Coronary artery calcium (CAC) scoring has emerged as one of the most important imaging biomarkers for cardiovascular risk assessment by providing a quantitative measure of cumulative coronary atherosclerotic burden. Derived from non-contrast cardiac computed tomography using the Agatston method, CAC offers standardized, reproducible, and prognostically robust information that extends beyond traditional risk factors. A large body of evidence demonstrates a graded relationship between increasing CAC scores and adverse cardiovascular outcomes, while a score of zero is associated with low short to intermediate term event risk, although not complete absence of disease. In contemporary cardiology practice, CAC plays a critical role not only in risk stratification but also in therapeutic decision-making, particularly in individuals with borderline or intermediate estimated risk where treatment uncertainty exists. CAC-guided approaches can inform statin initiation, preventive therapy intensity, and, in selected cases, aspirin allocation, while also serving as a potential gatekeeper before coronary computed tomographic angiography (CCTA). However, several important limitations remain, including inability to detect non-calcified plaque, challenges in interpreting serial progression, and reduced CCTA specificity in patients with very high calcium burden due to blooming artifacts. Advances in imaging technology, artificial intelligence–based quantification, and multiparametric plaque assessment are expected to further enhance the clinical utility of CAC in the future. This review provides a comprehensive, clinically oriented synthesis of the biological mechanisms, technical principles, prognostic significance, and practical applications of CAC scoring, with particular emphasis on its integration with CCTA and its role in real-world decision pathways.

• Coronary artery calcium scoring

• Cardiovascular risk stratification

• Coronary computed tomographic angiography

• Primary prevention

• Atherosclerotic plaque burden

SAH?N MM, KALCIK M, SARIHAN A, YILMAZ MM, KARAARSLAN O, et al. (2026) Clinical Applications of Coronary Artery Calcium Scoring in Cardiovascular Risk Assessment. J Radiol Radiat Ther 14(1): 1118.

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide, reflecting the cumulative burden of atherosclerotic plaque formation within the coronary arterial tree [1]. Despite substantial advances in preventive cardiology, risk stratification based solely on traditional cardiovascular risk factors remains imperfect, particularly among individuals classified as having borderline or intermediate risk [1,2]. Coronary artery calcium (CAC) scoring, derived from non-contrast cardiac computed tomography (CT), provides a quantitative measure of calcified atherosclerotic plaque burden. Since the introduction of the Agatston method, CAC has become a standardized, reproducible, and widely accessible biomarker of cumulative coronary atherosclerosis [3,4]. Unlike functional testing, which reflects inducible ischemia, CAC reflects the anatomical presence of coronary atherosclerosis and therefore captures subclinical disease before the development of flow-limiting stenosis [5,6]. Large observational cohorts have consistently demonstrated a graded association between increasing CAC scores and the risk of myocardial infarction, cardiovascular mortality, and all-cause mortality [1]. Importantly, a CAC score of zero is associated with a very low short- to intermediate-term event rate in asymptomatic and selected symptomatic populations, a concept often referred to as the “power of zero” [7]. However, the absence of calcification does not fully exclude non-calcified plaque or future risk, particularly in younger individuals and those with high-risk clinical features [8]. Therefore, CAC should be interpreted within an appropriate clinical context rather than as an isolated diagnostic determinant. Beyond risk prediction, CAC scoring has gained increasing relevance in therapeutic decision-making. Contemporary cholesterol management guidelines endorse CAC assessment to refine statin allocation when treatment decisions remain uncertain after traditional risk estimation [2]. In daily cardiology practice, CAC may also function as a gatekeeper before coronary CT angiography (CCTA) in selected patients, potentially reducing unnecessary downstream testing while preserving diagnostic safety [3,5]. Despite advances in CCTA-based plaque characterization and functional imaging techniques, CAC remains uniquely positioned among noninvasive imaging biomarkers as a marker of cumulative atherosclerotic exposure. Its strengths include standardization, reproducibility, prognostic robustness, and relative cost effectiveness. Nevertheless, important questions persist regarding optimal thresholds, integration with age- and sex-specific percentiles, management of very high scores, and the role of serial scanning. In addition, uncertainty remains regarding the optimal integration of CAC into contemporary clinical pathways, particularly in relation to CCTA utilization and individualized preventive decision making. The aim of this review is to provide a comprehensive, clinically oriented synthesis of the biological basis, technical aspects, prognostic implications, and practical applications of CAC scoring in contemporary cardiology. Particular emphasis will be placed on its integration with CCTA and its role in real-world decision-making pathways. In addition, emerging evidence supports more individualized interpretation strategies that extend beyond absolute CAC thresholds alone.

This study was conducted as a narrative review aimed at synthesizing contemporary evidence regarding CAC scoring and its clinical integration with CCTA. Literature was identified through searches of PubMed, MEDLINE, and Google Scholar databases focusing on publications from 2000 to 2026, with emphasis on major cohort studies, randomized trials, meta-analyses, and contemporary clinical guidelines. Key search terms included “coronary artery calcium,” “Agatston score,” “CCTA,” “risk stratification,” “primary prevention,” and “chest pain,” used individually and in combination. Additional references were identified through manual review of citation lists from relevant publications and landmark articles in the field. Studies were prioritized based on clinical relevance, methodological rigor, sample size, and potential impact on contemporary clinical practice. Particular emphasis was placed on major society guidelines, large prospective cohort studies, and investigations addressing practical clinical decision-making. The objective was not to perform a systematic meta-analysis but to provide a clinically oriented synthesis of the most influential and relevant evidence.

