initiation of statin therapy. Although should be further explored, along with accepted risk
patients with low CAC (1-100) have a 2-fold relative stratification. 19
risk compared with those without CAC, the CSANZ Japanese guidelines similarly report that CAC has
asserts that evidence for pharmacotherapy is weak.13 a high prognostic value for predicting CAD in inter-
However, in the MESA (Multi-Ethnic Study of mediate- to high-risk individuals (Central Illustration,
Atherosclerosis) study, event rates varied from 1.3% Table 1). However, CPGs state that this finding may
to 5.6% for CAC ¼ 0 and from 13.1% to 25.6% for CAC be swayed by Japan’s lower rate of CAD morbidity
>300. With other risk factors held constant, the MESA and mortality when compared with the Western
study estimated a 14% relative increment in ASCVD population’s.26 Therefore, Japanese guidelines sug-
risk for each doubling of CAC.25 CAC of 101 to 400, in gest that additional longitudinal studies are needed
our perspective, is a high-risk population that could to associate CAC score with CAD events within their
benefit from statin medication. The CSANZ instead population.26
recommends a healthy diet and lifestyle for main-
taining a low 10-year risk, except when increased-risk SPECIALTY GUIDELINES AND SOCIETIES. This re-
clinical factors are present.13 view focuses primarily on international guidelines.
NON-CAC ENDORSING. Chinese and Japanese Though this paper does not discuss them at length,
agencies differ from the aforementioned CPGs many specialty societies in addition to those afore-
(Central Illustration, Table 1). Chinese guidelines mentioned also endorse the CAC score. Here, we
appreciate the ACC/AHA guidelines that consider therefore introduce recommendations by the NLA,
nontraditional risk factors like CAC scoring for risk SCCT, AACE, Endocrine Society, and USPSTF and refer
assessment. In this regard, Chinese agencies plan to to them throughout the paper (Central Illustration,
apply both traditional and nontraditional risk Table 1).
also classifies specific CAC risk thresholds to adjudi-

T A B L E 1 Global CAC Guidelines Summary Table
cate pharmacotherapy (Central Illustration, Table 1).
Guideline Summary In adults 40 to 75 years of age with LDL-C 70 to
Country guidelines 189 mg/dL and without diabetes, active cigarette
United States CAC as an arbitrator of statin use on intermediate risk.
smoking, or a family history of premature ASCVD, the
Canada CAC as an arbitrator of statin use on intermediate risk.
NLA recommends deferring statin initiation when
United Kingdom CAC as a tool for adjudicating statin allocation.
For CAC scoring among all asymptomatic patients with suggested ECG CAC ¼ 0. In adults 76 to 80 years of age for whom
changes for ischemia. initiating statin therapy is uncertain, the NLA rec-
Europe CAC scoring to up-classify or down-classify their risk (type 1 DM <35
ommends CAC ¼ 0 as a factor favoring avoidance of
years of age, type 2 DM <50 years of age), with DM duration <10 y
and without other risk factors. statin therapy. 16 For adults with high CAC score,
Australia CAC as a risk-assessing tool, risk reclassification and therapy predominant left main coronary calcification, or
determinator.
Indicated in low risk with strong family history or other concern multivessel coronary involvement, the NLA does not
features. recommend stress testing or invasive coronary arte-
High risk reluctant to accept treatment, CAC is indicated.
riography if clinically relevant symptoms remain ab-
China CAC as an arbitrator for aspirin allocation.
sent. For patients with CAC $100, the NLA supports
Japan CAC as a prognostic tool in intermediate- to high-risk individuals.
Local studies suggested. initiation of statin therapy. Specifically for CAC $300,
Specialty guidelines and especially for CAC $1,000, the NLA recommends
NLA CAC ¼ 0: no statin, repeat 3-7 y. high-intensity statin therapy.16
CAC >100: high-intensity statin þ ASA 81 mg.
Like the NLA and many aforementioned major
SCCT CAC ¼ 0: no statin.
CAC >100: high-intensity statin þ ASA 81 mg. CPGs, the SCCT similarly indicates CAC scoring in
USPSTF Evidence is insufficient for CAC addition to traditional CV risk asymptomatic patients with unique clinical in-
assessment, in asymptomatic adults for ASCVD prevention.
dications (Figures 6 and 7, Central Illustration, Table 1).17
This table indicates key points for CAC screening, per each country and specialty guideline reviewed. Specifically, the SCCT endorses CAC screening for the
ASA ¼ acetylsalicylic acid; ASCVD ¼ atherosclerotic cardiovascular disease; CAC ¼ coronary artery calcium; following asymptomatic individuals without clinical
CV ¼ cardiovascular; DM ¼ diabetes mellitus; ECG ¼ electrocardiography; NLA ¼ National Lipid Association;
SCCT ¼ Society of Cardiovascular Computed Tomography; USPSTF ¼ U.S. Preventive Services Task Force. ASCVD: those 40 to 75 years of age and within the 5% to
20% 10-year ASCVD risk group, and those in the <5%
ASCVD risk group with a strong family history of pre-
One of the newest and most comprehensive mature CAD.17
guidelines, the NLA advocates CAC to guide pre- The American Association of Clinical Endocri-
ventive strategies for ASCVD risk reduction. The nology also emphasizes CAC measurement’s high
NLA explicitly categorizes CAC score as the best predictive value and utility in refining risk stratifica-
predictor of absolute 5- to 10-year ASCVD event risk tion to determine the need for more aggressive
(Figure 5, Central Illustration).16 Like most afore- treatment strategies (Grade B, Best Evidence Level
mentioned international guidelines, the NLA does 2). 27 The 2020 Endocrine Society CPGs similarly
not recommend CAC scoring for adults with clinical discuss CAC at length, specifically for lipid manage-
ASCVD but notes immense use in stratifying ment in patients with endocrine disorders. 28
borderline to intermediate- and low-risk adults. The For these adults at borderline or intermediate risk
NLA classifies borderline- to intermediate-risk (defined as 10-year ASCVD risk 5%-19.9%), the
adults as those 40 to 75 years of age, with LDL-C Endocrine Society recommends CAC to inform shared
70 to 189 mg/dL and a 10-year ASCVD of 5% to decision making regarding statin treatment and pre-
19.9%. For this cohort, the NLA suggests that CAC ventive intervention. 28
scoring may aid clinicians in determining the need In contrast, the USPSTF recommendations conflict
for and intensity of preventive therapies.16 The NLA entirely with those from the ACC, AHA, ESC, and
classifies low-risk adults as those 40 years of age or SCCT, among others, all of which advise consider-
older, with LDL-C 70 to 189 mg/dL and a 10-year ation of CAC testing in select populations. 18 Instead,
ASCVD risk of <5%. For this cohort, the NLA the 2018 USPSTF statement concludes that evidence
states that CAC scoring is reasonable for selective is insufficient for CAC addition to traditional CV risk
patients with a strong family history of premature assessment, in asymptomatic adults for ASCVD pre-
ASCVD, and may help adjudicate preventive therapy vention (Central Illustration, Table 1). The USPSTF
intensification or initiation. 16 asserts that the clinical meaning of any improve-
In tandem with American, Canadian, European, ments found with risk reclassification by CAC remain
UK, and Australian and New Zealand CPGs, the NLA largely unknown. 18
T A B L E 2 CAC in Guiding Statin Use
CAC Score
International
Guideline CAC ¼ 0 CAC 1-99 CAC >100 CAC >400
ACC/AHA Downgrade risk, Favors statin $55 Initiate statin therapy —

