Vascular Vulnerability

Detecting who’s at risk for heart attack or stroke before it’s too late

» Web extraIn 2007, a group of Canadian imaging researchers decided that they needed to establish a national network that could streamline the process of how images were acquired, stored and analyzed. Such a network could also facilitate large, multicentre studies. Thus the Canadian Atherosclerosis Imaging Network (CAIN) was born.
Read about Moody’s work with CAIN in Image This!

In the labyrinth beneath Sunnybrook’s main building, Dr. Alan Moody confidently navigates his way down empty corridors and through unmarked doorways. Overhead, there is an exposed network of pipes—complex, interconnected and not unlike the intricate web of blood vessels supplying the human body. For Moody, head of the vascular biology imaging research group at Sunnybrook Research Institute (SRI), it’s a fitting place to study the body’s circulatory system and its role in disease.

On the surface, heart attack and stroke might seem like different diseases. Strip away their façades, however, and they are essentially the same disease manifested in different organs. “The poster children for cardiovascular and neurovascular diseases are heart attack and stroke, respectively,” says Moody, who is a senior scientist in the Schulich Heart Research Program at SRI. “The underlying vascular disease is the same for both. The differences are purely anatomical.”

Vascular disease describes any condition that affects the blood vessels in the body. Atherosclerosis, in which plaque builds up inside the arteries, is of particular interest to Moody. Plaque is primarily made up of fat, cholesterol and calcium. Over time, as it accumulates on the artery wall, plaque hardens and narrows the artery to restrict blood flow.

But not all plaques are created equal. Whereas traditional risk assessments focused on how much plaque is in the arteries, scientists now appreciate that the type of plaque is as important. So-called “vulnerable plaque” is more likely to create complications than others.

“We know that the plaques that rupture and cause clinical events are often not the ones that cause the greatest obstruction in the artery,” says Dr. Anna Zavodni, a radiologist and affiliate scientist in the Schulich Heart Research Program. “It’s really a combination of the volume of plaque as well as the characteristics of that plaque.”

Building on that idea, Moody and Zavodni are using magnetic resonance imaging (MRI) to determine whether plaque structure and composition can predict cardiovascular outcomes. The benefits of MRI are that it is noninvasive and can provide enough resolution and detail to allow scientists to detect features like a plaque’s fat-filled core.

We already know what to do with the symptomatic patients. The bigger question is, what do we do with the asymptomatic ones?

As described in a recent paper published in the journal Radiology, Zavodni and colleagues recruited 946 adults as a part of the Multi-Ethnic Study of Atherosclerosis (MESA) to determine if measuring vulnerable plaque components within the carotid arteries can predict the risk of a cardiovascular event such as heart attack, angina or stroke. None of the participants initially had symptoms of cardiovascular disease. In addition to a physical examination and blood tests, everyone underwent MRI to look for vulnerable plaque and changes in the artery wall.

During the five-and-a-half-year follow up, people whose plaques contained higher levels of fat or calcium, or who had thicker artery walls, were more likely to experience an adverse cardiac event. Further, plaque composition was as good a predictor of cardiovascular disease as were traditional risk factors like cholesterol, blood pressure and smoking.

MESA is the first prospective population study to examine the usefulness of plaque characteristics in predicting cardiac events. One of the strengths of the study lies in its ethnic diversity, but MESA’s real value is that all of the participants were “heart healthy”—they had never had a heart attack or stroke.

Zavodni points out that for 25% to 50% of patients who experience a heart attack for the first time, this is their first presentation of heart disease. “Most people don’t even know they’re sick until they experience this massive, life-altering event,” she says. “Being able to look at a population and decide who needs very aggressive treatment versus who can be left alone, that’s important.”

In another study, Moody and Zavodni asked whether they could assess cardiovascular risk based on intraplaque hemorrhage (IPH), a feature of advanced and unstable plaques. Moody became interested in IPH when he found that patients with it in their carotid artery were six times more likely to have a neurovascular event than those without it. Given the similarities between cardiovascular and neurovascular diseases, he wondered whether IPH might also predict cardiovascular events.

Dr. Anna Zavodni is lead author on a study that examines whether plaque characteristics can be used to predict heart attack in people without symptoms.

Photo: Courtesy of Dr. Anna Zavodni

By reviewing patients’ charts, the researchers found that nearly three times as many patients with IPH in their carotid artery had experienced a prior adverse cardiac event than patients without it. This was a surprising finding because the carotid artery supplies blood to the brain, not to the heart. Their results also showed that the presence of IPH is a stronger indicator of risk for cardiovascular disease than risk factors like gender, age and smoking. Dr. Navneet Singh, a radiology resident at the University of Toronto, led the study, which was published in the International Journal of Cardiovascular Imaging. The team concluded that IPH might serve as a useful marker of systemic vascular disease that includes the brain and the heart.

Having established the usefulness of MRI in detecting features of vulnerable plaque, Moody’s group is trying to define criteria by which patients should be screened. As he is quick to note, they are not advocating for all patients to undergo MRI screening. “We’re trying to hone down the numbers [of patients] and look at the cost-effectiveness,” he says.

Moody is also chair of the department of medical imaging at the University of Toronto and a member of the steering committee for the Canadian Atherosclerosis Imaging Network (CAIN). He is leading a study of more than 400 patients that is examining the ability of MRI to characterize plaque in the carotid artery supplying the brain and therefore predict clinical outcomes for neurovascular disease.

Moody and Zavodni’s research underscores the need for better tools to identify people before they become patients. These individuals often show no signs of cardiovascular or neurovascular disease, but nonetheless may be at risk.

“We already know what to do with the symptomatic patients,” says Moody. “The bigger question is, what do we do with the asymptomatic ones?”

“The more imaging tools we have, the better we’ll be able to separate patients along meaningful lines and figure out which of those patients need repeated follow up, who will benefit from an early preventive surgery, and who will be fine with a few changes to their lifestyle,” says Zavodni.

Moody’s research is funded by the Canada Foundation for Innovation, Canadian Alliance for Healthy Hearts and Minds, Canadian Institutes for Health Research, Heart and Stroke Foundation (HSF), and Ontario Ministry of Research and Innovation. Zavodni’s research is funded by the HSF, National Institutes of Health and Radiological Society of North America.