Biology of Coronary Calcification

Coronary calcification is now widely recognized not as a passive degenerative phenomenon but as an actively regulated biological process occurring within the atherosclerotic plaque [4,5]. Vascular smooth muscle cells undergo osteogenic differentiation under inflammatory and oxidative stimuli, expressing bone-associated proteins and contributing to calcium deposition within the extracellular matrix. This process parallels mechanisms observed in skeletal mineralization. Two distinct forms of calcification are typically described: microcalcification and macrocalcification. Microcalcifications, often below the spatial resolution of conventional CT imaging, are associated with active inflammation and may contribute to plaque vulnerability by increasing local mechanical stress. In contrast, larger, confluent macrocalcifications generally reflect more advanced stages of plaque evolution and, in some contexts, relative plaque stabilization [5]. However, overall CAC burden reflects cumulative plaque exposure rather than acute plaque instability. Importantly, CAC quantification does not directly assess non-calcified lipid-rich plaque, which may remain clinically relevant, particularly in patients with low or zero CAC scores (8). CAC should therefore be understood as a surrogate for total atherosclerotic burden rather than as a comprehensive plaque characterization tool.

Measurement Principles

The Agatston score remains the most widely used method for quantifying coronary calcium. It is calculated by identifying lesions with attenuation ≥130 Hounsfield units across at least three contiguous pixels and weighting lesion area by peak density [3,4]. The final score represents the sum of weighted lesions across all coronary arteries.Alternative metrics, including calcium volume and mass scores, have been proposed to improve reproducibility by reducing density weighting variability. Although these measures may offer theoretical advantages in longitudinal studies, the Agatston score remains the dominant clinical standard due to extensive validation and prognostic evidence [1,3]. Reproducibility of CAC scoring is generally high, particularly with standardized acquisition protocols and contemporary multidetector CT systems. Inter-scan variability remains an important consideration, especially in serial assessments, and may be influenced by technical parameters such as slice thickness, reconstruction algorithm, and cardiac motion. Modern scanners with prospective electrocardiography (ECG) gating and optimized acquisition protocols have reduced radiation exposure while maintaining measurement reliability [3].

CAC and CCTA: Technical Integration

In clinical workflows, a non-contrast CAC scan is often performed prior to CCTA. This approach provides an estimate of baseline anatomical risk and informs the feasibility of contrast-enhanced coronary imaging [3,5]. Very high CAC burdens may reduce CCTA interpretability due to blooming artifacts, potentially leading to overestimation of luminal stenosis severity. Technical factors such as heart rate control, slice collimation, kernel selection, and reconstruction techniques influence both calcium quantification and downstream CCTA accuracy. With contemporary scanners, radiation exposure for a dedicated CAC scan is typically low and can often be achieved at sub-millisievert levels [3]. From a practical standpoint, CAC serves two complementary roles in relation to CCTA: first, as a gatekeeper that may obviate further testing in low-risk individuals with CAC = 0; and second, as a contextual risk marker that enhances interpretation of anatomical stenosis severity when CCTA is performed. These interactions highlight the importance of interpreting CAC within the broader clinical context rather than as an isolated technical parameter.

Role in Asymptomatic Patients

In asymptomatic adults, CAC primarily captures cumulative atherosclerotic burden, and its clinical value is greatest when it meaningfully reclassifies risk beyond traditional factors. Age, sex, and race-informed percentile approaches can improve interpretability, particularly in younger adults in whom any detectable CAC may be relatively early compared with peers. In a large cohort aged 30–45 years, the distribution of CAC varied substantially by demographic strata, supporting percentile-based contextualization rather than reliance on absolute score alone [9]. A recurring clinical dilemma involves management of patients at borderline or intermediate estimated risk when the net benefit of preventive pharmacotherapy is uncertain. CAC can serve as a treatment-modifying marker in such settings, but its application should remain aligned with the therapeutic question being addressed (eg, statin intensification vs aspirin consideration). Modeling analyses in contemporary cohorts suggest CAC can help identify subgroups more likely to achieve net benefit from aspirin only when bleeding risk is low and absolute atherosclerotic cardiovascular disease (ASCVD) risk is not low, underscoring that CAC should not be used as a standalone trigger for aspirin therapy [10]. Importantly, CAC-guided prevention is most appropriate when combined with structured bleeding-risk assessment and shared decision-making rather than automatic threshold based prescribing [11]. This approach is particularly relevant given that lifetime cardiovascular risk may remain substantial despite low short-term event rates.

