The Man Who Touched His Own Heart

by Rob Dunn

  Many studies have compared stents and coronary bypass and found them to be similarly effective in situations where a coronary artery is blocked or nearly so (that’s not the case if a patient actually experiences a heart attack and his condition becomes unstable or if he suffers from three or more clogged coronary arteries3 or from diabetes). Functionally, this means that given the choice between those two options, doctors tend to choose stents, since the procedure can be done at nearly any hospital, whereas bypasses require heart surgeons (who are ever more rare, thanks to the rise of stents). Also, as one cardiologist bluntly put it, “Stents don’t require you to have your sternum sawn in half.” As a result, stents have become progressively more common while bypass surgeries have become progressively less common, the same general trend that has occurred with cardiologists relative to heart surgeons.

  But just comparing stents and bypass assumes that one or the other of these two procedures is the best solution. A 2012 review in the Archives of Internal Medicine compared patient outcomes for stents (which, as noted above, tend to be similar in effectiveness to bypasses) with patient outcomes for noninvasive medical treatment (that is, drugs and lifestyle interventions). The review combined the results of all studies in which treatments (stent versus non-stent) had been randomized.4 Collectively, these studies included 7,229 patients, about half of whom were given stents and medicine and half of whom were given medicine alone. It is the biggest such analysis to date. On average, the patients in the studies were followed for a little over four years. Given the cost and sophistication of stents, one would expect those individuals who received them to be less likely to require another heart intervention, less likely to have a heart attack, and less likely to die. Statins and other medicines involve taking pills; stents involve having a device run up your blood vessels and into your coronary artery, where it will remain. Surely, stents are much better than the use of drugs alone. It scarcely seems necessary to make the comparison. Stents open up the artery and hold it open; that this is progress can hardly be doubted.

  This chart shows the rise in the use of coronary bypass surgery, stents and other related procedures, and cholesterol-lowering drugs (statins) through time. Data are for the United Kingdom, but similar trajectories exist for the United States and elsewhere in the affluent world. Also shown is the declining number of deaths due to heart disease through time due to changes in the prescription of drugs, the use of new procedures, and, to a lesser extent, diet.

  It should be. With stable coronary atherosclerosis, stents are not, on average, any better at reducing the risk of heart attacks or death than treatments with drugs and behavioral changes are. Overall, the results for drugs and stents were the same. Where there were differences, the medical therapy alone (drugs and diet) fared better. Patients who were prescribed medical therapy alone were no more likely to require subsequent intervention or surgery than stent patients. They were no more likely to die. They were no more likely to throw a clot. The only difference appears to be in terms of symptoms. With medical therapy alone, patients were less likely to have resolution of their symptoms, including their chest pain. In other words, the Canadians very clearly have it right (depending on how much we weight the treatment of symptoms). Despite the stents’ long history. Despite the brilliant men who pioneered them. Despite the billions of dollars made placing them. Stents show no evidence of being any better as a treatment for stable angina than just taking the right drugs and living a lifestyle along the lines of the one proposed by Ancel Keys, including exercise.

  The results of two studies performed in the 1980s and 1990s conflict with this new finding, but both do so superficially and in expected ways. In the 1980s and 1990s, the comparison that could be made in studies was between angioplasty and treatment with aspirin and ACE inhibitors (but no statins). In this comparison, angioplasty is better. But when stents are compared to treatment that includes Endo’s statins, stents do not perform better. At a cost of more than thirty thousand dollars each, they perform extravagantly the same. Death rates were about 9 percent in both groups, and among those who did not die, rates of nonfatal heart attacks were slightly higher for those who had stents than for those who just took medicine.

  The choice of solutions in different regions seems to have as much to do with money and local culture as with success. In the United States, most hospitals have gone to fee-for-service systems. Hospitals and doctors are paid more if they perform procedures, which is especially (economically) beneficial if those procedures are relatively easy. The stent falls precisely into this category. Many, many doctors can now place stents. They do so easily, at least when compared to the challenges of a coronary bypass. These stents have made hospitals huge money, but the stents collectively cost patients and health-insurance companies billions of dollars a year in the United States alone, most of which goes to the doctors, the hospitals, and the companies that produce stents. In some hospitals, half of all revenue comes from inserting stents. As one doctor put it in an interview with the New York Times, “When you put in a stent, everyone is happy—the hospital is making more money, the doctor is making more money.”

  But how could this be? Stents do seem to open up clogged arteries. Bypass surgeries create new arteries. Both approaches match up with our intuition about how to clear a pipe. Here there exists an important subtlety revealed only recently, a subtlety in the biology of atherosclerosis, a subtlety that reminds us of the many ways in which arteries are far more than simple pipes. Well into the 1980s, physicians and researchers assumed that the clogging of arteries was progressive. Cholesterol and immune cells accumulated in artery walls until the ever-thickening walls simply touched. This is in line with da Vinci’s speculation but also with the thinking of nearly everyone working on the heart over the past hundred years. Physicians and researchers assumed atherosclerosis, like the accumulation of sediment in the bottom of a river, was slow and progressive. But in the 1990s, it began to become clear that this model was, just maybe, not quite right.