withhold statin years of age
ESC — — Upward reclassification and consider statin —
therapy
CSANZ Downgrade risk, Downgrade risk, CAC 101-400 and <75th Initiate statin
withhold statin withhold statin percentile ¼ consider statin treatment therapy
CAC score between 101 and 400 and >75th
percentile ¼ initiate statin therapy
CCS Downgrade risk, Personal decision Initiate statin therapy —
withhold statin making needed
NICE Downgrade risk, — þ Statin —
withhold statin
JAS — — — —
CSC — — — —
This table indicates statin pharmacotherapy recommendations per CAC score range, for each of the international guidelines reviewed.
ACC ¼ American College of Cardiology; AHA ¼ American Heart Association; CAC ¼ coronary artery calcium; CCS ¼ Canadian Cardiovascular Society; CSANZ ¼ Cardiac Society
of Australia and New Zealand; CSC ¼ Chinese Society of Cardiology; ESC ¼ European Society for Cardiology; JAS ¼ Japanese Atherosclerosis Society; NICE ¼ National Institute
for Health and Care Excellence.
CAC RESCANNING TIME INTERVALS LDL-C $70 mg/dL, the NLA recommends repeat CAC
scoring at 3 years to assess for accelerated progression
For the initial CAC ¼ 0 cohort, CPG guidelines differ (>20%-25% per year) or an increase to a CAC score
with regard to the timeline for repeating CAC >300.16
assessment. For low-risk individuals or those with Less specific than the NLA perhaps, the SCCT rec-
CAC ¼ 0, the ACC/AHA and CSANZ recommend that ommends repeat scanning for patients in whom CAC
CAC screening may be repeated in 5 to 10 years.4,13 progression would support intensification of preven-
The ESC guidelines recommend that for CAC ¼ 0, tive management. For these individuals, the SCCT
repeat screening should not be performed <5 years advocates repeat screening every 5 years when
from the initial scan.29 The CSANZ also recommends CAC ¼ 0 and every 3 to 5 years when CAC >0.17
that diabetic patients or those with CAC 101 to 400
should undergo repeat CAC at 3 years. 13 However, COMPARISON OF RISK SCORES IN
individuals with high CAC (>400) may not require PREDICTION OF CORONARY AND CV DEATHS
repeat CAC screening, seeing as these patients are
often symptomatic and already vigorously treated. 13 Although this review focuses on international CAC
For this high-risk subgroup, the CSANZ does indicate recommendations, elucidating worldwide guidelines
functional testing on an individualized basis. 13 for noncalcium risk adjudicators (such as risk scores)
Canadian guidelines, in contrast, do not recom- is also important for completion and comprehension.
mend repeat scans after CAC ¼ 0 unless personal risk As such, this paper briefly compares guideline rec-
factors are present, pharmacotherapy is deferred, or ommendations of risk scores for predicting coronary
follow-up is warranted. 10
The NICE guidelines also do and CV deaths.
not suggest a timeline for repeating CAC scans. International CPGs for pharmacotherapy decisions
The NLA recommends that the timing for repeat in ASCVD prevention rely heavily on CV risk assess-
CAC score depends on a patient’s baseline estimated ment and stratification. Guidelines for use of statins,
ASCVD risk, varying from 3 to 7 years. 16
Specifically, aspirin, and hypertension therapies are specifically
for CAC ¼ 0, the NLA advocates the following risk based, and these CVD prediction estimators
repeat scanning intervals: low-risk patients (<5% 10- empower synergistic decision making in clinician-
year risk) warrant 5 to 7 years, borderline- to patient discussions. 30 The ACC/AHA, ESC/EAS, CCS,
intermediate-risk patients (5%-19.9% 10-year risk) NICE, and Australian guidelines explicitly incorporate
warrant 3 to 5 years, and high-risk or diabetes pa- risk scores in CVD prediction and endorse CAC as a
tients warrant 3 years. 16
Specifically, for adults with well-established arbitrator.9,10,20,31 The current in-
CAC 1 to 99, the NLA advocates repeat CAC scoring in ternational promotion of personalized risk-based
3-5 years if the results might change treatment de- approach not only increases the yield of treatment
cisions. 16
For adults with CAC scores $100 and an in high-risk patients, but also reduces potential harm
F I G U R E 4 The CSANZ Guidelines Recommend CAC for ASCVD Risk Stratification
Asymptomatic
45 - 75 years old
(Diabetics >40 y)
Framingham Risk Score

http://cvdrisk.nhlbi.nih.gov/calculator.asp
Low risk <10% Intermediate risk High Risk >20%

No treatment 10-20% Treat
Strong family history,

Reluctant to accept
other concerning
treatment
features
CAC SCORE
101–400 >400
0 1-100
Consider treatment Treat:
No treatment, Improve diet and
(recommend if Aspirin
reassure lifestyle
>75th percentile) Statins
The figure elucidates an algorithm for suggested CAC scoring and assessing ASCVD risk. CAC ¼ 0 suggests withholding statin therapy, while
CAC ¼ 1 to 100 favors lifestyle improvement. CAC ¼ 101 to 400 indicates treatment for individuals >75th percentile, and CAC >400 requires
initiation of statin therapy. Reprinted with permission from Liew et al.13 CSANZ ¼ Cardiac Society of Australia and New Zealand; other
abbreviations as in Figure 1.
in low-risk patients that are less likely to encounter American, European, Canadian, United Kingdom,
absolute risk reduction. 32 and Australian and New Zealand guidelines all
The utilization of clinical risk estimation tools in recommend CAC as an absolute risk stratifier for
primary prevention has been widely examined and both cholesterol management and primary ASCVD
implemented in key guidelines worldwide.33 In 2013, prevention.9-13,32
the ACC/AHA developed an updated risk predictor Alongside short-term risk prediction via PCE, the
inclusive of CHD, CVD, and stroke events.34 Known 2019 ACC/AHA guidelines also recommend 30-year
as the pooled cohort equations (PCE), this 10-year risk evaluation by way of Lifetime Risk Estima-
ASCVD Risk Estimator was also recommended for tion.33,36 With the goal of assessing long-term impli-
initial ASCVD risk assessment in the later 2018 and cations of risk factor aggregate burden, the Lifetime
2019 guideline updates. 31 Dovetailing the PCE, the Risk Estimation tool is optimal for patients younger
2015 MESA study released a novel score for 10-year than 50 years of age with low short-term but elevated
CHD event prediction that united traditional risk lifetime risk.33
35
factors with CAC as a risk stratifier. CAC has been Like the ACC/AHA, European agencies similarly
widely indicated as the single best predictor of CVD promote absolute risk prediction tools alongside CAC
and CHD events, 32 and international guidelines have scoring. The 2019 European Guidelines specifically
adopted recommendations as such. Guidelines recommend the SCORE (Systemic COronary Risk
worldwide recognize the inherent imprecision of Evaluation) model for the prediction of 10-year risk of
multivariable CV event prediction tools and promote CV death, and the UK NICE utilizes the QRISK algo-
CAC as an arbitrator to improve discrimination, rithm to predict a composite outcome of CHD,
calibration, and net reclassification. 33 In ischemic stroke, or transient ischemic attack. 33,37 The
intermediate-risk patients in whom management is 2021 ESC guidelines have since upscaled the original
uncertain after risk predictors like the PCE, the SCORE to SCORE2, an improved algorithm now
F I G U R E 5 The NLA Guidelines Endorse CAC
Potential
Uses of CAC
Scoring
Family History Diabetes mellitus, Primary LDL-C Adults 76-80

Premature ASCVD no additional risk factors ≥190 mg/dL years of age
Adults < age 40 Adults age

Adults with DM age 40- Adults with
with major risk 10-Year risk <20%, No DM 76-80 when
75 for risk stratification primary LDL-C
factors or family doubt about
in absence of additional ≥190 mg/dL in
history of Adults age 40-75 statin
major risk factors or DM- absence of
premature CAD LDL-C 70-189 mg/dL
specific risk factors extreme LDL-C ↑ initiation
No diabetes or additional
10-year risk <20% major risk factors
± risk-enhancing factors,
CAC = 0 CAC >0 CAC ≥100 statin decision uncertain
CAC = 1-99
Lifestyle Lifestyle CAC = 0 High
Moderate
therapy and Moderate intensity
or high CAC = 0-10 CAC
and consider intensity statin and CAC = 0 CAC >0
intensity Favors >100
consider statin statin ASA 81 Favors high Favors high-
statin statin Favors
repeat mg daily* intensity intensity
CAC in avoidance statin
statin statin + add-
5-7 5-19.9% 10- on LDL-C
years year risk ↓therapy
<5% risk and CAC = 0

family No DM, no smoking, CAC ≥300
history of no family history CAC 100-299
CAC = 1-99
premature premature ASCVD
ASCVD history
Favors high-intensity statin and
if needed, add-on LDL-C↓
Favors Favors statin, therapy, ASA 81 mg daily* and
statin and ASA 81 mg consider BP goal <120 mm Hg
CAC = 0 CAC >0 Defer statin daily if not at
consider systolic
Lifestyle Lifestyle and and repeat high risk for
repeat in 3-
therapy consider in 3-5 years bleeding,
5 years
and statin and, if *If high bleeding risk is not present
consider needed drug
repeat therapy
CAC in for ↑BP
5-7
years
This figure shows a statement on CAC scoring to guide preventive strategies for ASCVD risk reduction and statin pharmacotherapy. Reprinted with permission from
Orringer et al.16 ASA ¼ acetylsalicylic acid; BP ¼ blood pressure; DM ¼ diabetes mellitus; LDL-C ¼ low-density lipoprotein cholesterol; NLA ¼ National Lipid Asso-
ciation; other abbreviations as in Figure 1.
estimating 10-year risk of combined fatal and ADVANCE (Action in Diabetes and Vascular Disease-
nonfatal CVD events.24 In contrast with SCORE’s use PreterAx and DiamicroN Controlled Evaluation) risk
of CVD mortality only, SCORE2 better estimates total score accounts for uniquely relevant variables such as
CVD burden with included nonfatal myocardial hemoglobin A1c, albuminuria, retinopathy, and atrial
infarction and stroke events.24 SCORE2 may be used fibrillation, in addition to traditional CV risk fac-
for populations without prior ASCVD 40 to 69 years of tors.33,39 The SMART (Second Manifestations of
age, while SCORE2-OP (older persons) may be applied Arterial Disease) risk score for patients with vascular
to those without ASCVD $70 years of age to estimate disease similarly includes unique variables (number
5- and 10-year risk of CVD (including myocardial of vascular disease locations, kidney function, high-
infarction and stroke). 24 sensitivity C-reactive protein, years since diagnosis)
Both American and European guidelines empower for increased specificity of CV risk stratification.33,38
a targeted, personalized approach to estimating CVD Last, the MAGGIC (Meta-Analysis Global Group in
risk. Unique to European preventive cardiology soci- Chronic Heart Failure) risk calculator is recom-
eties, however, is the push for CVD risk estimators mended uniquely for patients with heart failure.33
specific to special populations. Within an elderly Moreover, a key difference between the AHA/ACC
cohort, the JBS3 risk calculator and the elderly risk and ESC/EAS risk estimation tools (PCE and SCORE,
score account for competing nonvascular mortality respectively) are their endpoints. While the AHA/ACC
are recommended. 37,38 For patients with DM, the atherosclerotic risk adjudication utilizes the endpoint
a paramount risk factor in the predictive model of 10-

