• Atherosclerotic Disease Risk Factors Can Guide First Coronary Artery Calcium Scan Timing in Young Adults – CAC Consortium Analysis

    Risk factor profiles for atherosclerotic cardiovascular disease (ASCVD), including diabetes, smoking, hypertension, dyslipidemia and family history, can be used to determine the recommended age for a first coronary artery calcium (CAC) scan in young adults to determine those susceptible for premature disease, a new CAC Consortium analysis of has found.

    There are currently no recommendations guiding when best to perform a CAC scan in young adults to identify those susceptible for developing premature atherosclerosis, the researchers – led by John Hopkins University School of Medicine’s Omar Dzaye, MD, MPH, PhD – said.

    In the U.S. study’s 22,346 participants (aged 30 – 50 years), the optimal age for a first CAC scan was around 42 years in men or 58 years in women without risk factors for premature atherosclerosis, but those ages reduced to 37 years in men and 50 years in women who were diabetic.

    The findings were published Monday online ahead of the Oct. 19 issue of the Journal of the American College of Cardiology.

    CAC – as measured by non-contrast computed tomography (CT) scan – is a non-invasive measure of subclinical coronary atherosclerosis that is “strongly associated with incident coronary heart disease (CHD)” and ASCVD, the researchers noted.

    It is recommended as a prognostic indicator for risk stratification in adults up to 40 years of age at borderline or intermediate risk when there is uncertainty over whether to give primary prevention pharmacotherapy, the researchers said.

    Despite its potential usefulness in clinical decision-making for young adults (age 30 – 50 years) with ASCVD risk factors, optimal timing and determinants of CAC becoming more severe are unknown.

    Although ASCVD is commonly predicted in older adults based on CAC scores of >0 or >100 – suggesting potential for progression toward very high CAC scores of 1,000 or more – “such approaches may have limited value in younger adults because of the strong reliance of ASCVD risk equations on age, and the lower expected CAC burden in young adults,” the researchers said.

    “Predicting the initial conversion to CAC >0 can help to determine the recommended age for initiating CAC testing in younger adults and identify at-risk individuals several years to decades before the onset of clinical CHD,” they added, and could allow for timely initiation of preventive measures in those most susceptible.

    The current study was, therefore, established to determine the prevalence, characteristics and predicted growth rate of premature CAC, as well as to model the probability and initial age of conversion to CAC >0 according to the presence of ASCVD risk factors.

    Participants aged between 30 and 50 years were recruited in the CAC Consortium from 1991 to 2010, a multi-center cohort study in four high-volume U.S. centers: Cedars-Sinai Medical Center, Los Angeles; PrevaHealth Wellness Diagnostic Center, Columbus, Ohio; Harbor UCLA Medical Center, Torrance, California; and Minneapolis Heart Institute, Minneapolis.

    Average age was 43.5 ± 4.5 years, most were male (75%), predominantly white (87.7%) and the majority had a 10-year ASCVD risk below 5% (92.7%), with 4.7% in the 5-7% 10-year risk category and 2.6% above 7.5% risk.

    Subjects underwent non-contrast CT scan, and sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors.

    Of the 22,346 participants, 7,686 (34.4%) had CAC >0, among which the median CAC score was 20 Agatston units (AU), and of whom 6,080 (79.1%) had prevalent CAC <100.

    Dyslipidemia (49.6%) and a family history of CHD (49.3%) were the most common ASCVD risk factors, while 20.1% had hypertension, 11% were active smokers, and 4% had diabetes. Still, the majority of participants (92.7%) had low 10-year risk.

    Participants without traditional risk factors were projected to convert to CAC >0 at 42.3 years (95% confidence interval [CI]: 41.0-43.9 years) if male, and 57.6 years (95% CI: 56.0-59.5 years) if female, whereas those with one or more risk factors would convert to CAC >0 at least 3.3 years earlier on average, assuming a 25% testing yield.

    Of all the ASCVD risk factors, diabetes was found to have the most robust association with earlier conversion to CAC >0, a greater magnitude effect in women (β = 0.71) than men (β = 0.63), and the strongest influence on the CAC >0 offset period, with men and women developing incident CAC a respective 5.5 years and 7.3 years earlier on average than non-diabetics. 

    Dyslipidemia was also strongly associated with increased risk for premature CAC in both women (β = 0.54) and in men (β = 0.34). Those with dyslipidemia, hypertension, who were current cigarette smokers or who had a family history of CHD were each individually associated with developing CAC 3.3-4.3 years earlier than non-risk-factor participants.

    “To our knowledge, this is the first study to derive clinical risk equations for the initial conversion from CAC = 0 to CAC ≥1, which can be used to guide the timing of initiating CAC testing in young adults,” the researchers said.

    “Current guidelines recommend consideration of CAC scoring in selected adults with a 10-year ASCVD risk between 5% - 19.9%; however, our findings demonstrate a potential utility for CAC scanning among a subgroup of young adults at-risk for CHD who almost all had a 10-year risk.”

    They added that additional risk calculators that are derived from more diverse populations and genetic data are important in guiding primary preventive therapy.

    In an accompanying editorial, Tasneem Z. Naqvi, MD, MMM, Mayo Clinic, and Tamar S. Polonsky, MD, MSCI, University of Chicago, stressed the benefits of preventive therapy strategies in older adults at high risk for ASCVD, stressing this has “contributed to a substantial decline in the incidence and mortality from [myocardial infarction]”.

    The current study provides “additional concrete information” over appropriate prevention strategies in younger adults, they said.


    Dzaye O, Razavi AC, Dardari ZA, et al. Modeling the Recommended Age for Initiating Coronary Artery Calcium Testing Among At-Risk Young Adults. J Am Coll Cardiol 2021;78:1573-1583.

    Naqvi TZ, Polonsky T. Finding the Right Age for CAC Testing How Low Should You Go? J Am Coll Cardiol 2021;78:1584-1586.

    Image Credit: Kateryna_Kon – stock.adobe.com

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