Atherosclerosis begins before birth and progresses throughout life.^[1] Calcific atherosclerosis has been demonstrated in human cultures for at least 5,300 years^[2] and was commonplace in many ancient cultures.^[3] The modern day Tsimane tribe of the Bolivian Amazon demonstrates the potential preventive power of a lifetime of minimal atherosclerotic cardiovascular disease (ASCVD) risk factors. They live a subsistence lifestyle of hunting, gathering, fishing, and farming and have an estimated lifetime low-density lipoprotein cholesterol (LDL-C) of ≈71 mg/dL. Coronary artery calcium (CAC) scanning of 705 Tsimane adults found their CAC to be approximately one-fifth the level observed in a U.S. industrialized population.^[4]

CAC is a well-established marker of coronary atherosclerosis burden and strongly predicts ASCVD events in young^[5] and in middle-aged and older^[6]adults. It is useful for patients undergoing CAC imaging and their clinicians to know how their score compares to others of similar age, sex, and race/ethnicity. In 2006, McClelland et al^[7] provided clinicians with a calculator to estimate an individual’s age, sex, and race/ethnicity-based CAC profile by comparing them with a database of 6,110 subjects aged 45–84 years from the MESA (Multiethnic Study of Atherosclerosis) study who did not have known ASCVD or diabetes. In this issue of the Journal of the American College of Cardiology, Javaid et al^[8] utilized CAC values from 3 populations younger than those in MESA to develop a calculator for individuals aged 30–45 years. The 3 populations totaled 19,725 predominantly White and Black individuals and included participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study,^[9] the CAC Consortium cohort,^[10] and the Walter Reed Cohort.^[11] Each cohort was weighted equally, and the authors smoothed the raw data to prevent overfitting, using a method similar to that of McClelland et al.^[7]

These 3 populations include the bulk of U.S. White and Black 30- to 45-year-old patients in published CAC datasets. As the authors note, their risk factor prevalence is similar to that of National Health and Nutrition Examination Survey participants. The CARDIA dataset was community-based, CAC Consortium participants were self or physician referred, and the Walter Reed Cohort was physician referred, although it was in a medical setting in which CAC testing was widely encouraged. Typically, physician-referred individuals would be expected to have a greater risk factor and thus CAC burden. On the other hand, individuals who would enroll in a study such as CARDIA are potentially subject to healthy study responder bias. Both calculators intersect at age 45 years, at which point CAC scores at each percentile are only slightly higher in the young adult than the MESA calculator. On balance, the authors succeeded in assembling a dataset and a calculator that is generalizable to the U.S. White and Black populations.

An important implication of the young adult calculator lies in its potential clinical utility. Should young adults aged 30–45 years be considered for assessment of CAC, and if so, who? The 2018 American Heart Association/American College of Cardiology/multisociety guideline for cholesterol management^[12] recommends consideration of CAC scores to further inform treatment decisions beyond risk-scoring and risk-enhancing factors. This recommendation, however, is based primarily on adults aged ≥45 years in MESA in which a CAC score of >100 identified those with a favorable net clinical benefit for statin use.^[13] Such an analysis is not available for younger adults, nor is the guideline recommended Pooled Cohort Equation score for 10-year ASCVD risk calculation applicable to those aged <40 years.

Although universal screening for CAC in young adults should not be endorsed, we suggest certain “CAC benefit groups” in which ASCVD risk may be sufficiently high to warrant assessment of CAC assessment from a shared-decision discussion between clinician and patient, including consideration of other risk enhancing factors. These groups include the following: 1) those with suspected or diagnosed familial hypercholesterolemia; 2) those with a family history of premature ASCVD; 3) those with multiple risk factors; and 4) those aged 40–45 years who are identified as borderline-intermediate risk by the current Pooled Cohort Equation.