A Picture is Worth a Thousand Words: Coronary Artery Calcium Scores
Case Presentations:
Patient A:
A 40 year old healthy male presents to the cardiology clinic. He has been diligent about exercising regularly due to his family history of heart disease.
Patient: “My dad died of a heart attack while playing tennis at age 61 and he was really fit and I don’t want that to happen to me. So, I got a Calcium CT scan and my CAC score is 32. Is that bad, because it says it’s just mild?”
Cardiologist: “It’s pretty low, so we don’t need to worry about it yet. Let’s keep an eye on it.”
Patient: “But I went to this website called Multi-Ethnic Study of Atherosclerosis and plugged it into this Calcium Calculator and even if I were 45 I’d be at the 89th percentile rank. That sounds bad. Shouldn’t I do something about that now?”
Patient B:
A 62 year old female presents to the cardiology clinic. She has been an avid triathlete out of concern for her family history of heart disease.
Patient: “My mother died of a massive heart attack at 62 so I decided I should get one of those screening Calcium CT scans. I was shocked but not surprised when it came back super high at 1300! I should’ve known it’s in my genes. I’m really scared but I really don’t want to take any drugs. I prefer a natural approach.”
Cardiologist: “I don’t believe in those scores. There’s never been a randomized controlled trial showing any benefit to a calcium score. Are you having any symptoms, like chest pain?”
Patient: No.
Cardiologist: “Don’t worry about it. Your cholesterol ratio looks great! (What's Your ApoB? A Practical Approach to Lipid Management). Check out my supplements on the way out - I just restocked the Vitamin K2 and that’ll help the calcification you’re worried about. Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT | JACC: Advances. By the way, when’s your next triathlon? Killer Workouts - The Adult Athlete
Flying Under the Radar
Low CAC Scores Fail To Receive Appropriate Treatment
While a low calcium score may impart low short term risk in an elderly patient, for instance, it may represent high lifetime risk in a young person (> 75th percentile for age, gender, race); placing them on a high risk trajectory for ASCVD complication to include cardiovascular death over the next, say, 30 years.
Sadly, many young patients with a “low CAC score,” but high percentile rank (>75th), have been misinformed to simply “keep an eye on it” because it’s “not high yet.” That’s not good advice, considering we know that the earlier we initiate intense treatment, the more likely we are to get in front of the disease and prevent a lifetime of ASCVD complications.
Coronary artery calcium scores carry a “warranty” of about 5-10 years. The Agatston score informs upon an individual’s near-term, or 10 year cardiovascular risk.
However, when compared to others of the same age, gender and race, it also provides a percentile rank and informs us of one’s “lifetime” risk, or “30-year” risk.
Many facilities use the risk calculator programmed into the CT scanner, which is often outdated and underestimates risk. MESA Calcium Calculator is preferred.
High CAC Scores Fail to Receive the Aggressive Treatment Needed
After decades of needless controversy, corruption and conspiracy (Watch The Widowmaker | Prime Video), multiple guidelines have finally embraced coronary artery calcium scores as part of the ASCVD risk stratification process. Tragically, there are many providers, to include specialists like cardiologists, who remain unconvinced, still holding out for some sort of RCT before embracing this technology that allows one to actually “see” the disease within the coronaries.
Long standing endurance athletes have been identified as a subgroup that may have a predilection for higher coronary artery calcium scores. This may in part explain the seemingly paradoxical phenomenon of sudden cardiac death during endurance races. Athletes may have a false sense of optimal health (healthy athlete bias) and either fail to obtain proper screening, or feel they can treat it solely through natural means - like “running” away from it. See Killer Workouts - The Adult Athlete.
In other cases a high CAC score may give some patients a false sense of doom, causing them to perhaps even withdraw from optimal medical therapy due to the belief that nothing can be done, or that “it’s in my genes - everyone in my family had this.” Many patients read the report and falsely conclude that they are destined to have a heart attack. Comments like “it says here I have a 99% chance of having a heart attack in 10 years” are not uncommon.
It’s important to communicate that no CAC score or percentile rank “guarantees” or “obligates” a person to having a future heart attack or stroke, but it does put them in good company with those who do when nothing is done about it. It is not a time to feel depressed about the diagnosis, but a time to feel fortunate that the diagnosis has been made before an ASCVD event has occurred knowing we have safe and effective therapies proven to halt and even regress atherosclerosis.
