Matters of the Heart: The Emerging Field of Environmental Cardiology

April 13, 2005
2:00 pm US Eastern Time

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Call Transcript

1. Welcome: Michael Lerner, PhD, President, Commonweal

This is a wonderful and important call, today. I just want to start with a personal anecdote. I had a heart attack 20 months ago, at the age of 59, after many years of eating a healthy diet and living in the country. My body burden, which was tested by the Environmental Working Group, was distinguished by having very high arsenic and high mercury. So it’s an interesting call for me, because our presenters are going to be discussing, among other things, the role of arsenic and mercury in cardiovascular disease. And now Jeanette Swafford will introduce the call.

2. Introduction: Jeanette Swafford, MHEd, Director of Health Initiatives, Collaborative on Health and the Environment

Thank you Michael. This is an exciting topic. I have to say that the more I’ve learned about it, the more engaged I’ve become. Today’s speakers will provide a broad overview of the sciences area. We’re lucky to have some specialists with us who are really at the forefront of work in environmental cardiology.

The call will begin with Dr. Ted Schettler, who’s the Science Director of the Science and Environmental Health Network. Dr. Schettler coordinates CHE Science Working Group, and he’s also the author of the peer review paper on heart disease, entitled, Heart Disease and The Environment, which is a summary of the evidence. For those who haven’t seen that, this is a great resource that combines a lot of what we’ll be discussing, today.

Dr. Schettler will introduce the areas of environmental cardiology, and discuss the recent research on arsenic and its relationship to heart disease. He calls arsenic the “sleeper.” So I’m particularly interested in this piece of the presentation.

Next we’ll hear from Dr. Eliseo Guallar—all the way from Spain, originally. Dr. Guallar is assistant professor of epidemiology and public health. He’s also the associate editor of the Annals of Internal Medicine, and of the American Journal of Epidemiology. Dr. Guallar’s work focuses on epidemiology and the prevention of cardiovascular disease, with a special emphasis on heavy metals. Today he’ll talk about the work with mercury and heart disease.

Finally, we’ll hear from Dr. Murray Middleman, who is a cardiologist and associate professor in the Department of Epidemiology at the Harvard School of Public Health, and an associate professor of Medicine at the Harvard School of Medicine. He’s also a co-author of the paper on Air Pollution and Cardiovascular Disease—the Statement for Healthcare Professionals from the American Heart Association. He’s interested in the triggers of acute cardiovascular events. He’s also studying the prognosis of premature acute coronary syndrome in women. Dr. Middleman will discuss air pollution and its connection to cardiovascular disease, today. He’ll also talk about the American Heart Association’s statement, as well as activities that have occurred since the statement was released last year.

With that, I will turn it over to Dr. Schettler.

3. First Speaker: Ted Schettler, MD, MPH, Science Director, Science and Environmental Health Network

Thanks, Jeannette. Good morning. Heart disease can be caused by birth defects, abnormalities of the heart muscle, the blood vessels, the heart valves and the conduction system that regulates the heartbeat. Rarely, the heart can actually be a site of tumors.

On this call, we’re going to focus primarily on atherosclerosis. There will be mention of rhythm disturbances and other causes of narrowing of the arteries. We won’t discuss birth defects here, but I’ll just point out to folks that there is a summary paper on this on the CHE website that does discuss cardiac defects to some degree.

Cardiovascular disease is the leading cause of death in the US—accounting for about 38 percent of deaths, and a primary or contributing cause in many others. According to the Centers for Disease Control, the proportion of premature deaths due to heart disease is greatest among American Indians and Alaskan Natives and Blacks, and lowest amongst Whites.

So-called “traditional” risk factors for heart disease include hypertension, elevated cholesterol, lack of exercise, overweight, obesity, smoking and diabetes. The likelihood of having two or more of those risk factors is highest amongst Blacks, American Indians and Alaskan Natives, and lowest amongst Asians. Other environmental factors can also play a role, and that’s what we’re going to focus on, today. They include air pollution, some synthetic chemicals, metals and drinking water quality. They all can cause or exacerbate pre-existing cardiovascular disease.

Among the synthetic chemicals, many organic solvents can predispose cardiac arrhythmias. These increased risks are usually associated with higher exposures that may occur in a poorly designed or ventilated workplace, and of course are relevant to those workers.

