What does a calcium score of 0 on a computed tomography (CT) scan indicate for coronary artery disease risk?

Coronary Artery Calcium Score of Zero: Interpretation and Clinical Significance

A coronary artery calcium (CAC) score of zero indicates an excellent prognosis with a very low risk of cardiac events in the short to medium term, but does not completely exclude the presence of coronary artery disease, especially in symptomatic patients.

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 1
• In asymptomatic individuals, a CAC score of zero indicates an extremely low likelihood of cardiovascular events in the next 5 years 2
• The absence of coronary calcification at baseline is associated with lower rates of clinical events compared to those with measurable coronary artery calcification 1
• A zero CAC score represents "the power of zero" - patients have a highly favorable prognosis with annual mortality rates <0.5% 1

Limitations of Zero CAC Score

• In symptomatic patients, a zero CAC score does not completely exclude obstructive coronary artery disease, as noncontrast CT does not detect noncalcified atherosclerotic plaque 1
• In the CORE64 study, 19% of symptomatic patients with CAC=0 had at least one vessel with ≥50% stenosis 1
• 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 1
• Young adults are particularly prone to having noncalcified plaques despite zero calcium scores 3

Risk Stratification Based on CAC Score

• CAC scoring is quantified using electrocardiogram-gated multidetector CT scan, with radiation exposure comparable to screening mammography 1
• 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 1
• Traditional CAC score categories include:
  • Zero (no identifiable plaque)
  • 1-99 (mild plaque burden)
  • 100-399 (moderate plaque burden)
  • ≥400 (severe plaque burden) 1

Clinical Recommendations for Patients with Zero CAC Score

• For asymptomatic individuals with zero CAC score, reassurance is appropriate as the risk of cardiovascular events is very low 1
• 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 1
• Recent technical improvements can detect subtle calcifications in patients with official Agatston scores of zero by reducing size and density thresholds, which may improve risk stratification 4
• The 2018 ACC/AHA Cholesterol Guidelines endorse the use of CAC scores in asymptomatic, intermediate-risk individuals where the decision to initiate statin therapy is uncertain 5

Special Considerations

• Risk factors such as age, male gender, hypertension, diabetes, and elevated LDL cholesterol are independent predictors of obstructive CAD even in patients with zero CAC scores 3
• Noncalcified plaques associated with cardiac events despite zero CAC scores tend to have lower CT density numbers, higher remodeling indexes, and worse degrees of stenosis 3
• In patients with symptoms suggestive of acute coronary syndrome and low TIMI risk scores, approximately 2.1% with CAC=0 may still have significant CAD (>50% stenosis) 6

Algorithmic Approach to Zero CAC Score

1. For asymptomatic individuals with zero CAC score:

   • Provide reassurance about low cardiovascular risk 1
   • Continue standard preventive measures based on other risk factors 1

2. For symptomatic individuals with zero CAC score:

   • Consider non-atherosclerotic causes of symptoms 1
   • Evaluate for presence of risk factors (age, male gender, hypertension, diabetes, elevated LDL) 3
   • Consider additional testing such as CT coronary angiography if clinical suspicion remains high, especially in younger patients 1, 3

3. For follow-up of patients with zero CAC score:

   • Repeat testing is generally not needed within 5 years for asymptomatic individuals 1
   • For symptomatic patients with persistent symptoms despite zero CAC score, consider functional testing or CT coronary angiography 1