What is the coronary artery calcium (CAC) score system and how is it used to assess cardiovascular disease risk in asymptomatic individuals?

Coronary Artery Calcium Score System

What the CAC Score Measures

The coronary artery calcium (CAC) score quantifies calcified atherosclerotic plaque in the coronary arteries using electrocardiogram-gated multidetector CT scanning, serving as a direct marker of total atherosclerotic burden and vascular age. 1

• The scan uses relatively low radiation exposure (0.37-1.5 mSv), comparable to or less than screening mammography 1, 2
• Coronary calcifications occur exclusively in atherosclerotic lesions of the intimal layer, making CAC a definitive marker of atherosclerosis presence 2
• CAC represents approximately 20% of total atherosclerotic burden, as not all plaques contain calcium 1

The Agatston Scoring System

The Agatston score is the universally accepted scoring method in clinical practice and research. 1

• A calcific lesion is defined as having CT density >130 Hounsfield units and area >1 mm² 1, 2
• Each lesion receives a weighting factor of 1-4 based on CT density 1
• The lesion score equals area multiplied by the weighting factor 1
• Total CAC score is the sum of all individual lesion scores across all coronary arteries 1
• Scores can be expressed as age-, sex-, and race-adjusted percentiles (white, Chinese, Black, Hispanic populations) 1

Risk Categories and Prognostic Significance

CAC Score = 0: "The Power of Zero"

A zero calcium score confers excellent prognosis with <1% annual risk of cardiac death or myocardial infarction, even in patients classified as high-risk by traditional risk factors. 1, 3

• Among asymptomatic patients with CAC = 0, only 0.47% experienced adverse cardiovascular events at 50-month follow-up 1
• Mortality remains <1% yearly for >15 years in CAC = 0 patients 1
• Even diabetic patients with CAC = 0 have similarly low 5-year mortality as non-diabetic CAC = 0 patients 1
• Statin therapy can generally be deferred unless diabetes, active smoking, family history of premature CAD, or chronic inflammatory conditions are present 3

CAC Score 1-99: Mild Disease

Any detectable calcium (score >0) indicates presence of atherosclerosis and incrementally increases cardiovascular risk above zero. 2, 3

• Statin therapy is favored, especially for patients aged >55 years 3
• 10-year ASCVD event rates range from 3.8% (ages 45-54) to 14.3% (ages 75-85) 3
• Observed event rate is 10.4% in this category 3

CAC Score 100-399: Moderate Disease

Moderate calcium burden substantially increases cardiovascular risk and warrants aggressive preventive therapy. 1

• Statin therapy is strongly recommended when CAC ≥100 or ≥75th percentile for age/sex 3
• Event rate exceeds 20 events per 1,000 person-years 3
• Number needed to treat with statins for 5 years is 42 3

CAC Score ≥400: Severe Disease

Severe coronary calcification confers high cardiovascular risk and may warrant screening for clinically silent ischemia. 1

• ACC/AHA 2010 guidelines recommend screening for silent ischemia when CACS >400 1
• Cardiovascular risk increases exponentially at scores >400 1

CAC Score >1000: Very High Risk

One-third of individuals with scores >1000 will experience a cardiovascular event within 3 years. 4

Vessel Distribution and Location

The anatomic distribution of calcium provides critical prognostic information beyond the absolute score. 1

• Left main coronary artery (LMCA) calcification carries 20-40% higher mortality risk compared to calcium in other vessels 1, 5
• Annual risk-adjusted mortality reaches 7.71% when LMCA CACS >400 1
• Multi-vessel disease (2-vessel, 3-vessel, or 3-vessel + LMCA) substantially increases all-cause mortality beyond the total score alone 1
• Greater numbers of calcified coronary arteries improve prediction of CAD events 1

Clinical Applications and Appropriate Use

Primary Indication: Risk Stratification in Asymptomatic Patients

CAC scoring is most valuable for asymptomatic adults aged 40-75 years with intermediate (7.5-20%) or borderline (5-7.5%) 10-year ASCVD risk when decisions about preventive therapy are uncertain. 1, 2, 3

• Nearly one-fifth of US adults aged 45-79 years fall into the intermediate-risk category 1
• CAC scoring improves risk prediction with net reclassification index of 25% and increases C-statistic from 0.76 to 0.81 3
• Intermediate-risk patients without CAC can be reclassified to lower-risk, potentially avoiding statin therapy 1, 2
• Selected low-risk adults with family history of premature CAD may also be considered 2, 3

Younger Adults

CAC scoring is recommended for younger adults (30-49 years) with risk factors, where CAC >0 increases CAD events 3-12 fold. 3

• CAC >100 confers 10-fold higher mortality in this age group 3

Contraindications

CAC scoring should NOT be used in symptomatic patients to exclude obstructive coronary artery disease. 2, 3

• 19% of symptomatic patients with CAC = 0 had ≥50% stenosis in the CORE64 study 3
• 3.5% of symptomatic patients with CAC = 0 had ≥50% stenosis and 1.4% had ≥70% stenosis 2
• CAC has poor specificity for diagnosing obstructive CAD due to modest relationship between calcification and luminal obstruction 2

CAC scoring is not appropriate for truly low-risk asymptomatic patients (<5% 10-year ASCVD risk) because it does not provide actionable information. 2

• Men under 40 and women under 50 years have low prevalence of calcification 1
• Insurance often denies coverage for inappropriate indications 2

Critical Limitations

CAC scoring should be viewed primarily as a marker of atherosclerotic burden, not stenosis severity. 1, 2

• Lumen patency is often preserved by vascular remodeling with limited correlation between calcium and luminal narrowing 1
• CAC cannot detect non-calcified atherosclerotic plaques present in earlier disease stages 2
• The score represents only 20% of total atherosclerotic plaque burden 1, 5

Follow-Up and Repeat Scanning

Repeat CAC scanning is not recommended sooner than 3-5 years unless initial management decisions were uncertain. 5

• Annual cardiovascular risk assessment should monitor lipids, blood pressure, glucose metabolism, and medication adherence 5

Common Pitfalls to Avoid

• Do not dismiss low scores (e.g., CAC = 7) as insignificant—any measurable calcium indicates atherosclerosis and incremental risk 2, 5
• Do not assume CAC score correlates with stenosis severity—it indicates plaque burden, not flow-limiting disease 2, 5
• Do not use CAC = 0 to exclude obstructive CAD in symptomatic patients—up to 19% may still have significant stenosis 3
• Do not order CAC scoring in low-risk asymptomatic patients—the test yield is extremely low and results rarely change management 2