Among the metals, mercury, arsenic, cadmium, lead and cobalt have each been implicated in heart disease of one kind or another. I’m going to just briefly discuss arsenic. We’ll be hearing later about mercury—and others are covered in the summary paper on the website.

Arsenic exists in both inorganic and organic forms. Inorganic arsenic is generally more toxic than organic. Inorganic arsenic can be present in drinking water from natural sources, and is actually an important as a source of exposure for many people. Some areas have much higher levels than others.

Arsenic has also been commonly used as a wood preservative—in what was called CCA-treated wood. This can be a source of human exposure, from hand-to-mouth activity, in people who are playing in playgrounds made of that wood, or otherwise handling that kind of material.

Organic arsenic is commonly present in seafood. But organic arsenic is also used in large commercial poultry-raising operations, to prevent and treat parasites in these birds. As a consequence, chicken consumption has become a significant source of arsenic exposure in the general population. People who consume chicken regularly are exposed to arsenic from that source, alone—at levels that supply a substantial fraction of the tolerable daily intake, accordin to the World Health Organization.

Approximately 65 percent of the arsenic in chicken meat is actually transformed into the inorganic form. Then, to sort of round out the cycle, as the manure of chickens treated with arsenic is spread on the ground, the organic arsenic in the manure can be converted into inorganic form, and then leaches into the ground in surface water. So you can see how we’re needing to take a look at this issue from a much more ecological perspective.

High levels of arsenic in drinking water cause thickening of the walls of arteries, and are associated with a condition called Blackfoot Disease, which is prominent in Taiwan, where drinking water levels of arsenic can be very high. Progressively higher levels of arsenic in drinking water are also associated with cardiovascular disease. The coronary arteries are thickened, and mortality from cardiovascular disease is elevated in these populations. It’s been shown in Taiwan, and it’s been shown in Chile and other places where arsenic levels are high.

The threshold level of arsenic in drinking water associated with health impacts is not entirely certain. We do know that skin lesions and increased skin, lung and bladder cancer risks begin to appear at drinking water levels of 10 parts per billion. There are large populations of people who—even in the United States—are drinking water that has arsenic at those levels or higher. It may be the case that hypertension and circulatory problems actually begin occurring at lower levels than that. But the threshold, if there is one, is uncertain.

Before I finish, I want to just briefly mention one other aspect of drinking water. That is that a number of ecological studies have consistently shown an inverse correlation between the hardness of drinking water and the risk of coronary artery disease. That is, the harder the water, the lower the cardiovascular risk. Water hardness is largely determined by calcium and magnesium content. Of those two, magnesium seems to be the most heart-protective. It’s interesting to speculate about the relevant importance of this observation, since entire populations of people are affected by drinking water quality.

Even small increases in risks can have a significant public health implication, when they’re applied to large populations of people. We’ll hear that theme I think, as well, from our other presenters—who will be talking about exposures where entire populations are involved in each case, as well. I think I’ll stop there.

4. Second Speaker: Eliseo Guallar, MD, DrPH, Assistant Professor of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Associate Editor of the Annals of Internal Medicine and of the American Journal of Epidemiology

I want to thank Dr. Schettler for his first topic. He actually introduced many of the ideas that I wanted to talk about. We’re going to change gears now to mercury. But we’re going to continue talking about atherosclerosis and cardiovascular disease. I assume many people on the call will be familiar with some of the environmental issues related to mercury.

I wanted to start by talking about fish intake. Many of us working in cardiovascular disease for a long time have been studying, and some people actually are promoting fish intake as a source of theoretically cardio-protective amino 3 fatty acids—also called Omega 3 fatty acids or fish oils. This is a specific type of fat that you can get only in fish. We can produce this type of fat from other fats in our body—but not very efficiently. This type of fat from fish oils have several physiological effects that are thought to protect us from cardiovascular disease—including reducing the risks of fatal arrhythmias. Today, this is believed to be the major effect. But also, lowering triglyceride levels, lowering inflammation, and diminishing the activity of platelets, so it’s more difficult to have a blood clot.