CardioAdvocate Checklist:
Calculate 10 year ASCVD Risk - many calculators out there
Mayo Clinic Statin Choice Decision Aid: Statin Choice Decision AID - Site
Contains multiple Risk calculators to include:
ACC/AHA PCE
Reynolds (includes family history and hs CRP)
Framingham
HeartScore (European)
2018 ACC/AHA Guidelines: Adults 40-75 years w/o diabetes
10 year risk ≥ 7.5%
start moderate-intensity statin
Patients reluctant to take statins
check CAC
Prior statin-related symptoms, contemplating restarting statin
Check CAC
If risk uncertain, obtain CAC
Older patients (M 55-80y, F 60-80y) w/ low burden of risk factors
Middle aged adults (40-55 y) with 10 year risk ASCVD 5-7.5%
If statin indicated, reduce LDL-C levels by ≥ 30%
If 10 yr risk ≥ 20%, reduce LDL-C levels by ≥ 50%
If CAC = 0, statins may be withheld
Except smokers, those with DM, those with strong family history of ASCVD
CAC 1-99: favors statin (especially if age > 55)
CAC ≥ 100 Agatston units - statin indicated
CAC ≥ 75% rank - statin indicated
Anyone under age 50 with CAC > 0 represents high lifetime risk and intervention is warranted
CAC ≥ 300: Risk equivalent to “Heart Attack Survivors” Adults with high CAC score at similar risk for CV events as those with established ASCVD
Secondary prevention measures ought to be employed
Advanced lipid therapies
Antiplatelet agents
Diabetes therapies for cardiovascular risk reduction
As quoted in the above article: “Awaiting myocardial infarction, stroke, cardiovascular death to qualify for advanced secondary prevention therapies is both unnecessary and Darwinian because some patients will die before qualifying for these advanced therapies.”
Deep Dive
What is a CAC CT Scan?
It’s a non-contrast computed tomography (CT) scan using MDCT (previously EBT) to scan the chest with high resolution gated imaging to search for and quantify the presence of coronary artery calcium (CAC) deposits.
How Does a CAC Test Help with Risk Assessment?
CAC provides independent incremental information for predicting all-cause mortality in addition to traditional risk factors by the extent and the number of vascular territories involved (1 vs 3 vessel involvement, for instance) Long-Term Prognosis Associated With Coronary Calcification: Observations From a Registry of 25,253 Patients
Dr. Arthur Agatston (The Agatston Center) first described this technology as an effective tool for cardiovascular risk assessment in 1990 (Quantification of coronary artery calcium using ultrafast computed tomography - ScienceDirect).
Who Should Obtain a CAC Test?
Testing for the presence of coronary artery calcification by way of a non-contrast CT scan with Agatston score is appropriate for adults at intermediate risk as well as low risk individuals with a family history of premature heart disease. It allows for more personalized risk assessment, rather than extrapolating population data composed of risk factors to the individual.
The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines recommends the selective use of CACscoring in primary prevention to aid in the decision-making process regarding statin therapy when there is uncertainty on the part of the clinician or patient.
What Does Calcification Represent?
Coronary artery calcification (CAC) is pathognomonic (specifically characteristic) for coronary artery atherosclerosis (plaquing). We’ve known this for > 100 years when rabbit studies were performed Nikolaj Nikolajewitsch Anitschkow (1885-1964) established the cholesterol-fed rabbit as a model for atherosclerosis research
Calcification occurs even at early stages of plaque development
Calcification represents about 20% of the overall plaque volume
Calcification is the byproduct of plaque inflammation
Where calcification exists, we know that inflammation has existed and is likely ongoing
Just like in bone remodeling, calcification is a dynamic process
The higher the degree of calcification in the coronary arteries, the higher the degree of inflamed atherosclerotic plaque
Those with the highest amount coronary artery calcification are at the greatest near term (10 year) risk for atherosclerotic cardiovascular disease events (MI, stroke, CABG, stents, etc)
Anyone < 50 years of age with CAC > 0 automatically has a high lifetime risk or high trajectory for succumbing to an ASCVD event
Those with the highest risk by virtue of coronary calcium score, stand to have the greatest benefits to risk factor modification, lipid lowering therapies and possibly aspirin
Calcification is not necessarily the target of our therapy - the inflamed plaque residing adjacent to it is
Yes, statins and other lipid lowering therapy will increase CAC score (about 20-30%) because they increase the “density” of the plaque, which is part of the Agatston score, as “plaque stabilization” ensues.