  In the 1990s a series of studies showed that arteries clog not because of progressive narrowing alone, but because of a combination of narrowing, atherosclerosis due to plaques, and ruptures of those plaques. When plaques rupture—break open—they spill their contents into the arteries. Those contents—a messy mix of cholesterol, immune cells, and triglycerides—then trigger blood to clot. It is this clotting that clogs the arteries; it is the clotting that deals the final blow. While both stents and bypass surgeries open the coronary arteries, they do not clear the plaques out of the rest of the arteries, and so when plaques in arteries anywhere in the body blow, the mess that results can travel to the coronaries and clog them. What is more, while bypasses and stents often target big plaques, recent work suggests that it is actually intermediate plaques that are most likely to rupture.

  In light of this model of artery clogging, the thrombosis model, the limited and somewhat idiosyncratic success of bypasses and stents make sense. The arteries are not just pipes that clog; they are living tubes subject to phenomena that are complex and poorly understood. This model also suggests some of the reasons that aspirin and beta blockers (and even statins) work. Statins work because, just as Endo thought, they reduce cholesterol levels in the blood, but more specifically, they lead to the removal, by the body, of cholesterol in existing plaques. Aspirin works by decreasing blood clotting, which makes clogs due to thrombosis less likely (in other words, you take aspirin if you have clogged arteries because it will help prevent a heart attack on the one day a plaque does break open). Finally, beta blockers help reduce blood pressure, which reduces the force of blood on plaques, which reduces the chances they will burst. All of these drugs are different from stents in that they reduce atherosclerosis, the threat of thrombosis, or both, and in doing so, they systematically decrease the risk of the arteries clogging so severely a heart attack occurs. Remarkably, after a century of racing into the heart, a century of trying to mend or even replace that vital pump, we are only
just beginning to understand which elements of what has been achieved have actually been successful.

  Other successes have come in terms of prevention of heart disease and treatment of its consequences, though the relative significance of different preventive measures is hard to judge. Most research findings are similar to the Archives of Internal Medicine study results in that they highlight the importance of drugs that reduce blood pressure (such as beta blockers), drugs that reduce blood coagulation (such as aspirin), and drugs that reduce levels of cholesterol and inflammation (statins). There’s also another important factor in heart-disease prevention: a reduction in smoking.

  There is no Ancel Keys in the story of smoking and heart disease, no singular advocate or discoverer. Instead, in the 1970s, it began to be noticed that smokers were at greater risk of heart disease. There was never any controversy as to the existence of such a link. The debate revolved around why it existed. The reasons appear to be multiple. Smoking increases the risk of heart disease by constricting arteries and increasing the incidence of clot formation in blood. It also increases inflammation by introducing small particles into the lungs to which the immune system responds as though they were living, foreign, and dangerous. It does all of this in both those who smoke and those who experience smoke secondhand.

  Smoking is interesting in terms of its effects on our bodies. But it is also interesting in the context of how a decrease in smoking has been engineered. Public-service announcements proclaimed the ills of smoking, just as Keys proclaimed the ills of fat, but such proclamations did not have much influence. What did have an effect were laws, regulations, and taxes. As a result of these tools, tools of policy, it has become more difficult to smoke, more costly, and more unpleasant. In restaurants and other public places in most states, smokers must now cluster on back steps, blowing smoke in one another’s unhappy faces as rain falls on them and the cold or hot wind blows. What was once a glamorous activity is now associated with social, legal, and financial marginalization. As a result, the incidence of heart disease (and lung cancer) has declined in lockstep with reductions in the number of people who smoke and the number of cigarettes smoked by those who do.

  Changes in policies surrounding smoking improved the health of not only smokers but also those who didn’t smoke. A recent report by the Institute of Medicine found that in countries as diverse as Italy, Canada, and the United States, reductions in smoking led to decreases in heart-disease risk. The extent of the reduction was never less than 6 percent and was as high as 45 percent in some regions. Even the most modest of these impacts, 6 percent, is more of a decrease than is seen when people on modern Western diets switch to Mediterranean diets.

  The success of taxes and laws in discouraging smoking offers many lessons. One is that if you want to reduce negative elements in people’s lifestyles, you must do more than just urge people to change. It is not personal choice that alters the healthfulness of behavior in the biggest ways; it is the landscapes society engineers, be they legal, political, or physical. One of the best examples of how powerful and immediate such changes can be comes from an effect on the heart that, like secondhand smoke, is difficult for any individual to control on his or her own: urban pollution.

  Like smoking, air pollution causes increases in the rates of heart disease and heart attacks. It is the smallest particles of pollutants5 (2.5 micrometers in diameter and less) that cause health problems. They affect our lungs, these particles, but they have bigger impacts on our hearts. Like cigarette smoke, they cause arteries to constrict (and hence blood pressure to rise). Like cigarette smoke, they cause clots to form. And like cigarette smoke, these particles trigger inflammation.

