COMMENTARY

Cardiovascular Triggers Are in the Very Air We Breathe

Henry R. Black, MD; Robert D. Brook, MD

Disclosures

July 14, 2016

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Air Pollution Triggers Cardiovascular Events

Henry R. Black, MD: I'm Dr Henry Black, an adjunct professor of medicine at the Langone New York University School of Medicine. I'm here today with my friend and colleague, Dr Robert Brook. Bob?

Robert D. Brook, MD: My name is Robert Brook. I'm a professor of cardiovascular medicine at the University of Michigan, and I direct the Hypertension Center at the University of Michigan.

Dr Black: You have been instrumental in advocating the importance of air pollution in cardiovascular disease. Could you tell us how you got started with this issue and the main things that you have found over the years?

Dr Brook: I got started on this somewhat fortuitously while I was on the beach in the late 1990s with my brother, who just happens to be an atmospheric scientist. I thought that the haze I saw on the horizon on a summer day while looking over Lake Michigan was sea salt or sea haze. My brother promptly educated me that I was wrong and that it was, in fact, air pollution that I was seeing and not a natural phenomenon. This was when I first learned that I should be more knowledgeable about air pollution and its potential harmful health effects.

The thought at that time was that air pollution would cause lung problems, asthma, or chronic obstructive pulmonary disease and that it was less of a problem or perhaps not a problem at all to the heart. Over the following decade, emerging evidence from across the world has shown that the majority of the health effects of air pollution are, in fact, due to triggering cardiovascular events: heart attacks, strokes, heart failure, and sudden death. Because it affects so many hundreds of millions, if not billions, of people across the world, even a small increase in risk of perhaps 1%-10% for a cardiovascular event translates into a tremendous public health problem.

Air pollution, particularly fine particulate matter (PM), is the ninth leading cause of morbidity and mortality in the world and is growing across developing nations in Asia such as India and China, where the air pollution levels are accelerating and reaching extraordinary levels.[1] We have learned over the last decade that this is a serious public health problem. While principally a cardiovascular problem, that is not to say that it isn't important for the lungs and cancer as well.

What I was disappointed about and wish to improve upon is the lack of knowledge in physicians—cardiovascular physicians as well as hypertensionologists—that air pollution is really a cardiology issue. We published two American Heart Association scientific statements on the importance of air pollution as a cardiovascular risk factor and highlighted the importance to patients and healthcare providers of being aware of this major issue.[2,3]

Degrees of Air Pollution

Dr Black: You have classified degrees of air pollution. What standards do you use, and what are the measurements? How do we know when there is too much other than by what we can see?

Dr Brook: Excellent question. There are several different ways this is done. We typically speak in terms of fine PM. We say PM 2.5, which means particles that are less than 2.5 µm in diameter. They come from all sorts of fossil fuel combustion, mobile sources such as traffic, coal combustion, and the energy production industry in the modern world.

There are World Health Organization (WHO) standards as well as the National Ambient Air Quality Standards in the United States. PM 2.5 is generally measured in weight/m3, so we're talking about an average in the United States of about 10 µg/m3. To put that in perspective, PM levels in a smoky bar are about 500 µg/m3.

In the last 30 years in the United States, we've gone down from levels of 25-30 µg/m3 in the 1970s and 1980s to better controlled levels of an average of 10 µg/m3. Both the WHO and the US Environmental Protection Agency publish air quality indices on websites, national newspapers, and local media sources that bring together not just PM 2.5 but other criteria pollutants such as ozone and nitrogen dioxide. They provide an integrated scale of a person's exposure to air pollution levels in the United States. These are widely available for the day as well as forecasted. They tell you the worst air pollutant and the individual pollutant levels.

I'd like to highlight that air quality is overall a "success story" in North America. We've seen dramatic reductions due to air quality regulations during the last 40 years. We have seen it translated to an improvement in all-cause mortality. The reduction in air pollution has led to a 6- to 7-month increase in life expectancy in the United States,[4] but that's not to say that the problem is completely solved. Close to 20%-25% of American citizens are still exposed to levels above the WHO standards of 10 µg/m3, with many hot spots near roadways or in urban industrial locations. Unfortunately, low socioeconomic status populations are vulnerable and exposed to high levels.