F I G U R E 6 The SCCT Guidelines Endorse CAC For 10-Year Risk Stratification
year CV disease risk. 19,43,44
CAC RECOMMENDATIONS IN SPECIAL

GROUPS OF PATIENTS
10-Year ASCVD 10-Year ASCVD 10-Year ASCVD
Risk <5% 5-20% >20%
Next, this review examines international CAC rec-
ommendations with regard to special groups of pa-
tients, including individuals with CKD and DM, and
gender differences.
Confirm low-risk CHRONIC KIDNEY DISEASE. In those with CKD, a

CAC not
status or up Reclassify up or significantly more pronounced, disseminated, and
recommended
classify risk down based on
except in special fast-progressing calcification of the vascular system
based on CAC CAC score
circumstances
score (including the coronary arteries) is often present.45
Coronary artery calcification develops early after the
onset of CKD and is closely associated with mineral
The figure indicates the role of CAC in guiding treatment for the 10-year ASCVD risk and bone disorders, which include but are not limited
categories. Reprinted with permission from Hecht et al.17 SCCT ¼ Society of Cardio-
to secondary hyperparathyroidism.45 Factors such as
vascular Computed Tomography; other abbreviations as in Figure 1.
inflammation and obesity, commonly seen in CKD,
lead to the acceleration of atherosclerotic plaques in
the arteries.45
of fatal and nonfatal myocardial infarction and Many of the CPGs discussed in this article therefore
stroke, the European SCORE CVD risk estimation rate CKD on a very high risk level and agree that
employs a hard endpoint of CV death. 33 initiating statin therapy is warranted. CAC scoring is a
The JAS Guidelines for Prevention of Atheroscle- valuable arbitrator, especially in cases in which in-
rotic Cardiovascular Diseases presented the NIPPON termediate risk patients may be up- or down-
DATA80 Risk Chart in 2012 to estimate absolute risk stratified for pharmacotherapy intervention.
of 10-year CVD mortality. 15
Risk factors include The CCS defines the usage of statins in CKD to
gender-specific tables, age, serum total cholesterol, include the following: 1) patients with an estimated
smoking, systolic blood pressure (SBP), and random glomerular filtration rate <60 mL/min/1.73 m 2; and
blood glucose. 15,40 Certain advantages were found in 2) those patients with preserved estimated glomer-
the NIPPON DATA80 Risk Chart, most notably: ular filtration rate in whom CKD is based on
random sampling across Japan, distribution of a increased urinary albumin-to-creatinine ratio
baseline survey conducted before statins were avail- ($3 mg/mmol) for at least 3 months¡ duration, all
able, and high suitability for observation of natural exempting patients on chronic dialysis. 10 The CSANZ
disease course.15 Concerns with the NIPPON DATA80 adds that CKD patients classified as extremely high
Risk Chart include its lack of LDL-C or high-density risk may be exempted from CAC screening because it
lipoprotein cholesterol consideration and its is unlikely to alter the recommended management of
employment of death as predicted outcome in place the disease.13 The ESC/EAS adds that active man-
of CAD incidence. Also problematic is NIPPON’s 1980 agement instead of risk assessment by CAC is of
baseline year and its higher estimation of mortality more vital importance for those with CKD.11 The
than actualized when applied to more recent ACC/AHA note that CKD is already a risk enhancer. If
populations.15,41 there is still uncertainty regarding risk estimate,
The Chinese Society of Cardiology notes that American guidelines allow for reclassifying up or
widely used prediction models (ie, European SCORE down with CAC.9
model and American pooled cohort studies equa- DIABETES MELLITUS. Another special group of pa-
tions) are based on European and American popula- tients are those with DM, a cohort thoroughly dis-
tion data and thus cannot be fully extrapolated to cussed by the CPGs included in this paper.
Chinese cohorts.19,42 Instead, Chinese cardiology so- Individuals with diabetes present with a risk for CV
cieties employ the 2016 Chinese Guidelines for the events comparable to those for patients with an
Management of Dyslipidemia in Adults for 10-year actual ASCVD history. Thus, the presence of any CAC
ASCVD risk assessment. These recommendations in individuals with DM equates with a higher risk of
are rooted in long-term follow-up data from the all-cause mortality, and CAC scoring becomes of vital
Multi-provincial Cohort Study, and suggest that age is importance as a risk stratifier.46
F I G U R E 7 The SCCT Guidelines Endorse CAC in the 5% to 20% ASCVD Risk Group
Score Risk Treatment Recommendation
0 very low statin not recommendeda
moderate intensity statin if <75th%;

1-99 mildly Increased
moderate to high intensity if >75th%
100-299 moderately increased moderate to high intensity statin + ASA 81 mg
>300 moderate to severely increased high intensity statin + ASA 81 mg
This figure endorses CAC score–determined risk classifications and treatment recommendations in the 5% to 20% ASCVD risk group.
a
Excluding familial hypercholesterolemia. Reprinted with permission from Hecht et al.17 Abbreviations as in Figures 1, 5, and 6.
The ESC/EAS guidelines indicate that young pa- initiation of statin therapy.13 The ESC/EAS indicate
tients (type 1 DM <35 years of age, type 2 DM <50 that patients with DM and target organ damage, DM
years of age), with DM duration <10 years and >10 years, or early onset of type 1 DM of long duration
without other risk factors, are considered at low- (>20 years) should receive immediate attention that
moderate risk for ASCVD. 11 Within this patient does not stipulate preventive calcium scoring. 11 In
segment, European guidelines suggest that in- instances of longstanding or more severe forms of
dividuals may benefit from CAC scoring to up- or diabetes, immediate treatment is deemed the most
down-classify their level of risk standing.11 The necessary course of action, and CAC remains a vital
CSANZ describes parallel recommendations: lower- adjudicator for up- or down-risking intermediate-
risk patients between 40 and 60 years of age with group patients.
DM may similarly benefit from CAC scoring.13 The CCS The NLA similarly offers detailed recommenda-
echoes the ACC/AHA and denotes that intermediate tions for CAC in patients with DM, stratified uniquely
risk factors, including impaired fasting glucose (in by age, risk severity, and lipid thresholds. The NLA’s
men at or older than 50 years of age and women at or guidelines are highly specific. For adults 40 to 75
older than 60 years of age) along with a risk modifier years of age with DM and an LCL-C 70 to 189 mg/dL,
of CAC >0, favor the use of statins. 10 The ACC/AHA the NLA indicates a moderate- or high-intensity statin
further elaborate that clinicians should not down- regardless of CAC score.16 For adults 40 to 75 years of
classify risk in diabetic patients who have a CAC of age with DM who are preparing to initiate statin
zero due to the potential presence of noncalcified therapy, a CAC >100 helps adjudicate high-intensity
plaques.9 Consensus among international guidelines statin use. 16 For adults 30 to 39 years of age with
supports that, in patients with DM that are deter- long-standing DM (type 1 diabetes of >20 years or
mined to be low-to-moderate risk, CAC is importantly type 2 diabetes of >10 years) and risk factors or
indicated to further stratify atherosclerotic risk microangiopathy, the NLA advocates CAC scoring to
assessment. facilitate ASCVD risk stratification and shared deci-
In more severe and high-risk DM patients, howev- sion making with regard to statin treatment. Last, in
er, the CPGs described previously trend toward im- adults older than 75 years with type 2 diabetes (for
mediate statin therapy as opposed to preventive CAC whom whether to employ a statin for primary pre-
score assessment. The CCS recommends that patients vention remains uncertain), the NLA recommends
with DM over 40 years of age (or over 30 years of age CAC scoring to aid statin adjudication.16
with at least 15 years’ duration) should initiate statin GENDER DIFFERENCES. In the last few decades, sig-
therapy immediately.10 Similarly, the CSANZ defines nificant sex-specific differences in the epidemiology of
this group as diabetics over 60 years of age or di- CVD have also been studied and established.47,48
abetics with albuminuria, and also echoed the Although they develop CVD approximately 10 years
risk. The ACC/AHA, CSANZ, ESC/EAS, and CCS

