The George W Bush stent case: An incredible teaching opportunity on the basics of heart disease

The wrist artery hardly had time to seal. (Surely it was a radial.) The controversy came that fast.

The drumbeat of naysayers seemed to start only minutes after a prideful press release announced that George W Bush had undergone successful cardiac stent placement. The ever-quotable cardiologist from Cleveland Clinic, Dr. Steven Nissen, said, “This is really American medicine at its worst.” Dr. David L Brown, from Stony Brook University, and author of an important 2012 study on stents, added that GWB was “now the poster child for the inappropriate use of stenting.”

How could this be? It must be a good thing to uncover and treat heart problems before damage occurs. What do you mean he shouldn’t have had a blockage ‘fixed’ with a stent? Blockages are bad; let’s get them cleaned up. A clear artery is better than an obstructed one, right?

These common sense notions and the intense debate surrounding GWB’s stent offer us an incredible teaching moment for heart disease. It’s hard to believe our number one killer could be this misunderstood. But it is. Both doctors and patients struggle with the basics of atherosclerosis (hardening of the arteries).

This is big. Hidden in the nuances of the GWB case are important messages about the process of atherosclerosis and the significance of the vulnerable plaque. I believe advancing the knowledge of basic atherosclerosis would go far in correcting much of the over-treatment in cardiology today. The false expectations of screening stress tests and the surprise over the lack of benefit of stenting non-symptomatic disease illustrates the wide swath of misinformation out there.

My aim is to use this controversy to spread the facts and fundamentals about atherosclerosis and heart disease.

Consider this question as you read: If you had the choice between two types of blockages in one of the three main coronary arteries (the arteries that supply the heart), which would you choose: Choice A is a thick smooth 80% blockage. Choice B is a thin-walled 10% blockage.

The GWB story:

A former president of the United States gets careful medical attention. In the course of this quite careful care, a significant coronary blockage was discovered. Like many patients with heart disease, Mr. Bush had no symptoms. He did not report chest pain, shortness of breath or dizziness. He is known to be an avid cyclist, a mountain biker even. I don’t know the former president, but I know mountain bikers. He likely demanded a lot from his heart at times. GWB is also special in that it’s hard to quantify the inflammation of 8 years in the White House. (You writers know how much criticism inflames; imagine half the free world thinking badly of you.)

The controversy in this case centers on two issues: First, why did a non-symptomatic patient get an exercise study in the first place? Second, why was a stent used to treat a blockage that was not causing symptoms?

Lack of benefit for stents in stable coronary artery disease:

Let’s begin with the second issue and work backwards. To understand the stent debate, we need to start with the aptly named COURAGE trial, published in 2007 in the New England Journal of Medicine. Researchers screened many thousands of patients to come up with about 2300 study subjects with significant coronary artery disease–similar to the former president’s. COURAGE studied two treatment strategies: about 1100 patients were randomized to optimal medical therapy and another 1100 had optimal medical therapy plus a stent placed in any blockage greater than 70%. Researchers made sure both groups had intense medical therapy, including regularly scheduled nurse-managed visits, free medicines, and dietary and exercise counseling. They then followed patients for five years and compared hard outcomes. COURAGE got its acronym because it was felt courageous to leave patients with major blockages on medicine alone. Prevailing wisdom held that major blockages needed to be stented. (But you know how prevailing wisdom often turns out.)

COURAGE investigators showed that adding a stent to optimal medical therapy and lifestyle changes made no difference in the risk of death, heart attack or stroke. Criticism of COURAGE was robust. The trial enrolled mostly white male patients and bare metal (not drug-eluting) stents were used. Some said the intensity of medical therapy was unrealistic in the real world. (A highly relevant criticism in this era of lean healthcare delivery.) Applicability of COURAGE was also called into question as the investigators had to screen many thousands of patients to get down to 2300 subjects.

These findings, however, turned out to be no fluke. In 2012, a meta-analysis of 8 similar stent trials (JAMA –IM), including 7229 patients, confirmed the lack of benefit for stents in patients with stable coronary artery disease.

It was settled then: stents should be used only in symptomatic patients, like those having heart attacks, chest pain, arrhythmia, or in those with weak hearts and congestive heart failure. Using stents preemptively did not work to prevent heart attacks, strokes or death. For the record, when angioplasty (the precursor of stents) was used in asymptomatic patients, it did not prevent heart attack, stroke or death either.

The explanation: Consider basic atherosclerosis.

Coronary artery disease stems from diffuse disease of the blood vessel wall. (We call the inner lining of the blood vessel the endothelium.) Wrong thinking holds that blood vessels are inert pipes that carry blood to organs. So, if a blockage exists, squish it open and voila, it’s fixed. This is total nonsense. The blood vessel wall, the blood itself, and their interaction are wildly active in a biologic sense. (I hate the word dynamic, so let’s just say the endothelial-blood interface is far from static.) Sticky platelets, irritable endothelium, the two together–this is heart disease.

Think of the things that can happen in a blood vessel: One possibility is that over time a slow-growing thick-walled plaque accumulates cholesterol and fat. The growth may enlarge enough to obstruct blood flow to the heart (or any organ). These ‘stable’ blockages can cause angina—a short supply of nutrients at times of high demand. Though impressive to look at, because of the degree of obstruction, these plaques are less of a problem. We say they are less vulnerable to rupture. What’s more, not only are these thick stable plaques unlikely to rupture, but the downstream heart muscle gets accustomed to periods of low nutrients–ischemia. We say that part of the heart is pre-conditioned for ischemia. (I’ll come back to that.)