Like many things, we have exported our problem to the developing world, where hundreds of millions or billions of people in Asia, particularly China and India, are exposed to high levels of pollution. Unfortunately, these are precisely the locations where cardiovascular disease and cardiometabolic diseases such as diabetes and hypertension are also burgeoning. There is a coepidemic and confluence of high air pollution levels, metabolic syndrome, hypertension, diabetes, and heart disease.

Although it's a problem in the United States, I would say that we've been heading in the right direction. Now is not the time to rest on past laurels. However, much of the world is exposed to extraordinarily higher levels than the United States is now. Much of our attention needs to be focused internationally.

How Does Air Pollution Trigger CV Events?

Dr Black: Bob, you've made a very compelling case for the problems with air pollution. Can you be specific as to the mechanisms for cardiovascular risk with air pollution and the exact effects?

Dr Brook: This is what we've been studying for the last 20 years. What are the pathways whereby the inhalation of fine PM triggers cardiovascular events? For example, second-hand smoke levels are probably around 500 µg/m3. Inhaling one cigarette delivers well over 5000-10,000 µg/m3. One cigarette is perhaps a whole month of air pollution in Beijing, China. Some of the questions from 20 years ago examined how very low levels of fine PM—1000th the dose of one cigarette—could possibly trigger cardiovascular events. How could it possibly cause heart attacks, strokes, and heart failure even at the low levels that we see in the United States now?

We and other scientists have done a host of toxicologic, basic science, animal exposure, and human exposure studies in randomized controlled fashion. Human panel studies show that there are generally three broad pathways. In the end, air pollutants can trigger vascular endothelial dysfunction, acute vasoconstriction, and enhanced platelet reactivity. This leads to augmented or heightened thrombosis potential and coagulation potential, with resultant arrhythmogenesis and arrhythmias and an imbalance in autonomic tone.

The question that has arisen from this research is: What are the mechanisms whereby inhalation of the particles into the lungs causes effects that are remote to the site where they were inhaled? A series of studies have shown that, broadly speaking, air pollutants can trigger inflammation in the lung. This nidus, or locale of inflammation, is not isolated and not just confined to the lungs. Much as in other scenarios such as obesity or rheumatologic diseases, this inflammation spills over to the systemic circulation and acutely or perhaps more subacutely and chronically leads to the generation of vascular and cardiovascular tissue inflammation and oxidative stress, which is known to play a fundamental role in the genesis of endothelial dysfunction, vasoconstriction, and atherogenesis.

Another pathway is the rapid autonomic imbalance that inhalation of these particles triggers. The lung can sense these particles and can promote a rapid reduction in vagal tone, an increase in sympathetic tone, and an increase in blood pressure, causing vasoconstriction and promoting arrhythmia.

Finally, many of the chemicals that are leached on the particles or the very small nanometer-sized particles themselves can likely be transmitted systemically throughout the whole body and have direct effects on the heart and blood vessels. We know that inhaling cigarette smoke is a convenient way to deliver nicotine into your body. There are thousands of organic chemicals and metals enriched on fine particles, which can generate oxidative stress throughout the cardiovascular system.

In conjunction, these three pathways can lead to a host of adverse physiologic responses that trigger acute effects. What we have found to be very interesting is that inhalation of particles over the long term can have a much more robust and large adverse effect. If we can cause a triggering of cardiovascular effects with perhaps a 1%-2% increase in heart attacks or strokes with a 10 µg/m3 increase in particles over 1-2 days, that same exposure of 10 µg/m3 over a year leads to a 10-fold increased risk for cardiovascular effects—a 10%-20% increased risk.