Fish oils are thought to be so important that the American Heart Association currently recommends for the general public that everybody takes at least 2 servings of fish per week. That would be the minimum—with focusing on fatty fish—which are the fish richer in Omega 3 fatty acids. For patients who already have heart disease, the recommendation is even higher. They recommend 4 servings—or 1 gram of fish oils per day.

The link with mercury is that if we are pushing this recommendation of increasing fish intake for the general public and for specific subgroups of the population, we’re going in practice to be increasing the intake of methyl mercury and other contaminant in fish.

The reason I got involved in methyl mercury was because for several years, I was studying the effects and the association between these fish oils and cardiovascular disease. I participated in two large studies—one here in the US and another one in Europe. To my surprise, I could find no association between fish oil levels in different tissues and the risk of coronary heart disease. These were large, state-of-the-art epidemiological studies. I was very surprised with that, and also a little bit troubled.

At the time, I was completely focused on fish intake, and amino 3 fatty acids. Then I remember that one-day in late 1996, I read a paper published by Yuca Salon from a study called the Corpeus Ischemic Heart Disease Study, where they look at the association between mercury and cardiovascular disease. The problem they have in Finland is in the Corpio area, where people were taking a lot of fish with rather high mercury levels from the locally contaminated area. They found a positive association.

That’s the first time I remembered that I’d been all these years been thinking about fish oils and fish—but I didn’t realize that we were eating contaminants. Some of these contaminants can be very problematic. Fish is the primary source of methyl mercury. With mercury, to the opposite, as with arsenic—there are organic and inorganic forms. But the organic forms are thought to be more toxic, although all forms are probably toxic.

There are over-exposures to mercury in the general population. Amalgam is an important source of exposure to elemental mercury. Then there are also occupational exposures, and exposures to mercury in different rituals and other sources. But for this talk, I was going to focus on exposure to methyl mercury, derived from fish.

The mechanics of why mercury might impact cardiovascular disease are basically unknown, particularly, at the relatively low levels that we are talking about. We are not talking about the toxicological levels of exposures. We’re talking about low-level chronic exposure. Mercury can participate in the production of free radicals, and an increase of oxidative stress. That’s something that’s a common general mechanism for producing several chronic diseases—including cardiovascular disease, but it can interact with many proteins through the pathile group.

We don't really know what the specific mechanism is why mercury might be causing heart disease—even though in the few studies where this has been looked at, levels could be comparable to what the general population is exposed to. It seems that there is an association between mercury levels and oxidized LDL—which is one of the problems that are thought to initiate heart disease.

So this is a starting field. There is not a lot of evidence. I’m going to summarize basically the four main studies that have been done in this area. The first one, I already talked about a little. This is the Corpeus Ischemic Heart Disease Study, which is a study in Europe with relatively high mercury levels for the general population—showing the positive association. We repeated a study in 10 countries in Europe, and we also found a positive association between mercury and cardiovascular disease. We further found that mercury opposed the beneficial effects of the fish oils. This is probably one of the reasons why, in some cases, fish is not protective.

At the same time that our paper was published in the Journal of Medicine, there was a paper from the Harvard School of Public Health, done primarily in dentists, that showed no association between mercury and heart disease. Although, there was the resulting non-dentists who are the ones that are most likely to be exposed to methyl mercury. They were very similar to ours.

Then there was a smaller study in Sweden—unfortunately so small that it’s difficult to interpret. This is where we’re at, now. Here we are conducting a couple of studies that one of them will be ready in the summer. We don’t know the findings, yet—but this is an open question. The problem here and the problem with some of the fish advisories stories that have been put out, is that we run the risk of discouraging people from eating fish.

I think the way that we’ll have to evolve is first to make sure we understand all the beneficial effects and all the risks derived from the contaminants in fish. Second, to make sure that we give good advice and sound advice to the population, so that the general public can make the intelligent choice about fish intake.

5. Third Speaker: Murray Mittleman, MD, DrPH, Cardiologist, Associate Professor, Department of Epidemiology, Harvard School of Public Health and Associate Professor of Medicine, Harvard Medical School and co-author of the Air Pollution and Cardiovascular Disease Statement for Healthcare Professionals from the American Heart Association

It’s a great opportunity to present on this call. I was going to give you an overview of some of the data on air pollution and cardiovascular disease—largely based on the American Heart Association’s scientific statement that came out in 2004. It was meant to summarize the results of the research to date, and present challenges for future directions that need further data and elucidation.