Stable Chest Pain and Pre-Test Probability

In stable chest pain evaluation, CAC has been studied as a potential gatekeeper test, particularly to reduce unnecessary downstream imaging in low-to intermediate risk presentations. However, “CAC = 0” should be interpreted as indicating a very low likelihood of obstructive calcified disease rather than guaranteeing absence of atherosclerosis. In a stable chest pain cohort, a zero CAC score demonstrated a high negative predictive value for obstructive stenosis, although a minority of patients still had non-calcified plaque on CCTA [12]. These findings are consistent with a broader meta-analysis showing that CAC = 0 is associated with low event rates among chest pain patients, while not eliminating risk entirely [13]. Large trial-derived analyses further support the prognostic value of CAC in symptomatic populations. In the PROMISE trial, CAC burden stratified risk for major adverse cardiovascular events and provided prognostic information in comparison with functional testing strategies in patients with stable symptoms [14]. Collectively, these data support the use of CAC as a risk modifying input, particularly when the clinical objective is to determine whether CCTA is likely to provide additional actionable information rather than solely to exclude disease. Although a CAC score of zero substantially lowers the likelihood of obstructive calcified coronary disease and is associated with very low short-term event rates, it should not be equated with the absence of atherosclerosis. Non-calcified plaque, including obstructive non-calcified lesions, may still be present, particularly in younger individuals in whom calcification represents a later stage of plaque evolution. Clinical context therefore remains critical. In patients with typical angina, persistent or progressive symptoms, diabetes, heavy smoking exposure, markedly elevated LDL cholesterol, strong family history of premature CAD, or abnormal ECG/troponin findings, a CAC score of zero should not automatically terminate diagnostic evaluation. In such scenarios, further anatomical assessment with CCTA or appropriate functional testing may be warranted. Accordingly, CAC = 0 should be interpreted as a marker of low probability rather than definitive exclusion of clinically relevant CAD, and decision-making should remain guided by pre-test probability and overall risk profile rather than calcium score alone.

CAC-Based Clinical Algorithms

A practical algorithmic approach in stable chest pain is to consider CAC as a front-end triage tool that helps determine whether immediate CCTA is likely to be informative. However, the “power of zero” is most clinically reliable when interpreted alongside explicit clinical exceptions. Post-hoc analyses from the SCOT HEART trial demonstrate that adverse plaque phenotypes and overall plaque burden on CCTA increase with higher CAC strata, while also showing that some patients with CAC = 0 may still harbor substantial non-calcified plaque [15]. Therefore, CAC-only strategies may be best reserved for carefully selected presentations (eg, low-to-intermediate pretest probability without high-risk clinical features), whereas CCTA remains appropriate when symptoms, ECG findings, or overall risk profile justify anatomical clarification despite CAC = 0 [12,15]. Evidence also supports the use of CAC to inform follow up timing and rescanning intervals in prevention settings. In the Multi-Ethnic Study of Atherosclerosis (MESA), progression from CAC = 0 to detectable CAC was modeled, and the estimated “warranty period” varied meaningfully according to demographics and baseline risk profile, with diabetes associated with shorter intervals [16]. These findings support individualized rescanning strategies rather than uniform time-based repetition. Finally, recent DISCHARGE-related analyses have emphasized that CAC = 0 generally indicates very low short-term event rates in stable chest pain, while also highlighting the need for more nuanced definitions of low risk that incorporate symptom context and the intended purpose of downstream testing [17]. The clinical objective is not simply to avoid testing, but to avoid non-informative testing, and optimal implementation strategies remain an area of ongoing investigation. The clinical integration of CAC scoring across preventive and diagnostic pathways is summarized in Figure 1.

Figure 1 Clinical integration of coronary artery calcium (CAC) scoring in cardiovascular risk assessment and diagnostic decision-making. CAC is measured using non-contrast cardiac computed tomography with Agatston score quantification in asymptomatic adults with borderline/intermediate atherosclerotic cardiovascular disease (ASCVD) risk and in patients with stable chest pain and low–intermediate pre-test probability. Increasing CAC categories (0, 1–99, 100–399, ≥400) reflect progressively higher cumulative atherosclerotic plaque burden and are associated with stepwise escalation in cardiovascular risk, preventive therapy intensity, and diagnostic considerations. A CAC score of zero identifies individuals with very low short-term event risk but does not exclude non-calcified atherosclerosis. Higher CAC burdens favor statin initiation or intensification and may influence the selection and interpretation of coronary computed tomographic angiography (CCTA), particularly at very high scores where blooming artifacts may reduce diagnostic specificity. CAC findings should always be interpreted within the overall clinical context and are not intended as a standalone diagnostic tool.

Prediction of Cardiovascular Events

CAC scoring demonstrates a robust, graded association with future cardiovascular events across both asymptomatic and symptomatic populations. Higher CAC burden is associated with progressively increased risk of myocardial infarction, cardiovascular mortality, and all cause mortality, supporting CAC as a marker of cumulative atherosclerotic exposure rather than transient plaque activity [1,14]. CAC should therefore be interpreted as a continuous risk marker rather than solely according to categorical thresholds. Very high CAC appears to represent a distinct extreme risk phenotype. In the MESA, individuals with CAC ≥1000 had markedly higher risks for cardiovascular and non cardiovascular outcomes, with an annualized 3-point major adverse cardiovascular event (MACE) rate of 3.4 per 100 person-years, comparable to rates reported in treated secondary prevention settings [18]. These findings have important implications for preventive intensity and clinical surveillance strategies and suggest that the upper tail of the CAC distribution may warrant more aggressive preventive approaches than implied by conventional ≥400 groupings. In symptomatic patients, CAC retains prognostic relevance. Meta-analytic evidence indicates that CAC = 0 is associated with low short-term event rates among chest pain populations, but risk is not eliminated, partly because non-calcified plaque can still be present [12,13]. Accordingly, CAC should be interpreted within the broader clinical context rather than as a binary rule-out test. The clinical interpretation of commonly used CAC categories and their associated short- and long-term risk profiles is summarized in Table 1.