It raises the question: Do repeated exposures or chronic exposures promote chronic disease states that enhance susceptibility in the long run? The inhalation of particles over a year promotes the development of chronic hypertension and diabetes. As demonstrated in a very recent study[5] published in the Lancet from the Multi-Ethnic Study of Atherosclerosis and Air Pollution, [this exposure] promoted the genesis of atherosclerosis itself. Coronary calcification was actually potentiated and enhanced due to long-term air pollution exposure. It may be more than just triggering cardiovascular events in higher-risk patients. It may indeed be promoting the genesis of the metabolic syndrome and atherosclerosis in the population at large over a long period of time.

Air Pollution Is Only One of Many Factors

Dr Black: Do differences in air pollution explain why some parts of this country, such as the stroke belt, have surprisingly different levels of heart disease? We used to talk about the stroke belt and blame it on diet. Is it something else?

Dr Brook: Excellent question. Investigators have looked at the geographic relationship and geographic disparities of cardiometabolic disorders and to what extent air pollution might explain these phenomena. The stroke buckle in particular was looked at, for example, in the REGARDS cohort, and there was no evidence that it can be explained by higher pollution levels.[6] In fact, the air pollution levels are modestly lower there.

It's important to say that air pollution is only one of many factors. Of course, salt, diet, obesity, and exercise play a role in heart disease. As the metabolic syndrome, cardiovascular events, and hypertension have increased in the United States, air pollution has actually fallen. It's one important factor, not the sole factor, which works in conjunction with lifestyle and diet. Within major mega cities in the United States, Los Angeles being the classic one, you can see clear relationships between changes in air pollution levels and proximity to roadways and point sources of pollution with the increased risk for mortality in those who live in less advantaged urban settings. Some of it is due to air pollution, some of it is due to the stress and the noise, but higher air pollution levels do explain some of the gradients in cardiovascular risk that you can see at an urban level.

Dr Black: There are some societies where people wear masks when they go around. Should we start doing that?

Dr Brook: Absolutely not in the United States. It's probably not socially accepted as it is across much of the world. Again, I'll stress that although we have seen relationships between fine PM as low as 5 µg/m3 and cardiovascular events, you might have to go to Antarctica or to the Yukon territory to chronically get levels lower than that. I certainly don't propose that everyone moves to Antarctica or to northern Alaska. Maybe a tropical island such as Hawaii might be a good choice.

We do see low levels of air pollution causing cardiovascular effects, but this is a success story in general in the United States. Many of the problems that we see in China and the rest of Asia are because they're exposed to levels between 100 and 500 µg/m3. That's 10-50 times what we're exposed to here. It's a very natural question. Do those face masks, home air filters, or purification systems with HEPA filters reduce exposures and translate into improved health? There are some beginning studies to suggest that this is indeed the case.[7] You can reduce blood pressure and myocardial ischemia in patients with coronary disease in China by wearing face masks. The studies that have looked at this, though, looked at N95 respirators, which are much more effective masks than the simple surgical masks that you commonly see people wear in Asian cities. Those are made to protect other people from your respiratory droplets; they weren't made to protect you from the inhalation of particles. However, we find that they do provide some partial protection, and it needs to be studied to see what health benefits there may be from wearing those simple face masks. We've seen that air filters in Shanghai and highly polluted areas of India can reduce indoor 24-hour pollution exposures by up to half.[8] Perhaps this partial protection translates into benefits.

Inflammatory markers of systemic inflammation such as C-reactive protein and interleukin-6, platelet activation markers such as CD40 ligand, blood pressure, and ECG changes have been improved in some small studies. I believe that this is a very important issue for the future to see what interventions individuals can undertake. What are worthy meritorious lifestyle changes that people can make to reduce their overall air pollution exposure and protect themselves from the harmful levels that you'll find across Asia and developing countries?

Dr Black: Bob, I want to thank you very much for your excellent discussion and for bringing this issue to the fore. I think you've been making a great contribution, and I look forward to air pollution getting even lower. Thank you.

Dr Brook: Thank you very much for the opportunity to have this discussion today.

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