Study Points to Ideal Age for CAC Testing in Young Adults

New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.

“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.

CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD) but routine screening is not recommended in low-risk groups. US guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.

The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.

The participants were free of clinical ASCVD or CV symptoms at the time of scanning, but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).

As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).

Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.

Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.

The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.

“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”

In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.

The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (e.g., smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (e.g., diabetes plus dyslipidemia).

Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dzaye said, “we very much believe that this can be used because for the process we published the internal validation and we also did an external validation that is not published at the moment in [the] MESA [trial].”

He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.

“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, told | Medscape Cardiology.

Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”

“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘we’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Greenland said.

An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”

Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”

Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.

“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Naqvi and Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.

Commenting to | Medscape Cardiology, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.

Sometimes smart scientists and researchers differ but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”

Blumenthal, who was not part of the study, noted that US guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.

“This study adds to the information about how to use that type of testing. So I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”

The study was supported in part by a research grant from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute. Dzaye, Blumenthal, Naqvi, and Polonsky report having no relevant financial relationships.

J Am Coll Cardiol. 2021;78:1573-1583, 1584-1586. Abstract, Editorial

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