F I G U R E 8 The ACC/AHA Recommendations for Aspirin Use
guidelines all promote CAC scoring to guide phar-
macotherapy if patients are between 40 and 75 years
COR LOE Recommendations
of age, if patients are asymptomatic, or if risk is
1. Low-dose aspirin (75-100 mg orally daily) calculated to be intermediate or uncertain.4 CAC’s
might be considered for the primary immense benefit comes from its ability to reclassify
prevention of ASCVD among select adults
IIb A 40 to 70 years of age who are at higher this intermediate-risk patient population into either a
ASCVD risk but not at increased bleeding lower- or higher-risk pool. 4 The NICE guidelines are
risk.S4.6-1–S4.6-8
similar to those discussed for this age group but allow
instead for CAC scoring among all asymptomatic pa-
2. Low-dose aspirin (75-100 mg orally daily) tients with suggested electrocardiography changes
should not be administered on a routine
III: Harm B-R basis for the primary prevention of ASCVD for ischemia.12
among adults >70 years of age.S4.6-9 YOUNGER PATIENT POPULATION. Guidelines differ,
however, when discussing CAC scoring among a
3. Low-dose aspirin (75-100 mg orally daily) younger patient population. For low-risk individuals
should not be administered for the primary
prevention of ASCVD among adults of under 45 years of age, the ACC/AHA and CCS use CAC
III: Harm C-LD
any age who are at increased risk of scoring more sparingly. They reserve this screening
bleeding.S4.6-10
instead for younger patients with increased risk fac-
tors. For this subgroup, the ACC/AHA recommends
that ASCVD risk factors be evaluated every 4 to 6
The figure elucidates American recommendations for aspirin use. Notably, aspirin phar- years and that CAC scoring be performed if there are
macotherapy is only recommended for adults 40 to 70 years of age, with high ASCVD
risk factors including history of hyperglycemia,
risk but no increased bleeding risk. Referenced studies that support recommendations are
summarized in Online Data Supplements 17 and 18. Reprinted with permission from
hyperlipidemia, hypertension, or smoking. 9 CCS
Cainzos-Achirica et al. 57
COR ¼ class of recommendation; LOE ¼ level of evidence; guidelines are similar for this age group. They too
other abbreviations as in Figure 1. consider CAC scoring in individuals with a strong
family history of premature CVD events, smoking
history, diabetes, hypertension, or genetic dyslipi-
later in life than men, women have a 2 increased risk
demias.10 These guidelines each follow results and
of CV death as compared with men with the same CAC
recommendations from the CARDIA (Coronary Artery
burden.47 Atherosclerotic imaging risk markers are
Risk Development in Young Adults) trial. The CARDIA
similarly correlated with higher risk of CHD events in
trial indicated that CAC >0 is common among in-
women than men.48,49 The CSANZ emphasizes that
dividuals 32 to 46 years of age with risk factors and
FRS frequently underestimates women’s risk, even in
warrants follow-up.52 Unlike American and Canadian
the presence of CAC >100 or CAC >75th percentile. 13,50
recommendations, The CSANZ guidelines suggest
In fact, a MESA study of FRS-allocated low-risk women
initiating the assessment of CV risk via CAC score at
found 6% with CAC >100 and 4% with CAC >300.51
45 years of age. 23,53
Citing that most women under 60 years of age are
The ESC/EAS guidelines also utilize age stratifica-
stratified as low risk by the FRS, the CSANZ guidelines
tion for predicting ASCVD risk. In fact, ESC/EAS prefer
therefore suggest CAC for those with 6% to 10% 10-
the CV risk age, with accounts for individual risk
year risk.13
factors.11 Still, the ESC/EAS has not yet endorsed the
Although studies indicate that CAC screening is
use of CAC scoring in younger or lower-risk in-
equally accurate in allocating risk in women and men,
dividuals due to lower prognostic yield, associated
data on gender-informed CAC parameters for pre-
costs, and radiation hazards.11 The NICE guidelines
dicting ASCVD risk are scarce.48,49 To this point,
employ CAC scoring as a “gatekeeper” for younger
major international CPGs have yet to include detailed
patients presenting with angina and intermediate
recommendations for gender-based CAC stratifica-
CVD risk.12,54 The NICE promotes further investiga-
tion. Additional data on long-term CV risk among
tion and imaging for all symptomatic individuals, not
women versus men based on CAC measures are
limited to computed tomography angiography.12,54
imperative to focus preventive strategies of care.
The NLA similarly advocates CAC scoring in
CAC AMONG YOUNGER AND OLDER AGE GROUPS adults <40 years of age selectively, only for patients
with multiple major ASCVD risk factors or with a
Recommendations stratified by age are strongly family history of premature ASCVD. 16 For these
consistent when evaluating a 40- to 75-year-old pa- selected adults, the NLA recommends that CAC
tient population classified with intermediate ASCVD >0 favors lifestyle therapy up-regulation and risk
stratifying to more intensive CVD-preventive individualized CV care, providing clinicians the tools
therapies.16 to alter statin therapy via personalized CAC scores.
OLDER PATIENT POPULATION. For individuals >75 According to CAC score and associated risk group,
years of age, guidelines worldwide acknowledge the patients can be subsequently up- or down-risked and
utility of CAC in reclassifying CV risk and predicting statin therapy deferred or initiated. 4
CV mortality.40 Yet, CPGs do employ slight variations Most CPGs agree that a reported CAC score of
in their overall approach to CAC screening within this 0 (with all other ASCVD risk factors remaining low) is
population. reason to downgrade risk and withhold statin ther-
The ACC/AHA utilize CAC scores to assist risk apy. The CCS makes an exception and adds that statin
reclassification among this older patient de- therapy should be considered in patients with zero
mographic. Identifying atherosclerotic plaque subse- CAC, if positive for the following risk factors: history
quently allows for the downgrading or upgrading of of cigarette smoking, diabetes, poorly controlled hy-
risk and the deferral or initiation of pharmacotherapy, pertension, genetic dyslipidemias such as familial
respectively. More specifically, the ACC/AHA guide- hypercholesterolemia or elevated lipoprotein(a), or
lines state that for adults 76 to 80 years of age with an strong family history of premature ASCVD events.10
LDL-C level of 70 to 189 mg/dL, CAC of 0 warrants the Only the ESC/EAS guidelines differ slightly; European
deferral of statin therapy.9 The NLA similarly specifies agencies do not outline a recommendation for
an age range of 76 or 80 years, in which CAC scoring downgrading risk and deferring statin therapy within
may be selectively used to reclassify ASCVD risk and a zero CAC demographic.56
16
facilitate statin treatment decisions. For the CAC 1 to 99 subgroup, the ACC/AHA justify
The CCS guidelines, in contrast, use 40 years of age initiating statin therapy in patients $55 years of age. 9
as a point of reference. The Canadian recommenda- Canadian guidelines recommend that this CAC range
tions suggest that individuals $40 years of age years allows for personalized decision making, as CV risk
who are asymptomatic and at intermediate risk remains intermediate. If therapy is withheld, the CCS
should receive CAC scoring. 10 However, individuals advises close follow-up.10 The CSANZ advocates
$40 years of age years who are high risk, asymp- against aspirin and statins for this CAC ¼ 1 to 99
tomatic and low risk, or on statin therapy do not subgroup.13,55 Of note, the ESC/EAS do not explicitly
necessarily require CAC screening. Of course, a ge- describe this CAC score range.56
netic cause or family history of premature ASCVD is The CAC >100 cohort is generally consistent among
an exception.10 CPGs for adjudicating statin use. The ACC/AHA, CCS,
The CSANZ guidelines recommend that, before and NICE all justify statin therapy with CAC above
CAC screening is performed for those older than 75 100. The CSANZ, in contrast, considers 101 to 400
years of age, CVD risk should first be calculated via and <75th percentile as only intermediate risk. 13
the National Vascular Disease Prevention Alliance risk However, for CAC scores between 101 and 400 and
assessment. However, if personal risk factors are >75th percentile, the CSANZ advocates statin ther-
present, CSANZ acknowledges that immediate CAC apy.13 The ESC guidelines promote reclassification of
screening is beneficial to reclassify individual risk.55 patients with CAC >100 and LDL-C levels <70 mg/dL
ESC and NICE guidelines, in contrast, have not put into a high-risk category. Though it is implied, the
forth any recommendations for CAC scoring in in- ESC does not explicitly discuss guidance on statin
dividuals over 75 years of age.11,12 As Chinese and therapy after up-risking patients.11
Japanese guidelines do not specifically discuss CAC The Japanese guidelines acknowledge the benefit
score with age stratification, these CPGs do not for CAC score in adjudicating statin use. However,
include CAC guidelines for younger or older the agency notes a need for further studies to un-
populations.19,26 derstand the prognostic value of CAC in predicting
CVD morbidity and mortality among their unique
CAC IN GUIDING STATIN THERAPY Japanese population.15 The correlation of CAC with
nuclear magnetic resonance measurements was
CAC as a mean to guide statin therapy is a vital pro- comparable but not significant when compared with
ponent among the international CPGs reviewed standard lipids.26 Thus, Japanese CPGs provide no
in this paper, as indicated in Table 2. CAC screening further information on CAC score and statin ther-
is an effective reclassification tool to categorize apy. Instead, they utilize cholesterol levels and
asymptomatic patients into low-, intermediate-, and Suita scores to guide recommendations for
high-risk groups. CAC is an essential platform for pharmacotherapy. 15
CAC IN GUIDING ASPIRIN THERAPY ACC/AHA’s and ESC/EAS’s criteria for low-dose
aspirin therapy may benefit from CAC score quanti-
Next, this review transitions to discuss aspects of fication and subsequent individualized aspirin allo-
downstream care after CAC testing, including cation. Applying the American and European
aspirin and blood pressure management. It is recommendations alongside CAC empowers a
important to note that specialty guidelines (ie, the personalized approach for aspirin therapy in primary
NLA) have, of course, covered these topics at great ASCVD prevention.
length. However, the main international guidelines The NICE, in contrast, considers aspirin therapy
largely do not comment. In this regard, it is also only if the patient’s chest pain is likely stable
important to recognize that many papers reviewed angina. 12 The UK guidelines strongly assert that
here were released after the original guideline doc- routine antiplatelet treatment is not appropriate for
uments were published. Thus, many specialized primary CVD prevention, except for those with high
recommendations for aspirin and antihypertensive stroke or myocardial infarction risk. 12 In this regard,
therapy in context of CAC testing, for instance, the NICE only specifies CAC as a tool for adjudicating
could not have been included within the less statin allocation; CAC recommendations for aspirin
recently updated CPGs. use are not mentioned. Similarly, the Japanese
Like with statin treatment, CAC is an important guidelines do not discuss CAC in guiding aspirin
risk adjudicator in guiding aspirin pharmacotherapy therapy.26
among major CPGs worldwide. The ACC/AHA Primary Unlike the aforementioned CPGs, the CSANZ
Prevention Guidelines recommend low-dose aspirin definitively recommends CAC for guiding aspirin
only among adults 40 to 70 years of age (Figure 8, allocation.13 In tandem with statins, the CSANZ sug-
Central Illustration), who have increased ASCVD risk gests that patients at moderately high or high risk
but no heightened bleeding risk.9,57 ESC CPGs simi- based on CAC score (CAC 101-400 and CAC >400,
larly support a daily dose of 70 mg aspirin for pre- respectively) should receive preventive aspirin ther-
vention of ischemic events in CAD patients with or apy. The CSANZ does not recommend either aspirin or
without a history of myocardial infarction. 11 Both statins for CAC <100.13 Like the CSANZ, the Chinese
agencies only recommend aspirin for high-risk pa- guidelines definitively discuss CAC as an arbitrator
tients, although most CHD events occur in low- to for aspirin allocation.60 Chinese CPGs advocate for
intermediate-risk individuals. 9,58 Moreover, neither primary prevention via aspirin for adults 40 to 69
American nor European guidelines suggest an years of age, who have high risk of ischemia and low
explicit means for identifying these patient sub- risk of bleeding. Recommendations state that high-
groups. To this end, numerous studies have since risk ASCVD groups, classified by CAC score $100,
proposed CAC as a well-established means for guid- may consider taking low-dose aspirin (75-100 mg/d)
ing aspirin allocation in primary prevention.57-59 for primary prevention.60
Utilizing aspirin meta-analysis data on CVD relative Like the Australian and Chinese CPGs, the NLA
risk reduction and bleeding risk, Cainzos-Achirica explicitly advocates CAC for guiding aspirin use, as
et al,57 Miedema et al,58 and Greenland et al 3 each indicated in Figure 5 and the Central Illustration. In
conclude that CAC score can identify subcohorts of fact, the NLA statement is one of the few that in-
individuals (in both overall and within estimated risk cludes detailed recommendations on both aspirin and
strata) who may benefit from aspirin therapy. For antihypertensive therapy after CAC testing. At length,
subgroups with CAC $100 (especially those with CAC this guideline discusses the interaction of ASCVD risk
>400), aspirin yields a net benefit regardless of risk and CAC score in predicting net benefit of aspirin
factors. For CAC ¼ 0, however, the risk of bleeding therapy in primary prevention. 16 The NLA cites
remains larger than aspirin’s potential benefit. 3,57,58
Cainzos-Achirica et al57 and numerous others,
59
Ajufo et al similarly determine that aspirin is evidencing that aspirin therapy risks outweigh ben-
beneficial for CAC ¼ 0, only if patients have >20% efits when stratifying patients via ASCVD risk score. 16
ASCVD risk. Regardless of CAC score, aspirin is net In contrast, CAC $100 appears to identify a subgroup
harmful in those with <5% risk or with increased of patients in which benefit of aspirin therapy ex-
bleeding risk. 59 These data contributed to the Amer- ceeds bleeding risk. 16,57 To this end, the NLA advo-
ican SCCT guidelines, which now recommend cates that aspirin 81 mg daily is reasonable for
consideration of aspirin therapy for all individuals patients with CAC $100, who do not have bleeding-
with CAC >100.17 To this end, patients who meet the related contraindications.16
UTILIZING CAC TO GUIDE PHARMACOLOGICAL on CAC with regard to reclassifying blood pressure
TREATMENT OF EARLY HYPERTENSION AND management. Seeing as the papers reviewed previ-
SELECTION OF BLOOD PRESSURE GOALS ously were released after most CPGs were published,
they could not have been included in major guideline
CPGs tend to agree that ASCVD risk assessment in recommendations. Uniquely, the NLA discusses the
guiding the decision to pharmacologically treat early role of CAC score in deciding pharmacological treat-
hypertension is of vital importance. However, like ment of early-stage hypertension at great length. The
many recommendations for aspirin therapy, the in- NLA notes that CAC appears to reclassify risk in pa-
ternational guidelines do not designate coronary tients with stage 1 hypertension and thus may prove
visualization for risk stratification. The ACC/AHA useful for guiding decisions about pharmaco-
suggests ASCVD risk assessment for informing hy- therapy. 16 Specifically, CAC ¼ 220 identifies patients
pertension therapy in adults with elevated blood with annual ASCVD risk similar to those enrolled in
pressure or low-risk stage 1 hypertension, and sug- the SPRINT (Systolic Blood Pressure Intervention
gests that a high CAC may warrant more aggressive Trial) trial. To this point, the NLA advocates that CAC
blood pressure control.61 European guidelines simi- may be useful in guiding blood pressure targets. 16
larly concur that CV risk assessment systems are vital
but still recommend PCE for management of arterial IMPORTANT ASPECTS AND QUALITY
hypertension. 62
Instead of suggesting coronary visu- IMPROVEMENT OF CURRENT CLINICAL
alization via CAC, the ESC designates the SCORE CAC APPLICATIONS
system to adjudicate risk level and inform antihy-
pertensive therapy.62 Similarly, none of the Cana- CAC COST AND INSURANCE COVERAGE. The CAC
dian, Australian, UK, Chinese, or Japanese CPGs test averages 10 minutes total for the patient,
specify CAC to help allocate hypertension treatment. including about 1 minute of actual scan time. Calcium
Especially for an intermediate-risk cohort, stratifica- score screenings are now covered more widely, as the
tion of risk and subsequent therapy remains unclear 2018 guidelines included this test within their algo-
among these international agencies. rithm of care. Anthem, UnitedHealthcare, and Aetna
A multitude of literature, however, has since all have favorable coverage decisions, and Medicare
analyzed CAC as a tool to help inform the selection of pays in certain states. Texas covers CAC scanning by
blood pressure goals and decide the pharmacological state law. However, most HMOs and some insurance
treatment of early hypertension. The current contro- carriers still do not cover this test, and for those pa-
versy over optimal SBP threshold for initiating or tients, it may be available only on a self-pay basis. This
intensifying treatment spurs questions about whom cash price ranges from approximately $75 to $250.
to treat, particularly among intermediate-risk pa-
BARRIERS TO ADOPTION OF GUIDELINES. The main
tients with prehypertension or mild hypertension. 30
barrier of utilizing CAC score is lack of coverage by
In this regard, there is heightened interest in global
many health insurance plans and its designation by
ASCVD risk estimates alongside SBP to guide
these companies as experimental. Radiation exposure
personalized therapy. McEvoy et al,30 for instance,
(although minimal at <1 mSv) is another concern, but
compared multivariable-adjusted HRs for ASCVD or
this is largely due to citing of earlier doses, which are
heart failure, after stratifying by CAC. The project
higher and no longer relevant.
found that coronary calcium stratifies event risk in
patients with SBP <160 mm Hg. 30 Increasing HRs STRATEGIES TO INCREASE UTILIZATION. CPGs from
were found for events with CAC 1 to 100 (HR: 1.7 the United States and Europe have universally rec-
[95% CI: 1.0-2.6] or HR: 2.0 [95% CI: 1.1-3.8]) and CAC ommended risk factor equations that use office-based
>100 (HR: 3.0 [95% CI: 1.8-5.0] or HR: 5.7 [95% CI: 2.9- measurements of age, smoking history, presence or
11.0]), all relative to CAC ¼ 0. 30
In this regard, absence of diabetes, blood lipids, and blood pressure
combining CAC score with assessment of ASCVD risk as mainstays of clinical risk assessment. Moreover, all
offers a tool to guide personalized SBP goals in American and European CPGs now include CAC in
intermediate-risk subgroups. 30,61
For statins, aspirin, their risk assessment. To this end, CAC will
and antihypertensive therapies, CAC offers a poten- undoubtably increase in utilization as physicians
tially crucial model to identify candidates who may begin to adapt to the new clinical pathways.
benefit from initiation or intensification of medical IS THERE A NEED FOR FURTHER TRIALS? Based on
management. single-center and multicenter clinical and
As noted previously with aspirin management, the population-based studies with short-term and long-
main international guidelines largely do not comment term outcomes data (up to 15 years’ follow-up), CAC
scoring has emerged as a widely available, consistent,