Plaque stabilization is a good thing
If CAC progresses > 20-30% despite aggressive lipid lowering therapy, it’s possible the disease is progressing
How is a CAC Score Derived?
The CT scan has a software package that identifies calcification based upon Hounsfield Units (HU).
Calcification > 130 HU is “captured”. Calcification < 130 HU is not captured.
The CT scan image is divided into “voxels”
The density and area of the calcified component within each voxel is measured and given an “Agatston score”
HU 130-199: 1
HU 200-299: 2
HU 300-399: 3
HU > 400: 4
For each “lesion” the calcium score is the summation of the scores within all voxels belonging to that lesion
The total calcium score is the summation of all of the lesions along the entire coronary artery “tree”
CAC Agatston Scoring Reference
0: None
1-10: Minimal
11-100: Mild
101-300: Moderate
> 300: Severe
How do the CAC Scores Translate into Risk?
There are 2 significant risk assessments to which CAC scores inform upon:
“Near term” or 10 year risk: demonstrated by the total CAC number:
Coronary Artery Calcium Scanning: Past, Present, and Future | JACC: Cardiovascular Imaging and When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry
CAC = 0: 1.1-1.7%
CAC = 1-100: 2.3-5.9%
CAC = 101-400: 12.8-16.4%
CAC = > 300: 9% over 4 years
CAC = 401-1000: 22.5–28.6%
CAC = > 1000: 37%
“Lifetime” or 30 year risk: percentile rank when compared against others of the same age, gender and race
MESA (Multi-Ethnic Study of Atherosclerosis) Calcium Calculator is preferred
10 Year Risk:
The power of 0: A score of 0 imparts a very low risk, with a 10 year event rate of 1.1-1.7% (Interplay of Coronary Artery Calcification and Traditional Risk Factors for the Prediction of All-Cause Mortality in Asymptomatic Individuals | Circulation: Cardiovascular Imaging). CAC testing can therefore prevent the overtreatment in up to 50% of individuals where traditional risk calculators would have otherwise directed towards treatment with statin therapy.
Those with 2 consecutive "0" scores have the lowest risk.
The Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring - ScienceDirect in this paper demonstrated that there is a reduction in Major Adverse Cardiovascular Events (MACE) in patients with CAC, but not in those without CAC. The NNT (Number Needed to Treat) for CAC > 100 is 12. That means you only need to treat 12 people with a CAC > 100 to prevent a single event. A good NNT is generally ~50. Conversely, the NNT for CAC 0 is 3571!
But - and this is critical - that’s over a 10 year period. We’re talking about near term risk here. This is not an excuse to sleep on the FH patient (Hiding in Plain Sight - Familial Hypercholesterolemia), for instance! If lifetime (30 year) risk is high, guidelines recommend early intervention.
The time-frame for repeat CAC screening has been recommended as follows by The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction - Journal of Clinical Lipidology:
Low risk (<5% 10 year risk): 5-7 years
Borderline to intermediate risk (5-19.9% 10 year risk): 3-5 years
High risk or diabetes: 3 years
Score 1-100: In MESA, individuals with a calculated 10 year risk of a cardiovascular event between 5 and 7.5% (borderline for considering a statin) with any CAC score > 0 was associated with a risk > 7.5% (above the threshold for statin benefit). Therefore, the presence of any calcification in this group may justify treatment with lipid lowering therapy using a statin (Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis).
Even those with minimal CAC (1-10), the event rate begins to pick up, with a 1.4 times increased risk of death from any cause, compared with a CAC score of 0. (A long-term, competing risk analysis in the Coronary Artery Calcium Consortium - ScienceDirect)
Score > 100: This is considered to be a "coronary artery disease risk equivalent", meaning your 10-year risk of a future cardiovascular event is equivalent to someone who has already suffered an event (secondary prevention). A target LDL-C < 70 mg/dL or even lower (< 55 mg/dL) is recommended by some guidelines (Dyslipidemia, Coronary Artery Calcium, and Incident Atherosclerotic Cardiovascular Disease | Circulation) and experts Coronary Artery Calcium Score as a Graded Decision Tool. Symptomatic individuals ought to be considered for nuclear stress imaging.