Table 1: Clinical interpretation of CAC categories and associated cardiovascular risk.

Abbreviations: CAC: coronary artery calcium, ASCVD: atherosclerotic cardiovascular disease, MACE: major adverse cardiovascular events.

Incremental Prognostic Value Beyond Traditional Risk Factors

Traditional risk equations estimate probability using demographic and clinical variables but do not directly quantify coronary atherosclerosis. CAC improves risk estimation by providing an anatomical measure of disease burden that integrates the cumulative effects of lifetime risk exposures. In comparative risk-prediction analyses, adding CAC to traditional risk-factor models significantly improves discrimination and clinically relevant risk reclassification. In a head-to-head evaluation in the MESA and Rotterdam Study cohorts, CAC significantly improved discrimination and categorical net reclassification at treatment-relevant thresholds, whereas a polygenic risk score did not provide comparable categorical reclassification value [19]. These findings support CAC as a clinically meaningful risk integrator that captures the net effect of lifetime exposures on subclinical disease.

Why CAC “Amount” is not the Whole Story: Volume vs Density

The Agatston score combines lesion area with a density weighting factor, which may obscure clinically important heterogeneity. In the MESA cohort, CAC volume was directly associated with coronary heart disease and cardiovascular disease events, whereas higher CAC density (at a given volume) was inversely associated with risk [20]. This observation suggests that two individuals with similar Agatston scores may not share identical risk profiles if the composition of calcium differs, supporting reporting frameworks that consider volume and density metrics when feasible.

Sex, Age, and Long-Term Mortality

Interpretation of CAC requires demographic context. Early-onset CAC in younger adults is clinically meaningful, with meta-analytic data demonstrating higher event and mortality risk among younger individuals with detectable CAC compared with those with CAC = 0 [21]. Long-term mortality data also highlight sex-related differences. In a 15-year follow-up cohort, mortality increased stepwise across CAC categories in both sexes, and women with CAC >10 demonstrated higher mortality risk compared with men, supporting CAC as a tool to improve risk detection in women beyond traditional factors alone [20]. Finally, longitudinal evidence indicates that the “warranty period” associated with CAC = 0 is not uniform and varies according to baseline risk profile, reinforcing the need for individualized rather than fixed rescanning intervals [16]. These observations further emphasize the importance of contextualizing CAC findings within demographic and clinical risk characteristics.

CAC-Guided Statin Initiation and Intensification

In contemporary preventive cardiology, CAC scoring is most clinically informative when it alters the expected net benefit of lipid-lowering therapy. Both the 2018 American College of Cardiology / American Heart Association (ACC/AHA) cholesterol guideline and the 2019 ACC/AHA primary prevention guideline endorse CAC assessment as a decision aid for adults in whom statin benefit remains uncertain after a clinician–patient risk discussion [2,22]. Similarly, European prevention guidance recognizes the utility of imaging markers of subclinical atherosclerosis, including CAC, to refine risk estimation and inform the intensity of preventive therapy when baseline risk classification is ambiguous [23].

A pragmatic interpretation is that CAC redefines risk along a continuum rather than simply confirming eligibility. Patients with CAC = 0 consistently demonstrate very low short-term event rates, frequently below 1% over 5 years in intermediate-risk populations, supporting the concept that absence of coronary calcification identifies a subgroup with favorable short-term prognosis. However, CAC = 0 should not be considered a universal reason to defer pharmacotherapy. Patients with diabetes, heavy smoking exposure, or a strong family history may still warrant treatment despite the absence of calcification, depending on the overall clinical context [2,22]. Although CAC-guided strategies improve risk stratification, randomized outcome data supporting treatment decisions based solely on CAC findings remain limited.

Very high CAC burden (≥1000) appears to define a distinct extreme-risk phenotype, with event rates approaching those observed in secondary prevention cohorts. This observation suggests that the upper tail of the CAC distribution may warrant preventive strategies comparable in intensity to those used after established atherosclerotic cardiovascular disease, although randomized trial confirmation is lacking. This concept is clinically relevant because conventional CAC categories (eg, ≥400) may underestimate the risk gradient at the upper tail of the distribution [18].

CAC also clarifies the interpretation of risk-enhancing factors. In the MESA, CAC improved discrimination and net reclassification beyond the presence of risk-enhancing factors, and intermediate-risk individuals with CAC = 0 generally had low absolute event rates even when multiple enhancers were present [24]. These findings suggest that CAC may help reduce overtreatment driven by heterogeneous risk-enhancing profiles while still identifying individuals in whom risk enhancers and CAC jointly signal high absolute risk [24,25].