HIGHLIGHTS
and reproducible means of assessing risk of major CV
outcomes. CAC has proven especially useful in Guidelines worldwide emphasize the
asymptomatic people for planning primary preven- importance of CAC in up- or down-risking
tion interventions such as statins and aspirin. Addi- of patients for ASCVD risk and for
tional research and rigorous data are vital for younger initiating or prolonging preventive
age groups and the female population. pharmacotherapies.
Ongoing randomized trials in Europe, United
International guidelines empower a
States, and Australia studying CAC versus no CAC to
dynamic clinician-patient relationship
evaluate for outcomes will answer any lingering
and advocate for individualized discus-
questions about the utility of the test, and these are
sions regarding disease management and
due out in the next few years. One such ongoing
pharmacotherapy treatment.
European trial is the DANCAVAS (Danish Cardiovas-
cular Screening) trial, investigating whether multi- Understanding the parallels among
faceted advanced CV screening will prevent CV international CAC guidelines is essential
events and whether possible health benefits are cost- for clinicians to individualize further
effective.63 The ROBINSCA (Risk or Benefit IN medical management.
Screening for CArdiovascular Disease) trial is awaiting
final outcome results, after comparing traditional risk
scores versus CAC.64 American trials are also exten- making between clinician and patient. With these
sive, including the CorCal (Effectiveness of a Proac- commonalities in mind, international medical prac-
tive Cardiovascular Primary Prevention Strategy, tice should be rooted on early detection of individuals
With or Without the Use of Coronary Calcium with increased CVD risk via CAC score.
Screening, in Preventing Future Major Adverse Car- This review does find some differences in precise
diac Events) trial.65 The ongoing CorCal trial tests CAC score intervals, risk cut points, treatment
effectiveness of a proactive CV primary prevention thresholds, and stratifiers of specific patient
strategy with or without CAC, compared with current subgroups among international guidelines (Central
standard care in preventing major adverse cardiac Illustration, Figure 3, Table 1). Understanding both
events.65 Also ongoing is the ACCURATE (Assessment similarities and differences among international CPGs
of Patients With suspeCted Coronary Artery Disease is therefore vital for physicians to correctly determine
by Coronary calciUm fiRst strATegy vErsus Usual Care personalized statin therapy and subsequent man-
Approach) trial, examining whether a CAC-first agement. It is imperative to unify universal ASCVD
strategy may be used as a gatekeeper for progres- risk assessment and establish global solutions for
sion to the cardiac positron emission tomography CPGs on CAC scoring. Notably, this review un-
stress test. Australian CAUGHT-CAD (Coronary Artery derscores that additional research and rigorous data
calcium score: Use to Guide management of are vital for younger age groups and the female pop-
Hereditary Coronary Artery Disease) trial examines ulation. By summarizing the framework behind global
coronary calcium for risk evaluation and prevention guidelines of CAC in ASCVD risk assessment, this
in patients with a family history of CAD. 66 analysis allows for applications in both the clinical
Last, there is also an interest in studying role of setting and preventive therapy. Helping physicians
CAC in predicting non-CVD outcomes. CAC has been understand universal differences and similarities is
shown to predict CKD, chronic obstructive pulmonary key to refine risk detection, focus preventive strate-
disease, hip fracture, cancer, and dementia indepen- gies of care, and empower the most fitting choices in
dent of age, sex, and risk factors.3 CVD prevention and management.
CONCLUSIONS AND CLINICAL IMPLICATIONS

