Thoracic Aortic Calcium Adds Prognostic Value to CAC Score

BOSTON, MA—The presence of thoracic aortic calcification (TAC) is independently associated with adverse outcomes, even after accounting for the degree of coronary artery calcification (CAC), which is already a powerful tool for risk stratification, according to two analyses out of the Multi-Ethnic Study of Atherosclerosis (MESA).

In one study, reported by Venkat Manubolu, MD (Harbor-UCLA Medical Center, Lundquist Institute, Torrance, CA), TAC was associated with greater risks of coronary heart disease events and all-cause mortality, although the analysis did not adjust for the degree of CAC.

However, in the second, reported by Alexander Razavi, MD, PhD (Emory University School of Medicine, Atlanta, GA), greater TAC burden was associated with greater risks of overall CVD and all-cause mortality after adjustment both for traditional cardiovascular risk factors and CAC.

The two studies were presented here at the 2023 Society of Cardiovascular Computed Tomography (SCCT) meeting.

Commenting for TCTMD, Rene Packard, MD, PhD (UCLA Health, Los Angeles, CA), who moderated the session at which Manubolu presented his results, said, “We’ve known for a long time that the more calcification you have, the more underlying atherosclerosis you have, and that obviously is associated with a higher risk, if not on statins in particular.”

These studies look at calcification at the level of the thoracic aorta in a more-complete way than previous analyses, but having additional information on TAC generally won’t change patient management guided by CAC scoring, Packard said. “You want to put them on maximal medical therapy regardless of whether or not they have thoracic calcifications if they have underlying coronary artery calcifications.”

The exception would be patients with no coronary calcification considered to be at low cardiovascular risk, Packard said. “If when looking into the thoracic aorta systematically you’re able to quantify thoracic calcification that you otherwise would have missed, that puts them in a different category, and that—for me at least—would be enough of an entry point to put them on a statin or another lipid-lowering medication.”

Razavi noted that TAC often is not included on clinical CAC score reports, adding, “We believe that these results support the regular reporting of TAC on noncontrast cardiac-gated CT scans to guide risk stratification and ultimately preventive therapies.”

Assessing TAC

The degree of CAC is well established as a predictor of cardiovascular events and has been adopted by practice guidelines as an option for risk stratification in intermediate-risk patients. But the impact of calcification outside the coronary arteries has not been as well studied.

Both studies presented at the SCCT meeting focused on TAC, the most common type of extracoronary calcium, and used data from MESA, a prospective, population-based study conducted in six US cities that included more than 6,800 individuals ages 45 to 84 who were free of clinical CVD at baseline in 2000-2002.

The analysis by Manubolu and colleagues included 2,797 participants who had not had a coronary heart disease event prior to undergoing a chest CT scan as part of the MESA’s fifth examination in 2010-2012.

The investigators formed four TAC score categories: 0, 1-100, 101-300, and > 300. Across increasing categories, mean age rose from 62 to 74 years and the proportion of men declined from 59% to 46%. Overall, 94% of participants had some degree of TAC.

Through a median follow-up of 8.7 years, the presence of TAC was associated with greater risks of coronary heart disease events (HR 1.13; 95% CI 1.01-1.27) and all-cause mortality (HR 1.11; 95% CI 1.04-1.18).

But what this really does is to maximize the amount of information that can be extracted from these CTs and CT angiograms, and then that ultimately helps us risk-stratify our patients better. Rene Packard

“Quantification of TAC may offer additional prognostic value at no additional cost or radiation exposure from the existing chest CT scans,” Manubolu said, acknowledging, however, that the analyses did not factor in the degree of CAC. “In future studies, if the TAC consistently proves to have incremental prognostic value in addition to CAC or in patients with CAC 0, this may potentially call for [a] change in the current calcium-scoring protocol [to] include the thoracic aortic arch in the calcium-scoring protocol.”

Razavi’s presentation provided insights into the added value of TAC on top of CAC burden. His group’s analysis included 6,870 MESA participants (mean age 62.1; 53% women) who underwent cardiac CT at the first study visit and were followed for a median of 17.4. with outcomes stratified according to three TAC score categories—0, 1-499, and ≥ 500—and four CAC score categories—0, 1-99, 100-299, and ≥ 300.

After adjustment for demographics, traditional CV risk factors, medications, and CAC as a continuous variable, patients with the highest burden of TAC had significantly greater risks of overall CVD (HR 1.25; 95% CI 1.04-1.51) and all-cause mortality (HR 1.42; 95% CI 1.23-1.62), with nonsignificant trends in the same direction for coronary heart disease (HR 1.24; 95% CI 0.98-1.57), stroke/TIA (HR 1.26; 95% CI 0.93-1.71), and heart failure (HR 1.30; 95% CI 0.96-1.76). Relationships tended to be stronger in patients with no CAC, which encompassed about half of the cohort.

Within each of the four CAC categories, the risk of adverse outcomes tended to increase in a stepwise manner with higher levels of TAC. The researchers found that adding TAC to the CAC-Data and Reporting System refined risk stratification in terms of all-cause mortality.

Use All the Info From CT

Razavi said one of the reasons TAC is not routinely reported along with CAC scores is that the quantification of TAC—unlike CAC—is not automated. He said his team hopes to develop an algorithm to automate reporting and measurement of TAC.

This could influence patient management because the MESA data show that TAC is more important in women than in men, with women more likely to develop TAC before coronary calcium. By measuring TAC, “we may be able to catch more women earlier on in the biological process of arterial calcification and ultimately guide preventive therapies earlier for women,” Razavi said.

Moreover, there is a group of individuals with high levels of both TAC and CAC who have a very high risk of adverse outcomes, Razavi said, noting that such extreme risk would not be captured with the CAC score alone. “They may ultimately be able to be put on combination lipid-lowering therapy and more-intense preventive therapy.”

For Packard, what these and other studies indicate “is to use the totality of the data that is available to us during the CT that we sometimes don’t use,” particularly since there is little downsides to doing so.

“There’s no change in protocol, there’s no change in radiation, there’s no change in iodine contrast material exposure,” he continued. “But what this really does is to maximize the amount of information that can be extracted from these CTs and CT angiograms, and then that ultimately helps us risk-stratify our patients better.”