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  • Observational Study: High CAC Associated with Increased Risk of All-Cause Death, Cardiovascular Outcomes

    Outside traditional risk prediction methods, patients with coronary artery calcium (CAC) ≥100 are at an increased risk of all-cause death and adverse cardiovascular outcomes, a new study shows.

    This information was reported by Allison W. Peng, MD, of Stanford University, and colleagues, in a manuscript published Monday online and in the Sept. 19 issue of the Journal of the American College of Cardiology.

    All racial and ethnic groups demonstrate increased risk of cardiovascular events from CAC levels. Nonelectrocardiography (ECG)-gated computed tomography (CT) can be used to quantify CAC when it is used to determine other diagnoses, making it an optimal opportunity to screen for subclinical atherosclerosis.

    The investigators of this study examined how routine non-ECG-gated CTs predicted incidental CAC. A deep-learning (DL) algorithm was used to provide cardiovascular risk stratification beyond traditional methods of predicting cardiovascular risk. Electronic health records were gathered from the Stanford Research Repository Clinical Data Warehouse. The primary outcome of this study was all-cause death.

    A DL algorithm (DL-CAC) was used to quantify CAC on non-ECG-gated chest CTs performed in routine care settings between 2014 and 2019. The association between DL-CAC (0, 1-99, or ≥100) and all-cause death was measured, as well as the secondary outcomes of death/myocardial infarction (MI) and death/MI/stroke/revascularization (measured using Cox regression). The investigators adjusted for age, sex, race, ethnicity, comorbidities, systolic blood pressure, lipid levels, smoking status and use of antihypertensives. Pooled cohort equations were used to calculate 10-year atherosclerotic cardiovascular disease (ASCVD).

    A total of 5,678 adult patients (51% female, 54% white, 18% Asian, 13% Hispanic/Latinx) without ASCVD were included in the study, and mean follow-up was 4.8 ± 2.7 years. The average 10-year ASCVD risk in patients with DL-CAC ≥100 was 24%, and 26% of those patients were on statins. Risk of death also increased in this group after adjustments (hazard ratio [HR]=1.51; 95% confidence interval [CI]=1.45-1.79) compared with the DL-CAC=0 group, as well as death/MI/stroke (HR=1.57; 95% CI=1.33-1.84) and death/MI/stroke/revascularization (HR=1.69; 95% CI=1.45-1.98).

    Some limitations of this study included those inherent with a single-center study, but the investigators examined CT scans from multiple locations within the institution to reduce this bias. The results may not be generalizable to sicker cohorts or patients who had prior CT scans, and absolute event rates may not be directly comparable to 10-year ASCVD risk because the primary outcome was not isolated to cardiovascular-related deaths.

    Overall, patients with DL-CAC had worse outcomes, especially patients with DL-CAC ≥100. Patients with DL-CAC ≥100 had a higher risk of death and adverse cardiovascular outcomes. The authors added that the study shows the potential for non-ECG-gated CT to serve as a screening tool that might prompt earlier intervention in patients who stand to benefit.

    In an accompanying editorial, Roger S. Blumenthal, MD, Jelani Grant, MD, and Seamus P. Whelton, MD, MPH, of the Johns Hopkins School of Medicine, Baltimore, discussed the history of ECG-gated CAC scoring and how it relates to management of ASCVD risk.

    The editorialists wrote, “There are many shared risk factors for CVD and cancer, and persons who undergo chest CT as part of a diagnostic, prognostic, or surveillance imaging are especially likely to benefit from reporting of incidental CAC,” describing the potential contribution of this study to all patients who undergo noncardiac chest CT scans.

    The commenters concluded by describing the benefits of the study for the growing ASCVD population.

    “The pragmatic use of this AI algorithm and increased uptake for reporting of incidental CAC has the potential to transform the appropriate allocation of primary prevention medications, motivate asymptomatic adults to make sustained lifestyle improvements, reduce the burden of ASCVD, and potentially reverse the recent trend of increased ASCVD in the United States,” wrote the editorialists.


    Peng AW, Dudum R, Jain SS, et al. Association of Coronary Artery Calcium Detected by Routine Ungated CT Imaging With Cardiovascular Outcomes. J Am Coll Cardiol. 2023;82:1192-1202.

    Blumenthal RS, Grant J, Whelton SP. Incidental Coronary Artery Calcium: Nothing Is More Expensive Than a Missed Opportunity. J Am Coll Cardiol. 2023;82:1203-1205.

    Image Credit: Pepermpron –

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