The story about air pollution and cardiovascular disease really goes way back. Starting in 1930, with an air pollution episode with an inversion in the Muse Valley in Belgium, there was an association with a marked increase in total mortality. The next major episode was in 1952, in London. Actually, in that London Fog incident, there was a great increase in all-cause mortality in the days following the fog. Interestingly, going back and looking at the death certificates, it turns out that the majority of deaths—or a very large proportion of them—were due to cardiovascular causes. So, going back as far as the 1950s, there was evidence already that there was an association between extreme episodes of air pollution and transient increases in risk of cardiovascular disease.

Over the years—particularly in the last 20 years or so—there’s been increasing interest in this area, and increasing evidence—with really hundreds of publications, at this point, of epidemiologic studies linking air pollution to different health effects. Many publications look at the associations with heart disease. Particularly over the past decade, we have accumulated quite a bit of evidence.

I want to talk about the evidence on two different time scales. There are studies that involve the long-term health effects, and there are studies that look at short-term health effects. The long-term health effect studies are studies that look at what the association is between living in a region with higher levels of pollution over many years—and what that does to the rate of incident cardiovascular disease, or cardiovascular mortality. And then there are short-term studies that look at the effects of what happens with transient changes in air quality.

So does having a transient spike in the level of fine particulate air pollution, for example, with high levels today, influence your risk of having a heart attack or a stroke or an arrhythmia over the next hours to days? That’s really a separate question—because the mechanisms presumably are different.

In terms of the long-term studies, there are a couple of very important studies, going back. The first is probably the Harvard Six-City Study, led by a colleague of mine, Doug Dockery, here at the Harvard School of Public Health—where he studied over 8,000 adults for over 15 years, on average. He compared the mortality rates in individuals living in cities that either had higher or lower degrees of air pollution, and he found a considerable increase in the rate of all-cause mortality. But importantly, of mortality from cardiovascular causes, as well, living in regions with higher levels of air pollution.

Importantly, they did have very detailed data on individual level variables. They could statistically control for differences in tobacco smoking, obesity, educational attainment, occupational exposures, hypertension and so on. After adjusting statistically for these things, the effects were very consistent, and it didn’t seem to be accounting for the associations between high levels of air pollution and higher risks of heart disease.

More recently, the American Cancer Society Study with over half a million individuals reported results, actually twice now, there was a reanalysis. This was then looking at individuals across the country, with people from all 50 states—showing very consistent increases in the risk of all-cause mortality—but also deaths from cardiovascular causes, in particular, with chronic exposure.

Those are two studies that really are probably the most-important studies for global effects on a citywide basis. There’s good data showing within-city variation, living in areas that are where you’re exposed to higher levels of traffic sources of air pollution. They seem to be associated with the higher chronic risk. From a couple of studies, now—showing that living in close-proximity to roadways—or some of the more-recent studies, looking at the relationship between modeled levels of air pollution, based on wind patterns and geography—in addition to just looking at proximity to roadways as associated with a higher risk of mortality—whether there’s still some residual compounding from other social factors remains to be worked out in future studies.

There’s very good evidence from the epidemiology. There are annals models that also support the notion that chronic exposure can accelerate atherosclerosis. The culprits that have been looked at in terms of the pollutants—most strong evidence is for fine particles that are quite small less than 2.5 microns in diameter. That’s really a very small particle—smaller than a red blood cell, to put it into perspective.

In terms of short-term studies, there are really many studies that have looked at this relationship. The two largest studies were the NMAP study, which was a collaborative effort led by John Consammit at Johns Hopkins University, where they looked at outcomes in 50 million people residing in the 20 largest cities in the United States. It was able to show that transient changes—transient increases in fine particulate air pollution was associated with increases in mortality of an about less than 1 percent per 10 mcg per cub meter—which is a reasonably large increment. But again, when this effect is applied to very large populations of millions of people, this can account for a large number of excess deaths.

A similar study in Europe, in multiple cities, confirmed the same. That study really found virtually identical results. Those studies are looking at deaths from all causes, and then of cardiovascular causes from death certificates. That’s one level of evidence.

