Improving Prediction to Improve Prevention


All scientific discoveries, large and small, start with one common goal—to advance knowledge, be it about our bodies and health, our environment, or even our universe. But the most exciting discoveries, built on years of research and collaboration, fundamentally change how we understand our world.

In a special summer series, we'll talk with six Northwestern scientists whose work is already changing their fields, and could potentially change our lives.

Philip Greenland, Harry W. Dingman Professor and senior associate dean for clinical and translational research, has been studying how to better predict and prevent heart attacks for more than 15 years. He and his collaborators have found that CT scans –  imaging tests for the heart – could be the key to spotting blockages before they do too much damage. Science in Society talked to Greenland about the promise of this scan and the patients who might benefit from it the most. 

Philip GreenlandPhilip GreenlandTell me about the focus of your work.

We’ve been working for quite a while now on ways of improving how we predict who is likely to get blockages in their arteries. Blockages lead to heart attacks in some cases, sudden death in some cases, and often times there’s no warning, no symptoms that occur beforehand. So there’s great interest in trying to understand the factors that lead to heart attack or sudden death, and also great interest in understanding how to identify individuals who might be at particularly high risk. 

When we started working in this area, I would say about 15 years ago, we already knew that there were several major factors that underlie arterial blockage – high cholesterol, high blood pressure, cigarette smoking, diabetes, etc. And we believed that newer factors that were being discovered, things like clotting factors, inflammatory factors, and possibly genetic factors, would be helpful in identifying high risk.

We also thought there was going to be a role for what you might call early detection – identifying people who are starting to develop blockages by some sort of imaging test, something on the equivalent of mammography for breast cancer detection. If we could detect the arterial blockage building up early, that would be a possible signal that this person is already developing the disease that we’re concerned about – an early warning sign.

What have you and your colleagues found?

We’ve conducted a lot of studies now, over the last 15 years, on these different factors – clotting, inflammatory and genetic factors – as well as some imaging tests, looking at early, early evidence of arterial blockage. It turns out that one of the strongest signals we’re getting is that the traditional risk factors we knew about 15 years ago – cholesterol, blood pressure, and so on – keep getting confirmed again and again and again. So even though we keep looking for new factors that might add predictive information, once we take account of the old standbys, a lot of the newer factors aren’t turning out to be particularly helpful.

That would be a complete downer if it weren’t for the fact that the imaging studies are really starting to emerge as high impact in terms of improving prediction. It’s starting to look like it could really make a difference in patient outcome.

An image from a heart CT scan. The bright white spots visible in the heart (the grey organ in the top center of the image) are calcified plaques. (Image courtesy of Philip Greenland)An image from a heart CT scan. The bright white spots visible in the heart (the grey organ in the top center of the image) are calcified plaques. (Image courtesy of Philip Greenland)Could you tell me more about the imaging tests?
The study that’s turning out to be the most helpful is the CT (computing tomography) scan. In lay terms, people refer to this as a heart scan. It’s a very rapid scan, it can be completed in five to ten minutes, and generally it has a pretty low radiation exposure – about the equivalent of two mammogram exposures. But, unlike mammogram, which people tend to recommend yearly, the CT scan for the heart could probably be done much less frequently than that – no more than once every five to ten years. So, over a lifetime, the radiation exposure would be pretty low.

What kinds of people do you anticipate the test benefitting the most?
The patient populations we’ve been looking at are predominantly healthy people who have no symptoms, because that’s where we really think the biggest impact of early detection would be. People who already have symptoms have other reasons for doctors to pay attention to them. But the area where we think there is the greatest potential is people who otherwise wouldn’t get a whole lot of attention.

It turns out that those risk factors I was talking about earlier – high blood pressure and cholesterol –are pretty good at identifying high risk people and low risk people, but there’s a very large segment of people who fall in between. What we call “high risk” only accounts for about 10-15 % of heart attacks. Most of the heart attacks are occurring in people who have what you would call moderate risk. And, more than 50% of the population would be categorized as moderate risk.

So [this creates] a big dilemma. You either end up having to treat an enormous number of people with preventive-type drugs, or you need to find a test that would be able to further differentiate people from that moderate risk pool to people that are really high risk and people that are really low risk. And this CT scan, at least in terms of the research we’ve done so far, looks like it’s the best test out there for reclassifying, from this moderate risk pool, about 25% of them into the high risk category and about 15% of them into the low risk category.

What’s the next step for this research?

We’ve demonstrated that we can substantially improve prediction, so I’m at the stage of the research where I can say that it looks like it would make a difference. My guess is that this will be fairly rapidly adopted into practice guidelines, based upon what we’ve seen in the past.

The next step in our research is a clinical trial that would really nail this down, which is where we’re headed in the next phase. There are important questions [to answer], because what we’re talking about is a test that adds a moderate cost – probably in the range of $200 for the test itself – but that’s not its only effect. It may lead to additional testing, and it also has a fairly big impact on lifelong drug therapy decisions.

When did you decide to pursue science and medicine as your career?
I decided that I wanted to go into medicine pretty early in my life, but I didn’t decide I wanted to do “science” until my cardiology training. I was seeing a lot of people who were relatively young – let’s say forties, fifties and sixties – who were getting heart attacks. This was during the time that the heart attack rate in the United States was peaking, and it seemed to me that we, as a profession, needed to do something more aggressive about that. [We needed] to better apply what we already knew about things like cholesterol and blood pressure and so forth, and I think we have since then. At the same time, it became clear to me that there was a lot more that we still didn’t know. And I wanted to really be a part of the answer to that.

What advice do you have for young people in choosing a career?
I think that medicine is a very exciting career. We don’t emphasize enough to younger people the research opportunity within medicine. What you see written about in the newspapers all the time these days is about the complexity of medicine, the challenge of paying for medicine and healthcare costs and all of that sort of thing. But I think the exciting aspects of medicine are, for most people, in one of two areas. And hopefully for a lot of people it’s both areas. One is the really valuable, one-on-one interaction with patients, which provides a great deal of satisfaction – you can see on an almost daily basis that you’ve been able to help somebody.

[The second] is the exciting opportunity you have over a career to make a big impact on how medicine is practiced, and how the practice of medicine can be improved. With the improvements in technology and the improvements in our understanding of basic biology, the opportunities that young people would have to really make an impact – to find a cure for the incurable diseases, or to find technological solutions to problems like congenital disease or horrible injuries – are great. So I think it’s one of the most exciting things you can imagine doing that would really help mankind.


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