Although a CAC score of zero is consistently associated with a favorable short-term prognosis and may support deferral of statin therapy in many borderline or intermediate-risk individuals, this finding should not be interpreted as universal treatment exemption. In patients with high clinical risk profiles, particularly those with diabetes mellitus, heavy smoking exposure, markedly elevated LDL cholesterol levels, strong family history of premature coronary artery disease, or multiple risk- enhancing conditions, the so-called “power of zero” appears attenuated, and substantial lifetime cardiovascular risk may persist despite absence of detectable calcification. In such individuals, risk communication should emphasize low near-term event probability rather than absence of disease, and statin therapy may remain appropriate as part of a comprehensive preventive strategy.

Aspirin Allocation and Net Benefit

Primary prevention aspirin decisions require balancing modest cardiovascular benefit against bleeding risk. Contemporary evidence and guidelines emphasize individualized decision-making rather than routine use, particularly as bleeding risk increases with age [22,26]. In this context, CAC can serve as a risk marker that helps identify subgroups in whom ASCVD risk may be sufficiently high for aspirin benefit to outweigh harm when bleeding risk is low.

MESA-based analyses support the principle that higher CAC burden may indicate a more favorable net benefit profile for aspirin therapy, whereas CAC = 0 tends to identify individuals in whom net harm is more likely [10,11]. Nevertheless, CAC should not override clinical bleeding risk assessment; rather, it provides an additional dimension for estimating the absolute event risk required for any antithrombotic strategy to be justified. Optimal CAC thresholds for aspirin allocation remain uncertain and should be interpreted within individualized clinical decision-making frameworks [10,26]. A practical framework integrating CAC findings with preventive pharmacotherapy and diagnostic decision-making across common clinical scenarios is outlined in Table 2.

Table 2: CAC-Guided Diagnostic and Preventive Decisions Including Statin and Aspirin.

Abbreviations: CAC: coronary artery calcium, ASA: acetylsalicylic acid (aspirin), PTP: pre-test probability, CCTA: coronary computed tomographic angiography, ASCVD:

atherosclerotic cardiovascular disease.

Beyond Lipids and Aspirin: Hypertension, Diabetes, and Global Prevention Intensity

CAC may also influence the overall intensity of preventive strategies. While CAC is not itself a treatment target, it can function as a shared decision-making tool that supports earlier or more intensive implementation of proven interventions, such as stricter blood pressure control, optimization of metabolic risk factors, and comprehensive lifestyle interventions, in patients with substantial subclinical disease [22,23]. In practice, the most appropriate use case is not the addition of novel therapies solely because CAC is elevated, but rather ensuring that established, guideline-directed interventions are consistently implemented and maintained when atherosclerotic burden is demonstrably present [2,22].

Patient Behavior, Adherence, and Downstream Management

CAC scoring is often discussed as a “motivational” test, but potential behavioral effects should be interpreted cautiously. Observational data suggest that CAC testing is associated with changes in management, including increased initiation or intensification of lipid-lowering therapy and other preventive interventions in patients with higher CAC categories [27]. However, these associations do not establish causality, as downstream decisions may also be influenced by clinician preference, baseline risk profile, and healthcare access.

When CAC is used, structured communication is critical. Presenting CAC results as an absolute risk modifier, linking findings to specific preventive actions, and documenting a clear follow-up plan may reduce the likelihood that CAC becomes an isolated data point without therapeutic translation [22,27]. For individuals with CAC = 0, follow- up discussions should emphasize that low short-term risk does not equate to lifetime immunity, consistent with evidence demonstrating that the duration of the so-called warranty period varies across baseline risk profiles [16]. Structured reporting strategies and clinician education may further improve translation of CAC findings into clinical practice.

Blooming Artifacts and Overestimation of Stenosis

Extensive coronary calcification presents well- recognized technical challenges in CCTA. High-density calcium produces blooming artifacts due to partial volume effects and limited spatial resolution, which may lead to overestimation of luminal stenosis severity [3]. As CAC burden increases, the specificity of CCTA for detecting obstructive disease declines, particularly in segments with confluent calcification. These diagnostic limitations occur along a spectrum rather than as a binary phenomenon. Studies evaluating the relationship between CAC burden and CCTA accuracy demonstrate that specificity and positive predictive value decrease as Agatston scores rise, especially beyond conventional thresholds of 400 [28]. Contemporary multidetector CT systems and advanced reconstruction techniques can mitigate, but do not eliminate, calcium- related artifacts.

Diagnostic Accuracy of CCTA at High CAC Levels

The interaction between CAC burden and CCTA diagnostic performance has been evaluated in multiple cohorts. In patients with CAC ≥400, CCTA sensitivity for detecting obstructive CAD generally remains high, whereas specificity declines because of blooming-related luminal overestimation [28,29]. Even in individuals with CAC ≥1000, CCTA often maintains a high negative predictive value, although stenosis severity may be overestimated and nondiagnostic segments become more frequent [29]. These findings suggest that while CCTA remains technically feasible in many patients with high CAC, diagnostic confidence decreases at the upper end of the calcium spectrum.

Importantly, a high CAC score does not necessarily indicate hemodynamically significant stenosis. Extensive calcification reflects cumulative plaque burden but does not directly quantify luminal obstruction. Therefore, reliance on CAC alone to infer obstructive coronary disease may be misleading, and optimal CAC thresholds for determining CCTA feasibility remain uncertain.