Another level of evidence is looking at more-specific outcomes that are non-fatal. At this point, there are several studies that show associations between air-pollution levels in the short-term—say, within hours or days—an increased risk of non-fatal heart attacks. That was a study that we did here in Boston, showing association within a period of as short as two hours following a spike in particulate air pollution levels. The risk of heart attack went up about 20 percent or so, over a two-day period, also, a consistent increase. Those findings have also been confirmed in a study in Rome. However, it’s important to point out that not all studies are positive.

A recent publication from the University of Washington, looking at non-fatal and fatal heart attacks in the Seattle area, did not find any association at all. Whether that’s a difference in the population or a difference in the constituent-specifics of the air pollution in the different regions of the country, really is a very hot area of research that requires further evaluation.

Important areas of research now are, “Are there populations that are of particularly high risk?” We are interested, particularly, in the elderly. Patients with pre-existing heart disease and patients with diabetes are the groups that are most likely to be affected.

In terms of other outcomes that show evidence of association—they include not just cardiovascular disease in general, but exacerbations of heart failure. So among patients with pre-existing heart failure, or admission to hospitals among Medicare beneficiaries, is increased within a day or two of a spike in air pollution levels, across many cities in the United States. Incidence of arrhythmias in patients who are vulnerable, who have implanted defibrillators. There are several publications now that show an association with life-threatening arrhythmias—although again, not all studies are positive.

Again, a study from the Northwest, out of Vancouver, failed to show an association between air quality and arrhythmia. That questions whether there’s something about the difference in the quality of the particles. Also, pretty strong evidence at this point for an association with stroke, particularly for ischemic stroke, where the mechanisms are likely similar, in terms of having both an atherosclerotic component and a clot formation component. So the evidence there is also pretty strong for acute effects of air quality on stroke onset.

In terms of mechanism, there’s really a lot of active research being done now—a lot of it at USC, and a lot of it at the University of North Carolina—looking at different mechanisms. Some of the hypothesized pathways where there are varying degrees of evidence involve both direct irritation of receptors in the lung, when you inhale these fine particles. They get deposited deep in the lungs, triggering changes in nerve inputs from the noxious stimuli, which changes the autonomic input into the heart, and alter conduction. They may lead to arrhythmias through that mechanism.

In addition, there is very strong evidence now that inhaling these particles can trigger pulmonary inflammation—acutely. This may trigger a systemic response. There’s good epidemiologic evidence that on the days following high pollution levels, the levels of markers of inflammation, including C-reactive protein and interleukin-6—which are markers that are associated with adverse cardiovascular events—do go up within days of exposure.

These together may contribute to making plaques in the coronary arteries more vulnerable to disruption, and also make the blood more coagulable. There are common increases in coagulation proteins—including fibrointergin that have been reported, as well as increased platelet activation. So there are mechanisms, both in terms of the neural inputs, the changes in the vasculature itself—in terms of increased constriction to blood vessels—and then finally, if a plaque is damaged, there appears to be increased inflammation and coagulation that can lead to these outcomes.

In terms of where we’re going next—there’s really intensive investigation, both in terms of long-term and short-term effects. There’s a lot of interest in confirming the findings—trying to understand the diversity of the findings. Why, for example, not all studies find perfectly concordant results. So the bulk of the studies are quite consistent—either as important research, looking at specific constituents in the air pollution, to looking at metals and organics that are in the mixture—to identify whether there are specific noxious components. And of course, looking at source-proportion. To try to understand whether, for example, diesel exhaust has a differential effect compared to—let’s say—long-range transported pollution from power plants.

Trying to differentiate the different health effects from different sources is another important area that will help to guide regulation in the future. Hopefully, we’ll have better data on what exactly the toxic components are, and where they’re coming from.

6. Question/Answer/Comments/Discussion

Michael Lerner: Thank you, Dr. Middleman—very much, and also to Dr. Guallar and Dr. Schettler. I’d like to ask Dr. Dean Ornish to make the first comment or offer the first question. Dr. Ornish?

