What percentage of individuals with a zero coronary calcium (CAC) score have atherosclerotic plaque detected on coronary CT angiography?

Atherosclerosis Detection in Patients with Zero CAC Score

Among symptomatic patients with a zero coronary artery calcium (CAC) score, approximately 13-17% have atherosclerotic plaque detected on coronary CT angiography (CCTA), with 3.5% having ≥50% stenosis and 1.4% having ≥70% stenosis. 1

Prevalence Data from Major Studies

The most robust evidence comes from the large, multicenter CONFIRM registry, which provides the highest-quality data for symptomatic populations:

• In 10,037 symptomatic patients without known CAD who had CAC = 0, CCTA revealed:

  • Mild, nonobstructive CAD in 13% 1
  • Stenosis ≥50% in 3.5% 1
  • Stenosis ≥70% in 1.4% 1

• Additional research studies in symptomatic populations show variable rates:

  • 8.9% prevalence of atherosclerotic plaque (with 32.3% of those having obstructive disease) 2
  • 9.3% frequency of atherosclerotic plaque (with 47% having significant coronary obstructions >50%) 3
  • 17.4% detection of noncalcified plaques (with 2.1% having significant stenosis) 4

Asymptomatic vs. Symptomatic Populations

The distinction between asymptomatic and symptomatic patients is critical for interpreting these numbers:

• In asymptomatic individuals with CAC = 0, the prevalence is lower:

  • 7% had noncalcified plaque (6% non-obstructive, 1% obstructive) 5
  • The prognosis remains excellent with negligible future risk during median 22-month follow-up 5

• In symptomatic patients, the false-negative rate is substantially higher:

  • Small single-center studies reported 0-39% of symptomatic patients with CAC = 0 had perfusion defects or high-grade stenosis 1
  • The CORE64 study found 19% of symptomatic patients with CAC = 0 had at least one vessel with ≥50% stenosis 6

Plaque Composition and Characteristics

The atherosclerotic burden in patients with zero CAC is predominantly noncalcified:

• Among patients with CAC = 0 who have plaque, 97.9% of total plaque volume is noncalcified 7
• These noncalcified plaques are completely missed by calcium scoring alone 7
• The left anterior descending artery is the most frequently affected vessel (38.2% of plaques) 4
• Proximal segments harbor 50% of plaques, mid-segments 42.7%, and distal segments 7.3% 4

Risk Factors Associated with Plaque Despite Zero CAC

Specific clinical characteristics increase the likelihood of finding atherosclerosis despite CAC = 0:

• Age is independently associated with presence of noncalcified plaque 5
• Male gender significantly increases risk 5
• Diabetes mellitus is independently associated with plaque presence 5, 4
• Hypertension is a significant risk factor in both genders 5, 4
• Dyslipidemia independently predicts noncalcified plaque 5
• Non-obese individuals paradoxically had higher frequency of plaques (90.6% vs 73.9%, OR 3.4) 3
• Alcohol consumption was associated with higher plaque frequency (55.9% vs 34.8%, OR 3.4) 3

Age-Specific Considerations

Younger patients are disproportionately affected by the limitations of calcium scoring:

• Documentation of obstructive CAD without CAC occurs more often in younger patients in whom atherosclerotic plaque has not advanced to the stage of calcification 1
• In patients <40 years with obstructive CAD, 58% had CAC = 0, compared to only 9% among those aged 60-69 years 6

Clinical Implications and Pitfalls

Common pitfalls to avoid:

• Never assume CAC = 0 excludes coronary disease in symptomatic patients – the false-negative rate is too high (3.5-19% depending on the study) 1, 6
• Do not use CAC scoring as a surrogate for anatomical disease detection in symptomatic individuals – it was designed for risk stratification in asymptomatic populations 1
• Recognize that calcium scoring has poor specificity for diagnosing obstructive CAD due to the modest relationship between calcification and luminal obstruction 8
• In symptomatic patients with CAC = 0 and high clinical suspicion, proceed directly to CCTA or functional testing rather than relying on the calcium score to exclude disease 6

Prognostic Context

Despite the presence of plaque in some patients with CAC = 0, the overall prognosis remains excellent:

• Annual mortality and MI risk remains below 1% for over 15 years in patients with CACS = 0 6
• In asymptomatic patients with CAC = 0, only 0.47% experienced adverse cardiovascular events during 50-month follow-up 6
• The excellent prognosis holds even in high-risk populations when CAC = 0 6