An Interview With David Alain Wohl, M.D.
A major study published recently in the Annals of Internal Medicine has reinvigorated discussion about the link between cardiovascular disease and HIV. Not that the debate over the complex interplay between HIV and heart health had been dissipating -- if anything, it's one of the hottest areas of HIV research, dovetailing with issues ranging from inflammation to senescence.
What sets this new research apart, however, is its scope and sheer gravitas: It's a solidly constructed, cross-sectional investigation of roughly a thousand participants in the storied Multicenter AIDS Cohort Study (MACS) conducted by Wendy Post, M.D., of the Johns Hopkins University School of Medicine, and colleagues. What's also notable about this new research is the way in which its findings were quickly misinterpreted.
To drill down into the data and tease out the real clinical implications, our research editor Warren Tong spoke by phone with David Wohl, M.D., an associate professor of medicine at the University of North Carolina School of Medicine and the co-director of HIV services at the North Carolina Department of Corrections.
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Clarifying the Point of the Study
David Alain Wohl, M.D.
To summarize this research: They went through the MACS cohort and pulled about a thousand individuals, 600 HIV infected, 383 uninfected; and they found a higher risk of coronary artery disease in the patients living with HIV, as opposed to those who were not.
Some of the headlines have been characterizing the new study as showing that there's more heart disease in people living with HIV than people without -- and in this case, when we're talking about "people," we're talking about male people, not female people. Because the MACS cohort is just men.
I think we have to be careful, because what they're looking for is plaque. Plaque in the coronary arteries is atherosclerosis. It is not good for you. But many of us have plaque. About three-quarters of the men in the MACS cohort -- these are HIV-positive men and HIV-negative men, all men who have sex with men [MSM] -- about three-quarters had plaque. So, plaque is not abnormal, if you think about it as part of the normal aging process.
We all get plaque eventually. It doesn't necessarily mean that these people had, quote-unquote, heart disease.
The thing that they did do that, I think, makes this study really important and unique is that they looked for the different types of plaque. Previously we've had studies that have been pretty small -- rigorously done, but small. This study was rigorously done and had a lot of people. I think there are some big take-home messages from this study because of those advantages, compared to other studies that have been done.
Can you go over the different types of plaque that they were looking for?
There are concerns about plaque in general. But we've talked a lot in the past about calcified plaque. Those are plaques that are harder. There's calcium in them. Calcium, as we know, is a mineral that's in our bones. When we do CT scans and look for calcium in the heart, we can see those plaques light up. That's done not-uncommonly in the general population; you get these CT calcium scores. They've been used for a while to add more information about the propensity for people to have a heart attack, above and beyond what we can get with the EKG or even a stress test.
But there are other types of plaque that don't show up so well. These are uncalcified, or noncalcified, plaques. These are softer. They are considered more vulnerable to rupture. And when they rupture, they send debris downward -- just like a frozen river [that] starts to thaw. Some of that ice is going to go downstream, and if you start getting it into the small tributaries, they can block flow. That's what's going to happen in the heart. When we block flow, the muscle dies -- in this case, heart muscle.
What they were able to do [in this study] is look at calcified plaque, uncalcified or noncalcified plaque, and mixed plaque, based upon how it looked on the imaging studies. A subgroup of people actually did have calcium scores done from the larger group, and they compared them between the HIV-positive and HIV-negative people.
Some big take-homes: One is, even in this population of gay men living in major metropolitan areas in the United States, there were differences between the HIV-positive and HIV-negative men, just in their general characteristics. Some people generally think that the MACS cohort is homogeneous. It isn't.
Even in this cohort that's refined, if you will, to a certain group of people, being HIV positive carried with it additional risk factors for cardiovascular disease that had to be adjusted for. So it's not like you just enroll men who have sex with men in these areas, and the HIV-positive and HIV-negative men are going to be the same. Being HIV positive is often associated with other risk factors of cardiovascular disease: lifestyle risk factors.
That's one thing that I think is important. It's better; it's closer than in a lot of other studies. But there are still differences that had to be adjusted for. Which is fascinating to me, because I do think people with HIV generally have had different types of lives -- not everybody, but oftentimes -- compared to HIV-negative people.
Major Findings: Differences in Plaque Driven by HIV Status, Age
Going to the data itself: After adjusting for those factors, what we saw was that you were more likely to have uncalcified plaque, which we said may be more vulnerable to rupture, if you're HIV positive. It's about one-and-a-half times the risk of having vulnerable plaque, if you're HIV positive versus HIV negative.
But there were other factors that, when you start adjusting for cardiovascular risk in demographics, became less significant -- borderline significant, is what they said -- and that's with calcified plaque, or plaque overall. There's clearly a signal.
Fascinating to me, however, was that when we looked at where the plaque occurred, as far as the age spectrum, what we saw was a really interesting pattern: For the HIV-negative men, over time, they started to get more and more calcified plaque, and less of the noncalcified plaque; whereas, for HIV-positive men, the calcification was less likely to occur later on in age, but the vulnerable, noncalcified increased.
There were differences that you can see throughout the age spectrum, but they were really more profound in people 65 and older, HIV positive versus HIV negative. I think that probably drove a lot of the statistical difference between the groups.
Putting that into more simple words, what it means is that the difference that was seen between HIV-positive men and HIV-negative men, as far as these noncalcified, vulnerable plaques, was more profound in men who are 65 and above, and was driven largely by the decrease in vulnerable plaques that we saw in the HIV negatives, while we saw an increase in the HIV positives. And when we have one group that's going down and one group that's going up, that leads to a bigger chance of finding a significant difference than if one group stayed stable and the other one changed.