Dean Ornish, MD, Founder and President, Preventive Medicine Research Institute: Thank you. This is really fascinating, Michael. The question is about fish versus fish oil. Since it’s almost impossible to find fish that are free of mercury and PCBs and dioxin and other pollutants—I think it’s wiser to recommend fish oil than fish. As you know, there are several brands of fish oil that have removed the contaminants, which has the added benefit of giving you just the right amount, without the extra fat. As you know, the fish that are the highest in the Omega 3s—the salmon, mackerel and halibut and so on—also tend to be the highest in fat, in general. So people are consuming a lot of calories and fat that they don’t need. Whereas, it’s my understanding that for people like Alexander Leiss and others, 3 grams a day of fish oil provide you about 1 gram of DHA and EPA—which is really all you need. More than that just gives you a lot of extra fat, without extra benefit. I’d just be interested in your thoughts on that.

Eliseo Guallar: Thank you for that question. This is a key area. Now, let me approach it from the perspective of cardiovascular disease epidemiology. The first thing is—I think we should be very reluctant to recommend compounds to the general population, unless we have a test. “Tests,” meaning randomized clinical trials that really test them out. We have a long history of very many nutritional components that were supposed to be good—were supposed to be very safe—but when they were tested, they were either big disasters or unique small disasters. We have the beta-carotene story, the Vitamin E story, and even hormonal replacement therapy. The studies—large studies—large, randomized controlled clinical trials in the general population—randomizing people to fish oils versus no fish oils—they haven’t been done. I think that will be an important issue.

What has been done have been studies of relatively large randomized control study of fish oils in patients who have myocardial infarction. This study was called GISSI-Prevenzione and it was done in Italy. Unfortunately, it was not double-blind, and I think people still would like to see the study replicate another in other areas. There are some studies in Europe that I think will tell us what is the impact of fish oil in people who already have heart disease.

Naturally, this GISSI-Prevenzione study was the basis for the American Heart Association to recommend in patients who already have coronary heart disease—that they should take at least 1 gram of fish oil—1 gram meaning eicosapentaenoic acid and docosahexaenoic acid per day—if people cannot tolerate this, to do it from supplements.

Now, I don’t think we understand completely what is the balance, or what are the tradeoffs between eating fish and eating supplements of fish oil, partly because fish has lots of contaminants, but it has not only fish oil. It’s a source of high-quality protein and it has other micronutrients. Compared to other foods, the percent of fat is nowhere I think compared to other foods that you might substitute, it might actually be healthier.

Getting back to the answer, in the general population, we don’t have the evidence that we should have to recommend fish oil supplements. They look good, but we still don’t have positive proof of efficacy. We don’t know that they’re completely safe.

Again, when we talk about “safety,” there is extensive experience with fish oil supplements. The argument is that you can take up to 3 grams per day of fish oils and still be considered safe. Again, those are in the smaller studies, where a small increase in mortality wouldn’t be picked up.

Philip R. Lee, MD, Professor Emeritus of Social Medicine, UCSF and the Institute for Health Policy Studies, Stanford University, Program in Human Biology: I want to ask two questions. One has to do with—Ted had a brief section of air pollution and public policy in his paper about what we should be doing—particularly in states like California—with a much higher percentage of the population in areas that are exceeding the current standards.

The second is, informing the public. This is an area I think the public is very poorly informed about. They know a lot about fat and coronary disease, but they don’t know a lot about air pollution and strokes and heart disease. I would like some comments on both of those questions.

Ted Schettler: I think that what Phil is pointing out—the question is, “How do you develop public policy with this information?” It’s not only heart disease, but it’s lung-development in young children, as well, that’s impaired by the current levels of ambient air pollution. It’s an outstanding question about the extent to which the population knows and cares about the outcomes that are being described.

Murray Middleman: I think from the point of view of being someone who’s working in the area of developing some of these data—we’re actively involved with some of the new research. I think we try to get the data out there. Groups like the American Heart Association and American Lung Association and so on are certainly advocacy groups that could be used. In addition to some of the more-traditional advocacy groups for these kinds of issues, the groups like the American Heart Association could be used.

I can tell you, I was very involved with the writing group, in getting this paper initiated. There’s very strong interest, in terms of getting out the information that exists. Given that, there is some controversy, still—in that not all studies show exactly the same results. It has to come out in a balanced manner. I think working through those organizations in addition to more-traditional environmental organizations would probably be very helpful.