Score > 300: This represents severely elevated cardiovascular risk. In the large multinational CONFIRM registry, CAC scores > 300 imparts equivalent risk for ASCVD event as heart attack survivors, which was 9% over 4 years (When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry) and 10 fold higher than those with CAC = 0 Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups | NEJM.
At this level, experts recommend utilization of secondary prevention measures in such patients. This includes high intensity lipid lowering therapy aimed at > 50% LDL-C reduction from baseline and threshold LDL-C < 55 mg/dL (< 40 mg/dL for "extreme" risk patients, defined as secondary prevention with multiple additional risk factors), nonHDL-C < 80 mg/dL 2022 American College of Cardiology Expert Consensus Statement ). NonHDL-C should be employed for any patient with triglycerides (TG) > 150 mg/dL (See Atherogenic Triad). Apolipoprotein B or "Apo B" is considered to be at least an equivalent or superior biomarker to either LDL- C or nonHDL-C and should be treated to a level < 60 mg/dL (< 50 mg/dL in extreme risk patients) by many experts See What's Your ApoB? A Practical Approach to Lipid Management).
Score > 400: Very high risk. Very high annual event rate of 4.8%. Up to 35% of such individuals have been found to have an abnormal stress test, despite the absence of symptoms. Some have therefore suggested stress testing in such patients, though this is controversial (The incremental value of coronary artery calcium scores to myocardial single photon emission computer tomography in risk assessment).
The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction does not recommend stress testing (Class III - potentially harmful).
However, a "State-Of-The-Art Paper" Coronary Artery Calcium Scanning: Past, Present, and Future | JACC: Cardiovascular Imaging references the 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults, which gives myocardial perfusion imaging in asymptomatic patients with CAC > 400 a Class IIb recommendation (may be considered), due to the high incidence of abnormal nuclear stress testing (35%) in such patients.
Based upon these divergent recommendations, an individualized patient centered discussion seems reasonable.
Lifetime Risk:
MESA Percentile Rank: This is derived from the National Heart Lung and Blood Institute's MESA (Multi-Ethnic Study of Atherosclerosis) database Calcium Calculator. This is a percentile that compares you to other individuals of the same age, gender and race.
> 75th: High risk, regardless of CAC score. It represents premature coronary artery disease. Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women
> 90th: Very high risk with an annual event rate of 6.5%.
Additional Risk Beyond the CAC Score Itself:
Diffuse CAC
For a given CAC score, a more diffuse CAC distribution (2 or 3 coronary involvement vs. 1 coronary) is associated with higher risk (The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction).
Left Main CAC
“For a given CAC score, greater left main CAC predicts risk beyond the total CAC score, particularly when > 25% of the total score…and should be viewed as an additional factor favoring more aggressive preventive pharmacotherapy.” (The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction)
Abdominal Aortic Calcification:
Scores > 1000 have similar risk of ASCVD as those with CAC score > 300, meaning secondary prevention (Association of Abdominal Aorta Calcium and Coronary Artery Calcium with Incident Cardiovascular and Coronary Heart Disease Events in Black and White Middle‐Aged People: The Coronary Artery Risk Development in Young Adults Study).
Does Calcification Mean I Have a Major Blockage?
No. Although calcification increases with age, it has been developing for several decades.
While CAC is essentially definitive for the detection of coronary atherosclerosis, it does not always indicate that there is a blockage in a major artery large enough to create a drop in blood flow to the heart muscle tissue (ischemia). A 70% blockage in the diameter of a major coronary artery is usually required to cause one to have symptoms of chest discomfort, tightness, shortness of breath or other limiting symptoms with exertion (angina). A 90% diameter blockage may cause such symptoms at rest.
“If I don’t have a major blockage, then I won’t have a heart attack, right?”
Wrong.