  Recent studies suggest that reducing the concentration of these particles could reduce death due to heart attacks by about 12 percent. Before the Olympics were held in Beijing, Chinese officials cleaned the air over a period of months leading up to the event by restricting the use of cars in the city and decreasing the activity of power plants outside the city. When they did, the rates of heart-disease-associated deaths fell. After the Olympics, the power plants started back up and the cars once more took to the roads. Deaths due to heart attacks increased again. Apart from quitting smoking, getting rid of pollution can contribute more to reducing the risks of heart disease than nearly all of the other preventive measures that have been discussed so far. At least in theory, pollution, like smoking, can be controlled, and by its very nature, it is a public phenomenon. Short of moving somewhere with clean air or staying inside, no individual can alter his or her own fate with regard to pollution, but laws can affect pollution, as can the decisions that individual cities make. So can urban trees and, it turns out, beetles.

  In 2002, the first emerald ash borer (Agrilus planipennis), a small, green, jewel-like beetle, was found in Detroit, Michigan. Soon there were two, then two thousand, then hundreds of trillions. Yes, hundreds of trillions. The borers are native to Asia and eastern Russia and are intruders in Michigan; they spread in shipped wood. In Asia, they are innocuous, but in North America, when they find ash trees, they kill them, slowly but inevitably. Just why these beetles are so much more deadly in North America than in their native lands is unclear, but it relates in part to the immune response of the trees they attack. The North American trees overreact to the beetles; it is this overreaction that leads to the trees’ death.

  Once established in Michigan, the beetles spread unchecked across the state and into adjacent states, killing essentially every ash tree in their path. Ash trees are often planted as street trees, and so the effects were greatest in neighborhoods. Suburbs that had once been shady warmed with sun. More than a hundred million trees have died so far (roughly one for every adult in the United States), and as the beetle spreads, even more seem doomed.

  The death of so many trees is tragic. It affects the birds, the bees, and all the other species that depend on trees. But when Dr. Geoffrey Donovan, a scientist who works for the United States Forest Service in Portland, Oregon, thought about these trees, he worried about humans. Donovan had spent most of his career measuring the benefits and costs of trees. Trees affect property values. They can help reduce crime and increase the time adults and children spend outdoors. Trees also, it’s been suggested, benefit human well-being and health, particularly cardiovascular health. In one study in Tokyo, for example, seniors who lived nearer to green space tended to live longer.6 This could be due to the beneficial effects of trees on pollutants (trees pull many pollutants out of the air), though it could also be due to other benefits of green spaces.7

  A study in which people’s exposure to trees was altered while everything else in their lives remained the same would be compelling. Donovan realized that the emerald ash borer’s invasion represented just such an alteration, an accidental experiment replicated in tree after tree across the Midwest. Donovan speculated that when the ash borer killed trees, it might also be killing humans by increasing the pollution around them in cities (which increased risk of heart disease and other cardiovascular problems). In theory, this was conceivable, but theory predicts many features of the world that never come to be. Yet Donovan had that great arbiter of theory: an empirical test.

  Donovan and his colleagues compared the change in the number of ash trees in a region to the changes in health in those same regions. What theory predicted was that in those regions where more trees died, health metrics, particularly those associated with cardiovascular disease, should worsen. Making this comparison took time. The data sets on human health and tree deaths had to be combined. Analyses had to be worked out. Treacherous analytical bridges needed to be crossed. But eventually, Donovan had the results, and they were even more striking than the theory had predicted. Where ash trees died, cardiovascular diseases and deaths due to cardiovascular diseases became more common. Between 2002 and 2007, Donovan and his colleagues estimated, fifteen thousand more people appear to have died of heart disease in Michigan and eighteen other Midwestern states due to the de
ath of the trees than would have died otherwise. The ash borer has proved more dangerous in the Rust Belt than any other animal (aside from humans).

  The deaths associated with tree loss might not be exclusively associated with tree-mediated air pollution. Trees provide other health benefits. They reduce stress. They reduce temperatures (treed parts of cities can be as much as six degrees centigrade cooler than areas covered in cement). But pollution seems to be a big part of the story. The effects of the trees are greatest in more affluent areas, where trees tend to be planted in higher density, suggesting the possibility that losing trees is bad but losing more trees might be worse. Meanwhile, the beetle continues to spread. It seems likely to spread everywhere there are ash trees, from sea to shining sea. By some estimates, this tiny beetle could kill as many as 7.5 billion trees, one for each human on Earth, before it is done. With those trees gone, if Donovan and his colleagues are right (and if the effect of the loss of a tree is the same regardless of where it occurs), a tiny beetle might have killed as many as a million people.

  If there is good news in this story, and I think there is, it is that if the death of trees can take lives, then planting trees should save them. While it has proved hard to help people change their diets and behaviors in ways that affect the health of their cardiovascular systems, it is easy to plant trees. It is easy to imagine new cities, cities in which policies make us less likely to smoke and in which trees can be gardened for our health.