Karen Florini, Senior Attorney, Environmental Defense: To what extent is it possible to indicate what fraction of heart disease might be attributable to environmental factors? If it’s not possible to answer that question at this point, what needs to be done before it can be?

Murray Middleman: It’s probably a relatively small percentage. But because heart disease is the Number 1 killer, a small percent of a very large number is a lot of excess deaths and excess events. In our paper in the American Heart Association, we had an estimate from the World Health Organization (WHO) estimating that there are 800,000 deaths occurring annually, and 7.9 million disability-adjusted life-years are lost, just to particulate matter exposure. Not just from heart disease, but overall. That’s from the Global Burden of Disease Study from the WHO. Within the US, there are estimates that if you could reduce the attainment of the current standards, you could reduce about 23,000 deaths annually in the US, and about 40,000 admissions to hospitals.

Sandy Buchanan, Executive Director, Ohio Citizen Action: We’re working with communities next to both refineries and steel mills. In both places, we’re interested in whether there’s been any more-specific investigation of the constituents in that air pollution on heart disease.

Murray Middleman: That’s actually an area that right now is being investigated. One of the conclusions of the heart association review was that this is exactly the kind of work that needs to be done, to look at the specific constituents to see if one can identify whether specific transition metals are particularly noxious.

So the work that’s been done to date has been more on a smaller scale—looking at more clinical studies and animal research. At this point, there has not been a really large-scale population-based study. But that’s something that’s being worked on now, and hopefully we’ll get better answers for, soon.

John O. Pastore, MD, FACC, President, Physicians for Social Responsibility: I’m a cardiologist in Boston. Not only are the public and perhaps public servants not too aware of this problem—but I think even our fellow cardiologists are not that aware of it.

My question basically is, “What do you think can be done about getting this into medical school curricula or medical grand rounds to a greater extent than it has been, so far?

Murray Middleman: I think right now, we’re at a point where evidence is accumulating, to a point where we likely will be able to get it more on the agenda. If you look at the publications to date of the papers that describe this—most of them have been more of the environmental journals, rather than in mainstream cardiology journals. I can tell you that our group and several other groups have a publication strategy of trying to—at this point—moving it more into the mainstream cardiovascular journals, and to bring awareness.

We’ve also had special sessions at the American Heart Association (AHA) National meeting two years in a row. I have been on the executive [board] for the epidemiology and prevention council of the heart association. We’ve had presentations for the last two years at that annual meeting. So part of it is just getting the people who are in the field to get it out there.

Historically, there have been very few cardiologists who have been doing this work. That’s part of the reason why it’s not getting into that field. But that’s been growing over the last couple of years. Hopefully, that will continue to grow. So that once the cardiology community and the general medical community are more aware of it, it will reach the next level, I hope.

Jeffrey Ritterman, MD, Cardiologist and Assistant Chief of Medicine, Kaiser Permanente, Richmond: First, I’d like to second what was just said. I told the Chief of Cardiology at Kaiser Northern California and his uniformed ignorance about this topic, as I see AHA statements. People are pretty informed about a lot of other areas, so I guess we have a lot of work to do. My question is, in the small particles, is that primarily coming from diesel? Or is that just your usual auto exhaust? And where would you focus your efforts?

Murray Middleman: It’s a controversial area, at this point. That’s a very hot area of research. Whether it’s just these ultra-fine particles—the stuff that comes right out of the tail pipes—diesel exhaust—or whether it’s other particles. Right now, it’s really an unresolved issue. There is some evidence that mobile sources—both diesel and conventional gasoline engines—are perhaps more toxic than other sources of particles. But that’s not really clear, at this point. The contribution from power plant emissions may also be important.

It’s something that’s being worked out. I can tell you our group is very focused in that area, right now, and we have a couple of ongoing studies—specifically, trying to differentiate that by using a combination of ambient city-wide monitors and local community monitors. To look at any discrepancy that we might find that could give us information. In addition to proposals that we have out there to look at specific constituents.

Michael Lerner: Let me pose a question. Where now we have the capacity to assess something like 400 different contaminants from human beings. Then we can do risk profiles of various kinds, and discover what subpopulations seem to be at higher risk for these contaminant exposures.

