Coronary Artery Calcium Score of Zero: Interpretation and Clinical Significance

Clinical Significance of Zero CAC Score

A zero CAC score has a high negative predictive value for excluding obstructive coronary artery disease (CAD) and is associated with a good medium-term prognosis, according to the American College of Radiology 1
The absence of coronary calcification at baseline is associated with lower rates of clinical events compared to those with measurable coronary artery calcification, as reported by the American College of Radiology 1
A zero CAC score represents a highly favorable prognosis with annual mortality rates <0.5%, as stated by the Journal of Internal Medicine 2

In symptomatic patients, a zero CAC score does not completely exclude obstructive coronary artery disease, as noncontrast CT does not detect noncalcified atherosclerotic plaque, according to the Journal of Internal Medicine 3, 4
In the CORE64 study, 19% of symptomatic patients with CAC=0 had at least one vessel with ≥50% stenosis, as reported by the Journal of Internal Medicine 4
In the CONFIRM registry, among symptomatic patients with zero CAC score, 13% had nonobstructive disease, 3.5% had ≥50% arterial stenosis, and 1.4% had ≥70% stenosis, according to the American College of Cardiology 5

The Agatston score is the most widely used CAC scoring system, defining calcific lesions as having CT density >130 Hounsfield units and area >1 mm², as stated by the Journal of Internal Medicine 2
Traditional CAC score categories include 1-99 (mild plaque burden), 100-399 (moderate plaque burden), and ≥400 (severe plaque burden), as reported by JACC: Cardiovascular Imaging and the Journal of Internal Medicine 2, 6

For asymptomatic individuals with zero CAC score, reassurance is appropriate as the risk of cardiovascular events is very low, according to JACC: Cardiovascular Imaging 6
For symptomatic patients, a zero CAC score should not be relied upon to exclude CAD, and further evaluation may be warranted depending on clinical presentation, as stated by the Journal of Internal Medicine 4
The American College of Cardiology recommends considering non-atherosclerotic causes of symptoms and evaluating for presence of risk factors in symptomatic individuals with zero CAC score 5, 6

For asymptomatic individuals with zero CAC score, provide reassurance about low cardiovascular risk and continue standard preventive measures based on other risk factors, as recommended by JACC: Cardiovascular Imaging and the Journal of Internal Medicine 2, 6
For symptomatic individuals with zero CAC score, consider additional testing such as CT coronary angiography if clinical suspicion remains high, especially in younger patients, according to the American College of Cardiology and the Journal of Internal Medicine 5

The European Society of Cardiology recommends that asymptomatic individuals with a zero coronary artery calcium (CAC) score do not require further diagnostic testing, as they have a very low likelihood of obstructive coronary artery disease (CAD) 7, 8
Asymptomatic patients with a zero CAC score have an excellent prognosis, with annual cardiovascular event rates less than 0.5%, according to the European Heart Journal 7, 8
The "power of zero" is well-established in asymptomatic populations, with event rates of only 0.8 per 1,000 person-years, as reported in the MESA cohort 9

The American College of Cardiology and American Heart Association guidelines recommend a selective strategy using CAC to guide coronary computed tomography angiography (CCTA) in symptomatic patients, as a zero CAC score does not exclude obstructive CAD 10
A zero CAC score does not exclude obstructive CAD in symptomatic patients, as non-calcified plaque causing obstructive disease cannot be excluded, according to the Journal of Internal Medicine 11
In the CORE64 substudy, 19% of symptomatic patients with a zero CAC score had at least one vessel with ≥50% stenosis, and 20% of occluded vessels had no calcium 11
Obstructive disease is present in 7-38% of symptomatic patients with a zero CAC score, highlighting the importance of considering CCTA in these patients 11

The European Society of Cardiology guidelines note that age significantly impacts the reliability of a zero CAC score for excluding obstructive CAD, with younger patients being more likely to have non-calcified obstructive disease 7, 8
In younger patients (<40 years), obstructive CAD is more likely to be non-calcified, with 58% of those with obstructive CAD having a zero CAC score, compared to only 9% among those aged 60-69 years 7, 8

For symptomatic patients with a zero CAC score, the American College of Cardiology and American Heart Association guidelines recommend assessing symptom characteristics and calculating pretest probability using contemporary models, such as the RF-CL model 10
If intermediate-high pretest probability or age <40 years with concerning symptoms, proceed with CCTA, as recommended by the Journal of Internal Medicine and the American College of Cardiology 11, 10

Annual mortality and MI risk remains below 1% for over 15 years in patients with a coronary artery calcium score (CACS) of 0, even among those classified as high risk by traditional Framingham scoring 12
In a systematic review of 13 studies involving 71,595 asymptomatic patients, only 0.47% experienced adverse cardiovascular events during 50-month follow-up among those with CACS = 0 12
The mortality risk for elderly men with zero CCTA score is lower than for patients with no cardiovascular risk factors or those classified as low risk by traditional scoring systems 12

The European Society of Cardiology emphasizes that a normal CCTA almost completely rules out obstructive CAD with a very low negative post-test likelihood of 2% in appropriate patient populations 13, 14