FUNDING SUPPORT AND AUTHOR DISCLOSURES
In summary, the CPGs compared in this review hold The authors have reported that they have no relationships relevant to
more similarities than differences from both a clinical the contents of this paper to disclose.
and practical perspective (Central Illustration,
Figure 3, Table 1). All CPGs recommend statins for ADDRESS FOR CORRESPONDENCE: Dr Matthew J.
primary prevention and CAC as a reasonable risk Budoff, Lundquist Institute at Harbor-UCLA Medical
adjudicator. Importantly, clinical practice recom- Center, 1124 West Carson Street, Torrance, California
mendations worldwide emphasize shared decision 90502, USA. E-mail: mbudoff@lundquist.org.
REFERENCES
1. Pagidipati NJ, Gaziano TA. Estimating deaths 13. Liew G, Chow C, van Pelt N, et al. Cardiac So- 2019;62(5):423–430. https://doi.org/10.1016/j.
from cardiovascular disease: a review of global ciety of Australia and New Zealand position pcad.2019.10.007
methodologies of mortality measurement. Circu- statement: coronary artery calcium scoring. Heart
23. Hamilton-Craig CR, Cho CK, Younger JF,
lation. 2013;127(6):749–756. https://doi.org/10. Lung Circ. 2017;26(12):1239–1251. https://doi.org/
Jelinek VM, Chan J, Liew GY. Cardiac Society of
1161/CIRCULATIONAHA.112.128413 10.1016/j.hlc.2017.05.130
Australia and New Zealand position statement
2. Roth GA, Mensah GA, Johnson CO, et al. 14. Joint Committee for Guideline Revision. 2016 executive summary: coronary artery calcium
Global burden of cardiovascular diseases and risk Chinese guidelines for the management of dysli- scoring. Med J Aust. 2017;2017(8):357–361.
factors, 1990-2019: update from the GBD 2019 pidemia in adults. J Geriatr Cardiol. 2018;15(1):1– https://doi.org/10.5694/mja16.01134
study. J Am Coll Cardiol. 2020;276(25):2982– 29.
24. McDonagh TA, Metra M, Adamo M, et al. ESC
3021. 15. Kinoshita M, Yokote K, Arai H, et al. Japan Scientific Document Group. 2021 ESC guidelines
3. Greenland P, Blaha MJ, Budoff MJ, Erbel R, Atherosclerosis Society (JAS) guidelines for pre- for the diagnosis and treatment of acute and
Watson KE. Coronary calcium score and vention of atherosclerotic cardiovascular diseases chronic heart failure: developed by the task force
cardiovascular risk. J Am Coll Cardiol. 2017. J Atheroscler Thromb. 2018;25(9):846–894. for the diagnosis and treatment of acute and
2018;72(4):434–447. https://doi.org/10.1016/j. https://doi.org/10.5551/jat.GL2017 chronic heart failure of the European Society of
jacc.2018.05.027 Cardiology (ESC) With the special contribution of
16. Orringer CE, Blaha MJ, Blankstein R, et al. The
the Heart Failure Association (HFA) of the ESC. Eur
National Lipid Association scientific statement on
4. Golub I, Lakshmanan S, Dahal S, Budoff MJ.
coronary artery calcium scoring to guide preven- Heart J. 2021;42(36):3599–3726. https://doi.org/
Utilizing coronary artery calcium to guide statin
tive strategies for ASCVD risk reduction. J Clin 10.1093/eurheartj/ehab368
use. Atherosclerosis. 2021;326:17–24. https://doi.
org/10.1016/j.atherosclerosis.2021.04.011 Lipidol. 2021;15(1):33–60. https://doi.org/10. 25. Budoff MJ, Young R, Burke G, et al. Ten-year
1016/j.jacl.2020.12.005 association of coronary artery calcium with
5. Michos ED, Blaha MJ, Blumenthal RS. Use of the atherosclerotic cardiovascular disease (ASCVD)
17. Hecht H, Blaha MJ, Berman DS, et al. Clinical
coronary artery calcium score in discussion of events: the Multi-Ethnic Study of Atherosclerosis
indications for coronary artery calcium scoring in
initiation of statin therapy in primary prevention. (MESA). Eur Heart J. 2018;39(25):2401–2408.
asymptomatic patients: expert consensus state-
Mayo Clin Proc. 2017;92(12):1831–1841. https://
ment from the Society of Cardiovascular 26. Yamamoto H, Kitagawa T, Kihara Y. Clinical
doi.org/10.1016/j.mayocp.2017.10.001
Computed Tomography. J Cardiovasc Comput implications of the coronary artery calcium score
6. Field MJ, Lohr KN. Guidelines for Clinical Prac- Tomogr. 2017;11:157–168. in Japanese patients. J Atheroscler Thromb.
tice: From Development to Use. National Academy 2014;21(11):1101–1108. https://doi.org/10.5551/
18. U.S. Preventive Services Task Force, Curry SJ,
Press; 1992. jat.26427
Krist AH, Owens DK, et al. Risk assessment for
7. Martin SS, Sperling LS, Blaha MJ, et al. Clinician- cardiovascular disease with nontraditional risk 27. Jellinger PS, Handelsman Y, Rosenblit PD,
patient risk discussion for atherosclerotic cardio- factors: U.S. Preventive Services Task Force et al. American Association of Clinical Endocri-
vascular disease prevention: importance to Recommendation Statement. JAMA. 2018;320(3): nologists and American College of Endocrinology
implementation of the 2013 ACC/AHA guidelines. 272–280. https://doi.org/10.1001/jama.2018. guidelines for management of dyslipidemia and
J Am Coll Cardiol. 2015;65(13):1361–1368. 8359 prevention of cardiovascular disease. Endocr Pract.
19. Chinese Society of Cardiology of Chinese 2017;23(suppl 2):1–87. https://doi.org/10.4158/
8. Morris PB, McLain K. What the guidelines do not
Medical Association, Cardiovascular Disease Pre- EP171764.APPGL
say: statin nonbenefit groups. Curr Atheroscler
Rep. 2015;17(1):468. vention and Rehabilitation Committee of Chinese 28. Newman CB, Blaha MJ, Boord JB, et al. Lipid
Association of Rehabilitation Medicine, Cardio- management in patients with endocrine disorders:
9. Arnett DK, Blumenthal RS, Albert MA, et al.
vascular Disease Committee of Chinese Associa- an Endocrine Society clinical practice guideline.
2019 ACC/AHA guideline on the primary preven-
tion of Gerontology and Geriatrics, Thrombosis J Clin Endocrinol Metab. 2020;105(12):dgaa674.
tion of cardiovascular disease: executive summary:
Prevention and Treatment Committee of Chinese https://doi.org/10.1210/clinem/dgaa674
a report of the American College of Cardiology/
Medical Doctor Association, Hu D, Han Y, Ning G,
American Heart Association Task Force on Clinical 29. Gopal A, Nasir K, Liu ST, Flores FR, Chen L,
Ma C. Chinese guideline on the primary prevention
Practice Guidelines. J Am Coll Cardiol. Budoff MJ. Coronary calcium progression rates
of cardiovascular diseases. Cardiol Discov.
2019;74(10):1376–1414. https://doi.org/10.1016/j. with a zero initial score by electron beam to-
2021;1(2):70–104. https://doi.org/10.1097/CD9.
jacc.2019.03.009 mography. Int J Cardiol. 2007;117:227–231.
0000000000000025
10. Pearson GJ, Thanassoulis G, Anderson TJ, et al. 30. McEvoy JW, Martin SS, Dardari ZA, et al.
20. Piepoli MF, Hoes AF, Agewall S, et al. 2016
2021 Canadian Cardiovascular Society guidelines Coronary artery calcium to guide a personalized
European guidelines on cardiovascular disease
for the management of dyslipidemia for the pre- risk-based approach to initiation and intensifica-
prevention in clinical practice: the Sixth Joint Task
vention of cardiovascular disease in the adult. Can tion of antihypertensive therapy. Circulation.
Force of the European Society of Cardiology and
J Cardiol. 2021;37(8):1129–1150. https://doi.org/ 2017;135:153–165.
Other Societies on Cardiovascular Disease Pre-
10.1016/j.cjca.2021.03.016 vention in Clinical Practice (constituted by repre- 31. Grundy SM, Stone NJ, Bailey AL, et al. 2018
11. Authors/Task Force Members; ESC Committee sentatives of 10 societies and by invited experts) AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/
for Practice Guidelines (CPG); ESC National Cardiac developed with the special contribution of the APhA/ASPC/NLA/PCNA guideline on the manage-
Societies. 2019 ESC/EAS guidelines for the man- European Association for Cardiovascular Preven- ment of blood cholesterol: a report of the Amer-
agement of dyslipidaemias: lipid modification to tion & Rehabilitation (EACPR). Eur Heart J. ican College of Cardiology/American Heart
reduce cardiovascular risk. Atherosclerosis. 2016;37:2315–2381. Association Task Force on Clinical Practice Guide-
2019;290:140–205. https://doi.org/10.1016/j. lines. J Am Coll Cardiol. 2019;73:3168–3209.
21. Bartlomiejczyk MA, Penson P, Banach M.
atherosclerosis.2019.08.014 Worldwide dyslipidemia guidelines. Curr Car- 32. Blaha MJ, Whelton SP, Al Rifai M, et al.
diovasc Risk Rep. 2019;13:2. https://doi.org/10. Comparing risk scores in the prediction of coronary
12. National Institute for Health and Care Excel-
1007/s12170-019-0597 and cardiovascular deaths: Coronary Artery Cal-
lence. Addendum to Clinical Guideline (CG95),
cium Consortium. J Am Coll Cardiol Img.
chest pain of recent onset: assessment and diag- 22. Dzaye O, Dudum R, Reiter-Brennan C, et al.
2021;14(2):411–421. https://doi.org/10.1016/j.
nosis. Clinical Guideline CG95.1. Methods, evi- Coronary artery calcium scoring for individualized
jcmg.2019.12.010
dence and recommendation. Accessed August 9, cardiovascular risk estimation in important patient
2022. https://www.nice.org.uk/guidance/cg95/ subpopulations after the 2019 AHA/ACC primary 33. Quispe R, Ferraro RA, Cainzos-Achirica M, et al.
update/cg95-update-1/documents/addendum prevention guidelines. Prog Cardiovasc Dis. Risk assessment for cardiovascular disease
prevention: comparing the American and European cholesterol lowering, blood pressure lowering, the ESC/EAS guidelines. Mayo Clinic Proc.
approaches. American College of Cardiology; antithrombotic therapy, and smoking cessation in 2020;95(5):998–1014. https://doi.org/10.1016/j.
Accessed August 9, 2022. https://www.acc.org/ apparently healthy people. Eur Heart J. mayocp.2020.01.011