While major blockages are important to diagnose, studies have shown that younger patients admitted to the hospital for their "first heart attack" were the result of rupture from a "nonobstructive" plaque (< 70%). The majority of such patients would not have met criteria for placement on prevention therapy based upon conventional risk calculators lacking coronary artery calcium score input (Preventing myocardial infarction in the young adult in the first place: how do the national cholesterol education panel iii guidelines perform? - ScienceDirect.) Presently there is no reliable clinical test for detecting such "vulnerable plaque". However, coronary artery calcium score testing, when added to conventional risk calculators, has been shown to improve our ability to "reclassify” an individual's risk for ASCVD events better than any other available screening tool, with a better NRI (Net Reclassification Index) and C-statistic (Receiver Operator Curve) than other commonly used biomarkers (such as hs-CRP) (Coronary Artery Calcium Scores: Current Thinking and Clinical Applications - PMC), to include diabetics (Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy).
Do I need to take Aspirin?
MESA demonstrates that in those free of diabetes, a CAC = 0 predicted net harm with aspirin. Conversely, a CAC > 100 predicted net benefit, regardless of risk factors. Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019 | Circulation
The Society of Cardiac CT recommends consideration of aspirin for all with CAC >100 Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019 | Circulation.
Can CAC inform on other Cardiometabolic Risk?
A CAC score >220 (Role of Coronary Artery Calcium for Stratifying Cardiovascular Risk in Adults With Hypertension) may warrant more aggressive personalized blood pressure goals, as it identifies patients with "SPRINT-equivalent risk." (SPRINT Trial: A Randomized Trial of Intensive versus Standard Blood-Pressure Control | NEJM)
This “Viewpoint” paper published in JACC Journals (Coronary Artery Calcium Score as a Graded Decision Tool) advises: “Patients with CAC >300 (and possibly >100) and elevated SBP should be more aggressively treated for a SBP in the range of 120.
Stronger consideration should also be given to adding a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists in these higher risk patients.” Coronary Artery Calcium for the Allocation of GLP-1RA for Primary Prevention of Atherosclerotic Cardiovascular Disease, Cardiac Computed Tomography for Personalized Management of Patients With Type 2 Diabetes Mellitus | Circulation: Cardiovascular Imaging).
How Often Should I Repeat a CAC Screening?
In general, you should repeat any test only if it is likely to alter management. Some guidance is provided by the The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction:
CAC = 0:
Low risk (<5% 10 year risk): 5-7 years
Borderline to intermediate risk (5-19.9% 10 year risk): 3-5 years
High risk or diabetes: 3 years
CAC 1-99: (Mild)
It may be reasonable to repeat coronary artery calcium scoring in 3-5 years if the results might change treatment decisions (Class IIb recommendation).
CAC 100-299 (Moderate)
Repeat in 3 years to assess for accelerated progression, which may favor more aggressive lipid lowering (Class IIb recommendation):
>20-25% per year and/or
An increase to >300
High Risk Percentile Rank:
It may be reasonable to repeat coronary artery calcium scoring in 3-5 years if the results might change treatment decisions (Class IIb recommendation).
Do I need to see a specialist?
As with all such studies we recommend discussing these results with your primary care or ordering provider. For expert advice consider referral to a preventive cardiologist, cardiometabolic specialist clinical lipidologist.
Future Directions:
The Agatston score has not changed since inception.
As technology improves and radiation dosing and costs have come down, potential avenues for further exploration include:
Subthreshold CAC: What about CAC that is visible to the reader but < 130 HU
Some experts recommend repeating CAC testing in 1 year
Looking beyond CAC on CT (Coronary Artery Calcium Scoring: Current Status and Future Directions | RadioGraphics)
Epicardial fat content
“Fatty heart” content
Assessing fatty liver on CAC screens (some of the liver is seen on these scans)
Cardiac CT angiography replacing CAC as screening test of choice for subclinical coronary atherosclerosis?
This provocative paper: Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort screened a general population and followed them over 3.5 years:
46% with at least some disease
10% obstructive disease
10% extensive disease
5% obstructive and extensive disease
Risk of heart attack and death tracked with disease burden
A pitiful 22% of patients were on lipid lowering therapy!
What about CTA for assessing plaque composition?
Cleerly , according to their website “uses proprietary and FDA-cleared machine learning algorithms to non-invasively analyze atherosclerosis (plaque) and stenosis using standard CCTA studies.”
The role of Artificial Intelligence to enhance CAC scoring through automated scoring or virtual reconstruction on virtually any Chest CT.
Additional References of Interest
Q & A Forum
If you have any questions or constructive feedback, we aim to address these here.