Alternative Strategies in the Presence of Extensive Calcification

When CAC burden is extremely high or when CCTA yields nondiagnostic segments because of artifact, alternative diagnostic pathways should be considered. Functional testing modalities, including stress echocardiography, myocardial perfusion imaging, or stress cardiac magnetic resonance, may provide physiologic assessment without the anatomical limitations imposed by calcification [14]. In selected high-risk symptomatic patients with extensive calcification and persistent clinical suspicion, invasive coronary angiography remains the reference standard for anatomical evaluation.

Hybrid strategies integrating anatomical and functional information may also be useful in selected cases. Ultimately, the choice of diagnostic pathway should be guided primarily by clinical presentation rather than CAC score alone, emphasizing that CAC should be interpreted within the broader clinical context.

Guideline Recommendations

Contemporary cardiovascular guidelines recognize CAC scoring as a valuable tool for refining risk assessment and guiding preventive therapy in selected populations. The 2018 ACC/AHA cholesterol guideline and the 2019 ACC/AHA primary prevention guideline recommend CAC measurement in adults with borderline or intermediate estimated risk when treatment decisions remain uncertain after clinician–patient discussion [2,22]. Similarly, European prevention guidelines acknowledge the role of imaging markers of subclinical atherosclerosis, including CAC, in improving risk stratification beyond traditional clinical variables [23].

In the evaluation of stable chest pain, guideline recommendations are more heterogeneous. While CAC may serve as a gatekeeper test in low-risk symptomatic individuals, most contemporaryguidanceemphasizes CCTA as the preferred initial anatomical test when obstructive disease is suspected, with CAC serving a complementary rather than primary diagnostic role [22,23]. A comparative overview of how ACC/AHA and ESC guidelines incorporate CAC into cardiovascular risk stratification and preventive decision-making is presented in Table 3.

Table 3: Comparison of CAC Utilization in ACC/AHA and ESC Prevention Guidelines.

Abbreviations: CAC: coronary artery calcium, ASCVD: atherosclerotic cardiovascular disease, ACC/AHA: American College of Cardiology/American Heart Association, ESC: European Society of Cardiology, CCTA: coronary computed tomographic angiography.

Gap Between Guidelines and Daily Practice

Despite strong evidence and guideline endorsement, the real-world implementation of CAC scoring remains inconsistent. Barriers include limited access to imaging, variability in reimbursement policies, lack of clinician familiarity with interpretation, and uncertainty regarding how CAC results should modify treatment intensity. Geographic and socioeconomic disparities may further influence access to CAC testing across healthcare systems.

Observational data suggest that CAC testing may be underutilized in populations where it could provide the greatest clinical value, particularly among intermediate- risk individuals in whom preventive decisions are uncertain [27]. Conversely, CAC may occasionally be applied in low-risk populations where results are unlikely to alter management, thereby reducing cost-effectiveness.

Another practical challenge involves interpretation of extreme CAC values. Guidelines provide general thresholds but limited detailed recommendations for management of very high scores, leaving clinicians to extrapolate preventive intensity from observational risk estimates [18]. This uncertainty contributes to heterogeneity in clinical practice, and future guideline updates may provide more granular recommendations for patients with extreme CAC burden.

Cost-effectiveness analyses generally support CAC-guided prevention strategies in appropriately selected populations, particularly when testing avoids unnecessary pharmacotherapy or downstream diagnostic procedures [23]. However, healthcare system structure and reimbursement policies strongly influence implementation. Improving translation into practice will likely require clinician education, standardized reporting frameworks, and health system–level support.

Additional limitations relate to potential overuse and cost implications. CAC testing may lead to downstream investigations that do not ultimately alter management, particularly when applied in very low-risk populations. Furthermore, variability in access, reimbursement policies, and clinician familiarity may influence real-world implementation and external validity across healthcare systems. Finally, most evidence supporting CAC-guided decision-making derives from observational cohorts rather than randomized trials, which should be considered when interpreting causal implications.

Limitations of CAC Scoring

Despite its strong prognostic value and reproducibility, CAC scoring has several inherent limitations. First, CAC reflects only calcified plaque and does not directly capture non-calcified or lipid-rich atherosclerotic components, which may still confer clinically significant risk, particularly in younger individuals and those with acute coronary syndromes [8,12]. Consequently, a CAC score of zero should not be interpreted as complete absence of atherosclerosis.

Second, CAC progression remains difficult to interpret clinically. Although increases in CAC over time correlate with cumulative plaque burden, the relationship between CAC progression and modification of clinical outcomes under contemporary medical therapy remains uncertain [1]. Statin therapy, for example, may increase calcium density while stabilizing plaque, thereby complicating interpretation of serial measurements (30). Consequently, progression of CAC does not uniformly translate into higher clinical risk, and absolute changes in Agatston score should not be used as treatment response markers. The absence of randomized evidence demonstrating improved outcomes through serial CAC monitoring further limits its role in routine follow-up, supporting current recommendations against repeated scanning solely to assess therapeutic efficacy.

Radiation exposure, although relatively low with modern scanners, remains a consideration, particularly when serial imaging is performed. Furthermore, CAC scoring does not provide information regarding stenosis severity or plaque morphology, limiting its utility in symptomatic populations without complementary imaging. The principal strengths, limitations, and key clinical pitfalls of CAC scoring in contemporary practice are summarized in Table 4.