latest-in-cardiology/articles/2019/11/21/ 2020;41(11):1190–1199. https://doi.org/10.1093/
57. Cainzos-Achirica M, Miedema MD, McEvoy JW,
07/26/risk-assessment-for-cardiovascular- eurheartj/ehz239
et al. Coronary artery calcium for personalized
disease-prevention
45. Stompór T. Coronary artery calcification in allocation of aspirin in primary prevention of car-
34. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. chronic kidney disease: An update. World J Cardiol. diovascular disease in 2019: the MESA study
2013 ACC/AHA guideline on the assessment of 2014;6(4):115–129. https://doi.org/10.4330/wjc. (Multi-Ethnic Study of Atherosclerosis). Circula-
cardiovascular risk: a report of the American Col- v6.i4.115 tion. 2020;141(19):1541–1553. https://doi.org/10.
lege of Cardiology/American Heart Association 1161/CIRCULATIONAHA.119.045010
46. Tota-Maharaj R, Blaha MJ, McEvoy JW, et al.
Task Force on Practice Guidelines. J Am Coll Car- 58. Miedema MD, Duprez DA, Misialek JR, et al.
Coronary artery calcium for the prediction of mor-
diol. 2014;63(25 Pt B):2935–2959.
tality in young adults <45 years old and elderly Use of coronary artery calcium testing to guide
35. McClelland RL, Jorgensen NW, Budoff M, et al. adults >75 years old. Eur Heart J. 2012;33(23):2955– aspirin utilization for primary prevention: esti-
10-Year coronary heart disease risk prediction us- 2962. https://doi.org/10.1093/eurheartj/ehs230 mates from the Multi-Ethnic Study of Athero-
ing coronary artery calcium and traditional risk sclerosis. Circ Cardiovasc Qual Outcomes.
47. Dzaye O, Al Rifai M, Dardari Z, et al. Coronary
factors: derivation in the MESA (Multi-Ethnic 2014;7(3):453–460. https://doi.org/10.1161/CIR-
artery calcium as a synergistic tool for the age-
Study of Atherosclerosis) with validation in the COUTCOMES.113.000690
and sex-specific risk of cardiovascular and cancer
HNR (Heinz Nixdorf Recall) Study and the DHS mortality: the Coronary Artery Calcium Con- 59. Ajufo E, Ayers CR, Vigen R, et al. Value of
(Dallas Heart Study). J Am Coll Cardiol. sortium. J Am Heart Assoc. 2020;9(8):e015306. coronary artery calcium scanning in association
2015;66(15):1643–1653. https://doi.org/10.1161/JAHA.119.015306 with the net benefit of aspirin in primary preven-
36. Marma AK, Berry JD, Ning H, Persell SD, tion of atherosclerotic cardiovascular disease.
48. Shaw LJ, Min JK, Nasir K, et al. Sex differences
Lloyd-Jones DM. Distribution of 10-year and life- JAMA Cardiol. 2021;6(2):179–187. https://doi.org/
in calcified plaque and long-term cardiovascular
time predicted risks for cardiovascular disease in 10.1001/jamacardio.2020.4939
mortality: observations from the CAC Consortium.
US adults: findings from the National Health and Eur Heart J. 2018;39(41):3727–3735. https://doi. 60. Li XY, Shi ZW, Zhao D, Yin DW, writing group
Nutrition Examination Survey 2003 to 2006. Circ org/10.1093/eurheartj/ehy534 of. 2019 Chinese expert consensus statement on
Cardiovasc Qual Outcomes. 2009;3:8–14. aspirin application in primary prevention of car-
49. Bellasi A, Lacey C, Taylor AJ, et al. Comparison
37. JBS3 Board. Joint British Societies’ consensus diovascular disease. 2019 Chinese expert
of prognostic usefulness of coronary artery cal-
recommendations for the prevention of cardio- consensus statement on aspirin application in
cium in men versus women (results from a meta-
vascular disease (JBS3). Heart. 2014;100(suppl 2): primary prevention of cardiovascular disease. Chin
and pooled analysis estimating all-cause mortality
ii1–ii67. Med J (Engl). 2020;133(10):1221–1223. https://doi.
and coronary heart disease death or myocardial
org/10.1097/CM9.0000000000000762
38. Dorresteijn JA, Visseren FL, Wassink AM, et al. infarction). Am J Cardiol. 2007;100(3):409–414.
https://doi.org/10.1016/j.amjcard.2007.03.037 61. Parcha V, Malla G, Kalra R, et al. Coronary ar-
Development and validation of a prediction rule
tery calcium score for personalization of antihy-
for recurrent vascular events based on a cohort 50. Michos ED, Nasir K, Braunstein JB, et al. Fra-
pertensive therapy: a pooled cohort analysis.
study of patients with arterial disease: the SMART mingham risk equation underestimates subclinical
Hypertension. 2021;77(4):1106–1118. https://doi.
risk score. Heart. 2013;99:866–872. atherosclerosis risk in asymptomatic women.
org/10.1161/HYPERTENSIONAHA.120.16689
39. Kengne AP, Patel A, Marre M, et al. Contem- Atherosclerosis. 2006;184:201–206.
62. Williams B, Mancia G, Spiering W, et al, ESC
porary model for cardiovascular risk prediction in 51. Lakoski SG, Greenland P, Wong ND, et al.
Scientific Document Group. 2018 ESC/ESH guide-
people with type 2 diabetes. Eur J Cardiovasc Prev Coronary artery calcium scores and risk for car-
lines for the management of arterial hypertension:
Rehabil. 2011;18:393–398. diovascular events in women classified as "low
the task force for the management of arterial hy-
40. NIPPON DATA80 Research Group. Risk risk" based on Framingham risk score: the Multi-
pertension of the European Society of Cardiology
assessment chart for death from cardiovascular Ethnic Study of Atherosclerosis (MESA). Arch
(ESC) and the European Society of Hypertension
disease based on a 19-year follow-up study of a Intern Med. 2007;167:2437–2442.
(ESH). Eur Heart J. 2018;39(33):3021–3104.
Japanese representative population. Circ J. 52. Okwuosa TM, Greenland P, Ning H, Liu K, https://doi.org/10.1093/eurheartj/ehy339
2006;70(10):1249–1255. Lloyd-Jones DM. Yield of screening for coronary
63. Diederichsen ACP, Rasmussen LM, Søgaard R,
41. Nakai M, Miyamoto Y, Higashiyama A, et al. artery calcium in early middle-age adults based on
et al. The Danish Cardiovascular Screening Trial
EPOCH-JAPAN Research Group. Calibration be- the 10-year Framingham risk score: the CARDIA
(DANCAVAS): study protocol for a randomized
tween the estimated probability of the risk study. J Am Coll Cardiol Img. 2012;5, 923-923.
controlled trial. Trials. 2015;16:554. https://doi.
assessment chart of Japan atherosclerosis society 53. Chua A, Blankstein R, Ko B. Coronary artery org/10.1186/s13063-015-1082-6
and actual mortality using external population: calcium in primary prevention. Aust J Gen Prac.
64. Van Der Aalst C, Denissen SJAM, Vonder M,
Evidence for cardiovascular prevention from 2020;49(8):464–469. https://doi.org/10.31128/
et al. ROBINSCA. Risk results from screening for a
observational cohorts in Japan (EPOCH-JAPAN). AJGP-03-20-527
high cardiovascular disease risk by means of
J Atheroscler Thromb. 2016;23:176–195.
54. Abdalla KM, Aleshawi AJ, Hinawi Y, Bani traditional risk factor measurement or coronary
42. Liu J, Hong Y, D’Agostino RB Sr, et al. Pre- Hani D, Ababneh AA. Coronary artery anomalies in artery calcium scoring in the ROBINSCA trial. Eur
dictive value for the Chinese population of the patients with zero calcium score: a new evidence Heart J. 2020;41(suppl_2):2959. https://doi.org/
Framingham CHD risk assessment tool compared supports the 2016-NICE guidance. Eur J Radiol 10.1093/ehjci/ehaa946.2959. ehaa946.
with the Chinese Multi-Provincial Cohort Study. Open. 2020;7:100211. https://doi.org/10.1016/j.
65. Muhlestein J, Knowlton K, Le V, et al. Effect
JAMA. 2004;291(21):2591–2599. https://doi.org/ ejro.2019.12.005
on patient adherence to primary prevention: rec-
10.1001/jama.291.21.2591
55. Jennings GLR, Audehm R, Bishop W, et al. ommendations for statin therapy based on the
43. Joint committee issued Chinese guideline for National Heart Foundation of Australia: position National Guidelines-supported pooled cohort risk
the management of dyslipidemia in adults. 2016 statement on coronary artery calcium scoring for equation or a coronary artery calcium score: pre-
Chinese guideline for the management of dyslipi- the primary prevention of cardiovascular disease in liminary findings from the Vanguard study for the
demia in adults]. Zhonghua Xin Xue Guan Bing Za Australia. Med J Aust. 2021;214(9):434–439. CorCal randomized clinical outcomes trial. J Am
Zhi. 2016;44(10):833–853. https://doi.org/10. https://doi.org/10.5694/mja2.51039 Coll Cardiol. 2020;75(11_suppl_1):5. https://doi.
3760/cma.j.issn.0253-3758.2016.10.005 org/10.1016/S0735-1097(20)30632-X
56. Singh M, McEvoy JW, Khan SU, et al. Com-
44. Jaspers N, Blaha MJ, Matsushita K, et al. parison of transatlantic approaches to lipid man- 66. Venkataraman P, Marwick T, Huynh Q,
Prediction of individualized lifetime benefit from agement: the AHA/ACC/Multisociety guidelines vs CAUGHT-CAD Investigators. Using coronary artery
calcium to guide cardiovascular risk reduction: Association Task Force on Clinical Practice Guide- (CCS), cardiovascular disease, Cardiac
insights from the CAUGHT-CAD trial. Eur Heart J. lines. J Am Coll Cardiol. 2019;73(24):e285–e350. Society of Australia and New Zealand
2020;41(suppl_2):2950. https://doi.org/10.1093/ https://doi.org/10.1016/j.jacc.2019.11.003 (CSANZ), Clinical Practice Guidelines,
ehjci/ehaa946.2950 computed tomography angiography,
67. Grundy SM, Stone NJ, Bailey AL, et al. 2018 coronary artery calcium, European Society
AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ KEY WORDS American College of for Cardiology/European Atherosclerosis
APhA/ ASPC/NLA/PCNA guideline on the man- Cardiology/American Heart Association Society (ESC/EAS), Japanese Atherosclerosis
agement of blood cholesterol: a report of the (ACC/AHA), atherosclerotic cardiovascular Society (JAS), National Institute for Health
American College of Cardiology/American Heart disease, Canadian Cardiovascular Society and Care Excellence (NICE)