I wonder—I wanted to ask Dr. Guallar and Dr. Middleman whether first of all, biomonitoring as a tool is being used in these studies with heart disease, to assess whether people with higher levels of mercury, arsenic and other contaminants are having more incidents of heart disease. Secondly, whether the next step is being taken—of looking at the interaction between these body-burdens of contaminants and different, more-vulnerable sub-populations.

Dr. Guallar, would you take a first shot at that?

Eliseo Guallar: It’s a very important issue, because the answer is that we don't have those studies, in general. Part of it is as Dr. Middleman has discussed—the reluctance of some of this to be picked up by the cardiovascular community, with other contaminants—not being particles—has made it even worse. We’re in a position that some of these contaminants have been at least studied in large prospective studies for cancer outcomes and other outcomes. Some of the mechanistic—theoretical—mechanisms could also apply to cardiovascular disease. But I think it’s nobody’s plan. I think part is because all these contaminants are below the radar screen of people in the cardiovascular area.

We are trying to develop the area of cardiovascular diseases and heavy metals. We’ve heard about arsenic, mercury, lead, cadmium and probably other metals are likely to have important cardiovascular effects in our population. There are not a lot of people looking at them. With respect to other contaminants, I’m less familiar with the data, but I’m reasonably sure that they have not been looked at in major cardiovascular studies.

Murray Middleman: I would completely agree with those comments. I think that one of the problems with doing the kind of research that you’re proposing, which is clearly an important area, and something that ought to be pursued—it’s just that the actual risk or increment in risk associated with exposures is quite low on an individual level. It still adds up to a very large impact on the population basis. The studies that have been done that have detected these effects have been on very large populations. The expense of being able to look at these hard endpoints in vast populations is really daunting.

These kinds of studies are being done in smaller panel studies, for air pollution, anyway. Where smaller numbers of patients are brought in to be studied repeatedly, over some period. Some of the studies last for weeks, some last for periods of a year. They have some physiologic measures as surrogate endpoints—so changes in heart rate or blood pressure or changes in developing evidence of ischemia, walking on a treadmill, and so on.

There’s a quite large European Union study that is about to be completed that’s done this on over 1,000 patients across Europe. They had 1,000 patients with heart disease brought in repeatedly, and they’ve had extensive evaluation of biomarkers at each visit, as well as a battery of genetic markers to look for genetic markers in the inflammatory pathways, as markers of susceptibility to these intermediate-type outcomes.

Kathleen Burns, PhD, Sciencecorps.org: I wonder to what extent the occupational health community might be of some help in this. I’m thinking specifically of those docs that work with knowledge of environmental health issues, as well—like My Carbon in Michigan, where they have high endogenous levels of arsenic. They’ve looked at some of the mechanistic issues—the architecture within the vascular system—and so on. They’ve done some advocacy work on that. Can they work with the cardiology community to help get a better awareness of this?

Eliseo Guallar: I can comment specifically on the topics of arsenic and mercury. We still haven’t touched on the occupational studies of workers are exposed to either arsenic or mercury. Unfortunately, those studies are very inconclusive, because I think we have lots of methodological limitations. I think there’s a fascinating area for collaboration between the cardiology community and the occupational community to develop those studies. Certainly, in these two areas—studies with biomarkers of exposure—with vital assessment—if not of hard endpoints, at least of physiological measures that can provide information. I think a lot is to be done in that area.

Michael Lerner: Thank you, Dr. Guallar. We’re at the hour and I want to thank Dr. Schettler, Dr. Guallar and Dr. Middleman. The Collaborative on Health and the Environment really regards this as quite an historic point, where the American Heart Association has entered into the field of environmental cardiology. As Dr. Middleman indicated, having groups like the American Heart Association and the American Lung Association advocating in a very balanced way—for understanding these relationships—brings a whole new voice. It’s very important to the field of environmental health. So our gratitude to Dr. Middleman and Dr. Guallar for their pioneering work in this area and to Dr. Schettler for the excellent summary paper.

Eleni Sotos, MA, National Coordinator, Collaborative on Health and the Environment: Thank you to everyone for joining us today. I wanted to let you know that our next call, Over the Top: The Cumulative Impact of Environmental Health Stressors, has been set for Wednesday, May 18 at 9 PST/12EST. We hope you will be able to join us.