More Research Suggests CTA-Detected Vulnerable Plaque May Predict ACS Development

Deborah Brauser

July 21, 2015

TOYOAKE, JAPAN — Coronary computed tomography angiography (CTA) may be useful in determining whether patients who present with chest pain will develop acute coronary syndrome (ACS), new research suggests[1].

An observational study of more than 3000 patients showed that CTA-detected high-risk coronary plaque (HRP) characteristics were an independent risk factor for developing ACS up to 4 years later. In addition, plaque progression, as tracked by CTA scans a year apart, also predicted ACS.

Although "the cumulative number of ACS patients" without HRP was similar to those with plaque (40 vs 48, respectively), the percentages were 10 times lower (1.4% of 2864 patients vs 16.3% of 294 patients), according to first author Dr Sakako Motoyama (Fujita Health University, Toyoake, Japan) and colleagues. Plus, "all but two patients with no plaques at all were free from ACS."

"However, non-HRP lesions also developed ACS, and serial analysis revealed the plaques that progressed over time on a volumetric basis and evolved from non-HRP to HRP were the ones more likely to result in ACS," they write in the article, published July 28, 2015 in the Journal of the American College of Cardiology.

Coinvestigator Dr Jagat Narula (Mount Sinai Medical Center, New York, NY) told heartwire from Medscape that he was "very excited about the prospects" of the study. "I think this is one of the most comprehensive papers on the topic," he added.

Dr Eugene Braunwald (Brigham and Women's Hospital, Boston, MA), who wrote the accompanying editorial[2], said to heartwire , "They showed that a small number of patients had abnormal plaques and a high risk of heart attack. The results mean that while this is useful to detect patients who are high risk, the majority of patients are not high risk and still liable to have a heart attack.

"Finding a high-risk plaque is very helpful. But not finding a high-risk plaque doesn't give you a free pass. You may well have ACS later, but the chances are much lower."

Focus on the Whole Disease

The investigators previously examined whether HRP, verified by CTA, could predict ACS over 2 years in 1059 patients. They found that 15% of those with HRP, 0.5% of those without HRP, and 0% of those without any plaques developed ACS. In the current study, they wanted to examine these issues in a much larger patient population.

Of the 3158 patients (70% men; mean age 66 years) evaluated, all of whom underwent CTA in Japan between March 2003 and May 2011, 294 had HRP. Both fatal and nonfatal ACS were tracked during a mean follow-up of 3.9 years.

In patients who developed ACS, "the culprit lesion was found in the right coronary artery in 40 patients, left main trunk in four patients, left anterior descending artery in 37, and left circumflex coronary artery in seven patients," report the researchers.

A total of 51% of patients with HRP-positive and 49% with HRP-negative lesions went on to develop ACS. Among those with positive lesions, 40% developed ACS 1 year later and 69% by the 2-year mark.

Of those with two feature-positive plaques, 23% developed ACS, as did 10.7% of those with one feature-positive plaque (P<0.0001 for each group vs those with no plaque).

In addition, 659 of participants had significant stenosis (SS), defined as at least 70%. In these patients, 5.5% developed ACS vs 2.1% of those without SS (P<0.0001).

More of those patients with HRP and SS and those with HRP without SS had ACS (18.8% and 14.9%, respectively) vs patients without HRP with or without SS (1.2% and 0.6%, respectively).

Finally, an additional analysis measured plaque progression with CTAs 1 year apart in 449 participants followed a mean 4.1 years. It showed that 56 patients had plaque progression. Of those with HRP at the first CTA scan and plaque progression, 27% developed ACS—as did 10% of those without HRP but with plaque progression.

Narula said that the two main takeaways from the study are that it's possible for CTA to detect HRP and that, because ACS was detected in both those with and without HRP, "we must focus on disease progression and prevention. This study highlights the importance of looking at the disease and patient as a whole, and not just at one single plaque."

"More Complicated"

Braunwald wrote the accompanying editorial for the investigators' earlier study as well as the current one[2]. He told heartwire that he was impressed by the progress the researchers have made.

"This is a very important subject: Can you, without doing catheterization, detect these very serious lesions that are likely to cause heart attacks? These investigators have much more information now. I complimented them on the first paper but said they needed to do more. And I was glad to see that they did more," he said.

Braunwald likened the new results to 100 participants in a motorcycle race. If five of the 10 who drive over 150 mph crash, they would be at higher risk percentagewise than the five of 90 who crash while driving somewhat slower. But although the risk is lower in the slow drivers, they aren't completely out of the woods—they're just not as likely to crash as the speed demons.

"You're not saying this latter group is immune, but they are much safer," he said.

He added that the findings on plaque progression were also interesting. "Those who developed more plaques were at even higher risk, which tells me that the process is dynamic," said Braunwald.

"Taking one snapshot in time of a moving video can be helpful, but it doesn't tell you the whole story, as these plaques are coming and going. It shows that this disease is somewhat more complicated than we thought."

Important but Key Questions Remain

Dr James Min (Weill Cornell Medical College and Dalio Institute for Cardiovascular Imaging, New York Presbyterian Hospital, NY) agreed that this was "an extremely important" study that builds on earlier research. "It's one thing to show an association at the time of an event. It's another thing to be able to use it to prognosticate risk."

He noted that the findings also "open the door to an array of potential future investigations," including determining the role of these plaques in relation to culprit lesions at time of MI or ACS. "Are they the high-risk plaques that are actually causal of the future event? That is still a key question," said Min, who was not involved with the research.

Still, the investigators "found either a direct association or indirect surrogate of future adverse outcomes. So that's a big step forward, and the length of the study's follow-up certainly bolsters its strength," he said.

Min added that the study shows there's much more that can be derived from CT "than just stenosis severity. The atherosclerotic plaque features that can be characterized noninvasively really do offer an additional method for risk verification that we simply didn't have prior to CT."

Narula has received research support (equipment grant) unrelated to the current study from Philips and GE Healthcare. Disclosures for the coauthors are listed in the article. Braunwald reports no relevant financial disclosures. Min has received financial support from the National Institutes of Health.

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