Coronary Calcium Emerges as Key Risk Marker in Low CV Risk Patients, Latest AJPC December 2025 Study

This analysis is published in December 2025 in the American Journal of Preventive Cardiology.

These findings suggest that more widespread use of CAC in this population may be warranted to guide clinical management.

Assessing Risk in Low-CV Risk Populations

Coronary artery calcium (CAC) scoring by CT is an established tool for assessing atherosclerotic cardiovascular disease (ASCVD) risk and has been shown to improve prediction when added to the Pooled Cohort Equations (PCE). Current guidelines recommend CAC primarily for individuals with intermediate or select borderline 10-year ASCVD risk to help inform statin therapy decisions. However, its role in low-risk individuals remains uncertain—an important gap, since aggressive risk-factor modification is generally not advised for this group. This study evaluated the relationship between CAC scores and ASCVD/coronary heart disease (CHD) events across the full spectrum of baseline risk, with particular emphasis on low- and borderline-risk populations, and assessed whether adding CAC to the PCE and the new AHA PREVENT equations enhances risk prediction.

Study Overview

This prospective cohort study utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), which recruited 6,814 individuals without known cardiovascular disease across six centers in the United States between 2000–2002. After exclusions, the final study population comprised 6,712 participants.

For this research, 10-year ASCVD risk was estimated using both the PCE and the AHA PREVENT equations. Risk categories were defined as:

• Low risk: <5%.

• Borderline risk: 5% to <7.5%.

• Intermediate risk: 7.5% to <20%.

• High risk: ≥20% risk.

CAC scoring was performed at baseline using the Agatston method via electron-beam or multi-detector CT. Primary outcomes included coronary heart disease (CHD)—fatal or nonfatal myocardial infarction (MI) or resuscitated cardiac arrest—and ASCVD, defined as CHD plus fatal or nonfatal stroke. Enhancements in risk prediction were assessed using Harrell’s C-index and net reclassification improvement (NRI).

Key Findings from the Study:

The study showed that coronary artery calcium was a powerful predictor of ASCVD and CHD events across all baseline risk categories, with particularly important implications for low and borderline-risk patients.

• Event Rates: Participants with any detectable CAC (>0) had markedly higher ASCVD event rates (14.3 vs. 4.1 per 1,000 person-years) compared with those with a score of zero.

• Elevated Risk in Low/Borderline Groups: CAC was strongly associated with increased ASCVD risk among low-risk (HR 1.35) and borderline-risk individuals (HR 1.30). For CHD events alone, risk was even higher in the low-risk group (HR 1.48).

• High Prevalence of CAC: Despite being classified as low risk by traditional equations, 22.1% of low-risk and 46.3% of borderline-risk participants already had measurable CAC.

• Improved Risk Prediction: Adding CAC to the Pooled Cohort Equations significantly enhanced risk discrimination in both low-risk (+0.047 in C-index) and borderline-risk (+0.105) individuals. Similar improvements were observed when CAC was added to the AHA PREVENT equations.

• Strongest Effect in Younger Adults and Men: CAC conferred a greater risk increase and larger predictive improvement among adults under 50 and among men, suggesting underestimation of risk by traditional tools in these groups.

Clinical Inference: Expanding CAC Utilization

Current guidelines narrowly recommend CAC scoring mainly for intermediate and select borderline-risk patients. This study suggests that CAC may be useful in a broader range of individuals, particularly those categorized as low or borderline risk.

For practicing cardiologists, these results provide evidence supporting a shift toward more widespread use of CAC scoring to identify silent atherosclerosis in low-to-borderline risk patients, allowing for more aggressive, early intervention before a major ASCVD event occurs.

Reference: Davis JR, Razavi AC, Ellberg CC, Blaha MJ, Criqui MH, Bhatia HS. Utility of coronary artery calcium scoring in low-risk patients: The Multi-Ethnic Study of Atherosclerosis (MESA). Am J Prev Cardiol. 2025 Oct 13;24:101329. doi: 10.1016/j.ajpc.2025.101329. PMID: 41159137; PMCID: PMC12557561.

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