Major Global Coron Art Calcium CAC Guidel SOTA Golub JACC 2023

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Major Global Coron Art Calcium CAC Guidel SOTA Golub JACC 2023

Uploaded by

Copyright:

Available Formats

JACC: CARDIOVASCULAR IMAGING VOL. 16, NO.

ª 2023 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

Major Global Coronary Artery

C ardiovascular disease (CVD) is a leading

ISSN 1936-878X/$36.00 https://doi.org/10.1016/j.jcmg.2022.06.018

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

F I G U R E 1 The ACC/AHA Guidelines Recommend CAC for ASCVD Risk Stratiﬁcation

LDL-C ≥190 mg/dL (≥4.9 mmol/L)

Age 20-39 y Diabetes mellitus and age 40-75 y

ASCVD Risk Enhancers:

In Selected Individuals if Measured:

C ENTR AL I LL U STRA T I O N Summary of Major Global CAC Guidelines

• CAC as an • CAC as a tool for • CAC scoring to up- • CAC as a risk

Common Indications Common Treatment Nonagreement

Golub IS, et al. J Am Coll Cardiol Img. 2023;16(1):98–117.

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

F I G U R E 2 The CCS Guidelines Recommend CAC for ASCVD Risk Stratiﬁcation

Low-Risk* Intermediate Risk* High-Risk*

Statin therapy not recommended for Discuss health behavior modifications

If LDL-C >2.0 mmol/L or apoB >0.8 g/L or

F I G U R E 3 Key Agreements Among Guidelines

Common Common Treatment Non-Agreement

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

also classiﬁes speciﬁc CAC risk thresholds to adjudi-

T A B L E 2 CAC in Guiding Statin Use

ACC/AHA Downgrade risk, Favors statin $55 Initiate statin therapy —

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

F I G U R E 4 The CSANZ Guidelines Recommend CAC for ASCVD Risk Stratiﬁcation

Framingham Risk Score

Low risk <10% Intermediate risk High Risk >20%

Strong family history,

F I G U R E 5 The NLA Guidelines Endorse CAC

Family History Diabetes mellitus, Primary LDL-C Adults 76-80

Adults < age 40 Adults age

<5% risk and CAC = 0

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

a paramount risk factor in the predictive model of 10-

CAC RECOMMENDATIONS IN SPECIAL

Confirm low-risk CHRONIC KIDNEY DISEASE. In those with CKD, a

Score Risk Treatment Recommendation

0 very low statin not recommendeda

moderate intensity statin if <75th%;

100-299 moderately increased moderate to high intensity statin + ASA 81 mg

>300 moderate to severely increased high intensity statin + ASA 81 mg

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

risk. The ACC/AHA, CSANZ, ESC/EAS, and CCS

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

scoring has emerged as a widely available, consistent,

CONCLUSIONS AND CLINICAL IMPLICATIONS

Major Global Coronary Artery Calcium Guidelines JANUARY 2023:98–117

You might also like