Table 4: Strengths and limitations of CAC scoring in contemporary practice.

Abbreviations: CAC: coronary artery calcium, CCTA: coronary computed tomographic angiography, NPV: negative predictive value, ASCVD: atherosclerotic cardiovascular disease.

Controversies in Clinical Application

Several controversies persist regarding the optimal clinical implementation of CAC scoring. One debated issue is the role of serial CAC measurement for monitoring therapeutic  response.  While  observational  studies demonstrate associations between CAC progression and event risk, there is insufficient randomized evidence to support routine serial scanning as a treatment-monitoring strategy [1,16]. Another area of uncertainty involves interpretation of very high CAC scores. Although extreme CAC (≥1000) identifies individuals with markedly elevated risk, guidelines provide limited specific management recommendations beyond aggressive risk factor control [18]. This leaves clinicians to extrapolate treatment intensity from observational risk gradients rather than trial-based thresholds.

The role of CAC in symptomatic patients also remains debated. While CAC may function as a gatekeeper in low- risk chest pain populations, reliance on CAC alone may miss non-calcified obstructive disease, reinforcing the importance of careful clinical selection [12,13].

Emerging Technologies and Artificial Intelligence

Advances in imaging technology and artificial intelligence (AI) are expanding the potential applications of CAC analysis. Automated CAC quantification from non-gated chest CT scans has demonstrated promising accuracy, potentially enabling opportunistic screening without additional radiation exposure or dedicated imaging sessions [3].

AI-based plaque characterization and risk prediction models may further enhance integration of CAC with other imaging biomarkers, including perivascular fat attenuation and quantitative plaque features derived from CCTA [15]. Such multiparametric approaches may improve individualized risk prediction beyond calcium burden alone.

CAC scoring has evolved into an important tool for cardiovascular risk assessment, providing a direct and reproducible measure of cumulative atherosclerotic burden. Extensive evidence indicates that CAC offers robust prognostic information across both asymptomatic and symptomatic populations, with a graded association between calcium burden and cardiovascular events that extends beyond traditional risk factors alone [1,14]. Importantly, CAC facilitates more precise risk stratification, particularly among individuals with borderline or intermediate estimated risk, in whom treatment decisions often remain uncertain.

In contemporary cardiology practice, the clinical utility of CAC extends beyond risk prediction to therapeutic decision-making. CAC-guided strategies may inform initiation and intensification of preventive therapies, improve allocation of statins and aspirin in selected populations, and support individualized patient counseling. At the same time, clinicians should recognize the limitations of CAC, including its inability to detect non-calcified plaque and its limited role as a standalone diagnostic tool in symptomatic patients. Accordingly, CAC should be interpreted within the broader clinical context rather than as an isolated measurement.

Integration of CAC with CCTA further enhances its clinical relevance. While extensive calcification may reduce CCTA specificity because of blooming artifacts, combined anatomical and functional assessment strategies allow more tailored diagnostic pathways in patients with high calcium burden. As imaging technology advances, automated quantification and multiparametric plaque assessment may further expand the role of CAC within comprehensive cardiovascular imaging frameworks.

All of the authors contributed planning, conduct, and reporting of the work. All authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

The authors confirm that no artificial intelligence or AI-assisted tools were used for interpreting the referenced article or for generating scientific content. Limited assistance was obtained solely for language editing and grammatical refinement, without any involvement in data interpretation, analysis, or conceptual input.

