April 25, 2013
Cardiovascular disease is the most common cause of mortality in the U.S. It is thus, almost by definition, a major topic of concern for the HIV-infected people we count among our patients and clients -- many of whom are intimately associated with traditional cardiovascular risk factors, such as cigarette smoking, low physical fitness, hyperlipidemia and hypertension.
Yet when it comes to the incorporation of cardiovascular risk management into HIV care, we haven't seen much in the way of consistent or comprehensive guidance. As we accumulate more data regarding the intersection of HIV and cardiovascular disease, a clearer picture of the issue is developing. But that picture has yet to be properly framed for many of the health care professionals who actively treat people infected with HIV in the U.S.
For this episode of HIV Management Today, we called in an expert to paint -- and frame -- that picture for us. David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC), the site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, and the director of the North Carolina AIDS Education and Training Center. He is a widely respected clinician-researcher who has extensively spoken and conducted research on cardiovascular complications in HIV-infected populations.
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Dr. Wohl, how has our knowledge regarding the relationship between HIV and cardiovascular risk deepened over the past several years?
I think our understanding has evolved, and the ways that we've come to understand things have been informed by more and more data.
There are a lot of disease states where they have these large cohorts of people. If you're talking about diabetes, hypertension, cardiovascular disease, cancer: You can look at these large cohorts of people who get these diseases because they're fairly prevalent. For a long time, we didn't have that with HIV. But we've got more and more of that.
On the other side, in addition to these relatively large cohort studies that we now can enjoy within the context of HIV, we have more and more pathogenesis studies -- studies that look at what is going on at the level of the blood vessel, and what the connection is between humeral markers, inflammation markers, traditional risk factors and novel, putative risk factors for cardiovascular disease.
What we've come to understand is: It's not as simple as we may have thought, where you take drug X for your HIV, that raises your lipids, and thus your risk for heart disease is higher. It's much more complicated: There may be some action of that drug on your cardiovascular risk, but what about the virus itself? What about the underlying immune activation that occurs in anyone who is HIV infected, to some extent -- some people more than others? How do you tease that apart from this higher prevalence of traditional risk factors that we see among people living with HIV -- where, instead of 20 percent of people smoking, 60 percent of HIV-infected people smoke? And hard living: What about cocaine? There are a lot of these hard-to-measure confounders.
I think our understanding has now encompassed an appreciation that this is pretty complicated and multifactorial, and that there's not a single line that you could connect from risk factor to risk in the HIV-infected person.
It feels like you just opened seven or eight different cans of worms. As disgusting as it is to explore worms, it would be really nice to examine those more closely. Let's start by focusing specifically on what we're talking about when we say "cardiovascular risk": What particular risks, and clinical manifestations of those risks, are we talking about when we talk about people living with HIV?
For some, it can be a composite between having a heart attack and a stroke; having to have some intervention to open up a blocked artery, such as angioplasty; or, even some definitions include peripheral vascular disease, peripheral artery disease. There are different ways to slice it.
In the purest sense -- maybe in the most absolute -- it's whether or not there's a myocardial infarction, a heart attack. Because you either have one or you don't have one.
What is our current knowledge regarding the relative risk of MI in HIV-infected people compared with the population as a whole?
Looking at heart attack and cardiovascular disease, in general, we see that people with HIV tend to have more than you would expect, even when you account for a higher prevalence of traditional risk factors. When you try to get rid of the confounding of more smoking, age and gender, things like that --
Some do correct for that, and some don't. I think that's an important point that I'd like to get back to, because I think that it is hard to account for every single confounder. That's sort of this lingering question.
But you do see multiple studies coming from multiple places, done in multiple ways, that are pretty much coming out with a fairly consistent picture of a somewhat higher risk [of MI among HIV-infected people].
The good news is -- you can look at this as the glass being half full or half empty -- but the good news is, this is not like a huge, amazing, oh-my-God-everyone's-going-to-get-a-heart-attack kind of increase in risk. It is almost like HIV is another risk factor.
There's a lot of other risks that exist, and quantifying this risk depends upon which study you look at. Some of the more recent studies are showing that the risk is there, but it's not whopping: There's a slight to a moderate risk increase among people living with HIV for this to happen, but it still is a fairly rare or unusual event in people living with HIV, especially the middle-age range.
When you get older, all of us have an increased risk for cardiovascular disease; and it becomes much more prevalent. This is where we start to see the difference. We see younger people with HIV not really having as much risk. After about age 40-plus is where you start to see more of this excess risk. I think that's intriguing, as well.
Are those parallel curves? If you're comparing HIV-infected to HIV-uninfected populations and you're watching the MI risk or cardiovascular disease risk as people age, do they increase at the same rate? Or does the rate of, let's say, MI among HIV-infected people increase at a faster rate as people age?
Some of the trend data that we saw most recently are from the D:A:D cohort, the large European cohort. That includes only people living with HIV. And when they compared coronary heart disease from age 40 onward to other cohort data, you can see that there may be an increased excess, but it's fairly parallel to most of the data from other cohorts.
So, you do have this higher relative risk. But, over time, it doesn't seem like there is an accumulation of even greater piling on of excess risk over time, such that they splay divergently.
I think what we are seeing is this increased excess risk during the early part of middle age that may be increasing because it started where there was really no excess risk, but hit some sort of a plateau, where you start to get higher rates but they don't seem to be wildly accelerating.