Another (more worrisome) thing that happens in blood vessels can occur in the earlier phases of heart disease. It’s these younger, less developed, thinner-walled and nonobstructive plaques that cause heart attacks, strokes and sudden death. These are the vulnerable plaques. Because vulnerable plaques don’t obstruct blood flow and rarely have calcium in them, they are neither symptomatic nor detectable by stress testing, coronary CT or heart catheterization. Innocuously termed “lumen irregularities,” these areas of disease are where the danger lies. Here’s why: the thin-walled plaque is more likely to fissure. A tiny crack exposes the inside of the plaque to components of the blood. What happens to your skin when you cut it? It bleeds, and then a clot forms. That’s okay on your arm, but clot formation in the inside of a blood vessel leads to abrupt occlusion of the vessel—a heart attack or stroke. And sudden death due to arrhythmia can occur in this scenario because the supplied heart muscle is not used to low nutrient levels. Non-preconditioned heart muscle is electrically irritable. Plaque rupture is why people can die suddenly the day after a normal stress test.

And there’s more. Non-obstructive, possibly vulnerable, plaques occur throughout the three major coronary arteries. Yes, there may be one bad 80% blockage, an eyesore that captures the attention of the cardiologist, but when there is one bad blockage, there are often many other much more vulnerable plaques. So the problem with the major blockage is not just the restriction of downstream blood flow, but rather, it’s a marker for diffuse atherosclerosis. That’s one reason why stents don’t prevent heart attacks or death. The stent treats the blockage least likely to cause the calamity.

But that’s not the only problem with stents. Another issue is that stents create their own disease. The metal cage inside a blood vessel can act as a source of clots. This means patients with stents must take drugs that block platelet function. These “blood thinners” increase the risk of bleeding. The duration of anti-platelet treatment varies depending on patient and stent characteristics, but is often long-term. Stopping an anti-platelet drug shortly after a stent, say in the event of trauma or surgery, greatly increases the risk of abrupt stent closure and heart attack. So stents aren’t free; they come with significant long-term tradeoffs.

The role of Inflammation:

Coronary artery disease equals atherosclerosis. It is a diffuse process involving inflammation in the blood vessel wall. The things that cause atherosclerosis are well-known, and work through chronic inflammation. Smoking is especially terrible. It causes long-term plaque accumulation, increases in platelet stickiness and irritation of the blood vessel wall. Smoking cessation results in near immediate decreases in vulnerable plaque rupture. It’s why you see so many fewer heart attacks with smoking bans; removing exposure from smoke has an immediately soothing effect on blood vessels. High blood pressure exerts its effects on the blood vessel via physics. Imagine 100,000 daily pulses of blood through a soft flexible blood vessel versus a stiff non-complaint hypertensive one. Stiff pipes are more apt to crack. Diabetes wreaks havoc in many ways. Insulin is a real baddie for blood vessels. As a growth factor, insulin causes deposition of fat in plaques. As an inflammation mediator, insulin contributes to the irritability of plaques. You don’t want high insulin levels; this is why a low-calorie diet devoid of simple sugars is so effective. Ask the healthy 90-year-old farmer from Indiana, how much food from packages he eats. Stress takes a toll over time as well. We know chronic angst, unhappiness and anger all associate with heart disease. The common denominator here is also inflammation. When you are inflamed emotionally, so are your platelets and endothelium. Genetics plays a strong role too. We inherit eye color, personality, intelligence, aerobic prowess and so on. We also inherit susceptibility to arterial disease.

I hope you can see why treating and preventing heart disease is not just about squishing low-vulnerability plaques. You can understand why the COURAGE trial showed that adding stents to optimal medical therapy did not lower the risk of heart attack or death. And, if the plaques most likely to kill are not obstructive, you can also understand the limits of stress testing.

Effective treatment of heart disease:

Although we are not close to knowing which of the many thin-walled 10% coronary plaques are vulnerable, we still have a lot that we can do. Note the pronoun, we.

Heart disease therapy means addressing a diffuse disease. It means reducing both the number of plaques and their vulnerability. Ultimately, this is about lowering inflammation. First comes lifestyle. Remember the four legs of the table of health: good food, good exercise, good sleep and good attitudes. Eating less insulin-spiking sugar, inflammatory trans-fats and fewer calories lowers inflammation. The emerging understanding of the importance of gut bacteria gives credence to the saying, we are what we eat. Nutrition is not complicated: eat real food when you are hungry. Exercising every day that you eat soothes the mind, conditions the heart and keeps the body from accumulating fat. Our bodies are beautiful; it’s tragic when humans don’t use their bodies. Getting high quality sleep lowers inflammation. You don’t need me to tell you how good it feels to sleep well. Finally, I’d bet every bike I own that compassion, grace and optimism soothe the vulnerable plaque.

After lifestyle comes medical therapy. Statin drugs don’t prevent heart attacks, strokes and death by lowering cholesterol; that’s just something we humans can easily measure. Statin drugs improve outcomes in patients with established heart disease by reducing inflammation at the arterial wall/blood interface. Beta-blockers and ACE-inhibitors (and ARBs) aren’t just simple blood pressure lowering agents. They have important activity on the neuro-hormonal milieu of the diseased heart and blood vessel. And simple aspirin therapy goes a long way in preventing platelets from accumulating on vulnerable plaques. Science confirms that these classes of drugs lower event rates in patients with established heart disease or those at high-risk of heart disease. I call them the big four heart medications. (BTW: they are all generic!)

Heart disease treatment, however, remains a team sport. Doctors can’t do it alone. Right now, there’s far too much emphasis on treating a diffuse disease with focal therapies. Stents may improve blood flow; bypass surgery may provide a brief reprieve; ICDs offer some protection to selected patients, but it will always be about lowering inflammation. There’s no pill or stent or ICD for that.

JMM