1. Greenland P, Blaha MJ, Budoff MJ, Erbel R, Watson KE. Coronary calcium score and cardiovascular risk. J Am Coll Cardiol. 2018; 72: 434-447.
2. Grundy SM, Stone NJ, Bailey AL. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 139: e1082-e1143.
3. Dzaye O, Razavi AC, Jelwan YA, Peng AW, Grant JK, Blaha MJ. Coronary artery calcium scoring on dedicated cardiac CT and noncardiac CT scans. Radiol Cardiothorac Imaging. 2025; 7: e240548.
4. Neves PO, Andrade J, Monção H. Coronary artery calcium score: current status. Radiol Bras. 2017; 50: 182-189.
5. Cheong BYC, Wilson JM, Spann SJ, Pettigrew RI, Preventza OA, Muthupillai R. Coronary artery calcium scoring: an evidence-based guide for primary care physicians. J Intern Med. 2021; 289: 309-324.
6. Czaja-Zió?kowska MZ, Wasilewski J, G?sior M, G?owacki J. An update on the coronary calcium score: a review for clinicians. Postepy Kardiol Interwencyjnej. 2022; 18: 201-205.
7. Rijlaarsdam-Hermsen D, Kuijpers D, van Domburg RT, Deckers JW. Prognostic value of the coronary artery calcium score in suspected coronary artery disease: a study of 644 symptomatic patients. Neth Heart J. 2020; 28: 44-50.
8. Jonas RA, Nurmohamed NS, Crabtree TR, Aquino M, Jennings RS, Choi AD, et al. CTA-derived plaque characteristics and risk of acute coronary syndrome in patients with coronary artery calcium score of zero: insights from the ICONIC trial. AJR Am J Roentgenol. 2025; 225: E2431476.
9. Javaid A, Dardari ZA, Mitchell JD, Whealton SP, Dzaye O, Lima JAC, et al. Distribution of coronary artery calcium by age, sex, and race among patients 30-45 years old. J Am Coll Cardiol. 2022; 79: 1873-1886.
10. Cainzos-Achirica M, Miedema MD, McEvoy JW, Rifai MA, Greenland P, Dardari Z, et al. Coronary artery calcium for personalized allocation of aspirin in primary prevention of cardiovascular disease in 2019: the MESA study (Multi-Ethnic Study of Atherosclerosis). Circulation. 2020; 141: 1541-1553.
11. Ajufo E, Ayers CR, Vigen R, Joshi PH, Rohatgi A, de Lemos JA, et al. Value of coronary artery calcium scanning in association with the net benefit of aspirin in primary prevention of atherosclerotic cardiovascular disease. JAMA Cardiol. 2021; 6: 179-187.
12. Wang X, Le EPV, Rajani NK, Hudson Peacock NJ, Pavey H, Tarkin JM, et al. A zero coronary artery calcium score in patients with stable chest pain is associated with a good prognosis, despite risk of non-calcified plaques. Open Heart. 2019; 6: e000945.
13. Agha AM, Pacor J, Grandhi GR, Mszar R, Khan SU, Parikh R, et al. The prognostic value of CAC zero among individuals presenting with chest pain: a meta-analysis. JACC Cardiovasc Imaging. 2022; 15: 1745-1757.
14. Budoff MJ, Mayrhofer T, Ferencik M, Bittner D, Lee KL, Lu MT, et al. Prognostic value of coronary artery calcium in the PROMISE study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Circulation. 2017; 136: 1993-2005.
15. Osborne-Grinter M, Kwiecinski J, Doris M, Cadet S, Adamson PD, Moss AJ, et al. Association of coronary artery calcium score with qualitatively and quantitatively assessed adverse plaque on coronary CT angiography in the SCOT-HEART trial. Eur Heart J Cardiovasc Imaging. 2022; 23: 1210-1221.
16. Dzaye O, Dardari ZA, Cainzos-Achirica M, Blankstein R, Agatston AS, Duebgen M, et al. Warranty period of a calcium score of zero: comprehensive analysis from MESA. JACC Cardiovasc Imaging. 2021; 14: 990-1002.
17. Hanneman K, Gulsin GS. Significance of a coronary artery calciumscore of 0 in stable chest pain. Radiology. 2024; 310: e240073.
18. Peng AW, Dardari ZA, Blumenthal RS. Very high coronary artery calcium (≥1000) and association with cardiovascular disease events, non-cardiovascular disease outcomes, and mortality: results from MESA. Circulation. 2021; 143: 1571-1583.
19. Khan SS, Post WS, Guo X, Tan J, Zhu F, Bos D, et al. Coronary artery calcium score and polygenic risk score for the prediction of coronary heart disease events. JAMA. 2023; 329: 1768-1777.
20. Kelkar AA, Schultz WM, Khosa F, Gransar H, Blaha MJ, Knapper JT, et al. Long-term prognosis after coronary artery calcium scoring among low-intermediate risk women and men. Circ Cardiovasc Imaging. 2016; 9: e003742.
21. Haq A, Veerati T, Walser-Kuntz E, Aldujeli A, Tang M, Miedema M. Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis. Eur J Prev Cardiol. 2024; 31: 1061-1069.
22. Arnett DK, Blumenthal RS, Albert MA. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140: e563-e595.
23. Visseren FLJ, Mach F, Smulders YM, Carballo D, Back M, Benetos A, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021; 42: 3227-3337.
24. Patel J, Al Rifai M, Blaha MJ, Virani SS, Shea S, Yeboah J, et al.Assessment of Coronary Artery Calcium Scoring to Guide StatinTherapy Allocation According to Risk-Enhancing Factors: The Multi- Ethnic Study of Atherosclerosis. JAMA Cardiol. 2021; 6: 1161-1170.
25. Dzaye O, Dudum R, Reiter-Brennan C, Kianoush S, Blaha MJ. Coronary artery calcium scoring for individualized cardiovascular risk estimation in important patient subpopulations after the 2019 AHA/ ACC primary prevention guidelines. Prog Cardiovasc Dis. 2019; 62: 423-430.
26. Davidson KW, Mangione CM, Barry MJ; US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022; 327: 1577-1584.
27. Wu WY, Biery DW, Berman AN, Hseih G, Divakaran S, Gupta S, et al. Impact of coronary artery calcium testing on patient management. J Cardiovasc Comput Tomogr. 2022; 16: 303-308.
28. Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the ACCURACY trial. J Am Coll Cardiol. 2008; 52: 1724-1732.
29. Kwan AC, Leipsic J, Budoff MJ. The accuracy of coronary CT angiography in patients with coronary calcium score above 1000 Agatston units: comparison with quantitative coronary angiography. J Cardiovasc Comput Tomogr. 2021; 15: e1-e9.
30. Criqui MH, Knox JB, Denenberg JO. Coronary artery calcium volume and density: potential interactions and overall predictive value: the Multi-Ethnic Study of Atherosclerosis. JACC Cardiovasc Imaging. 2017; 10: 845-854.