The Heart Healers (39 page)

Think about the implication of this insight for treatment of CAD. It is why half of the Framingham heart attack victims had no symptoms prior to their heart attack. The ruptured plaque was too small to cause angina before it ruptured. And that leads to a second stunning insight: it is impossible to greatly reduce heart attacks if you only put a stent across a large atheroma. A swarm of smaller Judases still lurk in the artery, ready to betray their master and cause a heart attack.

Every society and every generation casts disease in its own image. Anthropologist Meira Weiss finds that cancer patients view the malignancy as a Pac-Man chomping everything it encounters, a beautiful fruit with worms inside, or an octopus with sticky tentacles. AIDS, affecting the whole body, is seen as diffuse, decaying, and polluting, as amorphous as an amoeba engulfing its prey, as fluid as Dali’s melting clocks. Metaphors for heart disease are far less lyrical. Heart disease is a something that needs fixing, like a piston pumping in a misshapen cylinder, a rusted pipe. Interventional cardiologists call themselves plumbers. But we chose the wrong metaphor. Coronary arteries are not rusting pipes. Heart attack cannot be prevented by performing angioplasty on one atheroma among the many that dot the surface of the blood vessel. One of those atheromas is a quiescent volcano, ready to erupt without warning. So angioplasty and bypass surgery are highly effective for relief of angina, but not for preventing heart attacks. The essential insight for patients is that prevention of heart attack requires a different therapy.

Our new understanding of the birth, adolescence, and maturity of our tiny terrifying assailant bought a stunning irony. We had known our adversary intimately, because we had once stared him in the face. Literally. In our teen years, from time to time the tiny fat secreting units in our skin, called sebaceous follicles, become obstructed. Fat is trapped beneath our skin. The trapped fat is oxidized, inducing a violent inflammatory response. The skin becomes red and tender. Driven by inflammation, the fat erodes to the surface of the skin and pops out. When it ruptures, a tiny blood clot forms at the site. We call it a pimple.

The ruptured atheroma is the identical process, but it occurs in the coronary artery. Fat (in this case, cholesterol) gets trapped beneath the surface of the blood vessel. It is oxidized. The ensuing violent inflammatory response causes it to burrow its way relentlessly toward the vessel surface. Both the pimple and the atheroma erupt like a packed garbage bag tossed into a busy street, spewing its contents on its environment. And when the atheroma bursts, just like a pimple, a blood clot forms at the site of rupture.

An atheroma is as simple as a pimple on the blood vessel wall. Who could possibly have imagined that? All we can say is that sometimes our physiology is not only queerer than we imagine, but queerer than we can imagine. As one of my students asked after I explained atherogenesis, “Do you mean to say that this century’s leading cause of death is acne?”

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MY PASSAGE FROM
callow young clinical investigator to cardilogic leadership had moments of exhilaration and despair. Many of my mentees returned to become leaders in cardiology. They invited me to their cities and homelands as a visiting professor. I was fascinated to see the vast differences in medical practice around the world, An unanticipated secondary benefit was that my wife and I always added a few extra days to travel through most of Asia, Europe, the Middle East, and South America. When I was home my trainees allowed me, like my dad before me, to never miss my three sons’ baseball and soccer games.

My low point in those years came when my eighty-seven-year-old father called me from his home about thirty miles south of Albuquerque, New Mexico. He had awakened with severe substernal chest pain and shortness of breath in the middle of the night. It had disappeared after a half hour, then he had two more episodes in the ensuing hours. His medical history was unremarkable other than the diagnosis of mild Alzheimer’s disease. He had no history of CAD, had never smoked, was not diabetic, and had never had high blood pressure. He was not sure what his cholesterol level was, but he was not taking any medications. But substernal chest pain with associated shortness of breath in an eighty-seven-year-old still says CAD.

I called my friends Drs. Michael Crawford and Jonathan Abrams, who were then the current and past chiefs of cardiology at the University of New Mexico. We arranged for an ambulance to take my father to the hospital. Mike called me at about midnight after examining Dad in the emergency room of Presbyterian Hospital and said, “Jim, he has no chest pain at the moment, but he does have ECG changes that indicate CAD, and his blood work indicates he has had some minimal muscle damage. So with the recent history of stuttering chest pain, I think we can be sure that your dad has a ruptured plaque causing unstable angina. What’s your thinking about what to do next?”

I went blank as a segment of my mind told me I knew nothing at all about what to do, that I was unqualified to make such a decision. For a few moments I was the helpless student in Philadelphia, thrust back in the cruel world of medical uncertainty, where there are no clear-cut answers. Then I regained my balance. I knew how we approached decisions. Unstable angina is a condition midway between stable angina and heart attack. Patients with the symptoms of unstable angina have a vastly different prognosis depending on other factors. About a decade ago, Harvard’s research team identified seven risk factors that predicted adverse outcomes during hospitalization for unstable angina. The more factors a patient has, the more likely the partially occlusive clot in the coronary artery is to become completely occlusive; the more likely an unstable angina patient is to have a full-blown heart attack. People with only one factor have about a 5% risk; those with six or seven factors have an eightfold greater risk of going on to a heart attack.

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IN THE EMERGENCY
room we can stratify our patients into low, intermediate, or high risk. As a rule of thumb we treat low-risk patients with drugs and observation, and send high-risk patients (who have more than four factors) promptly to the cath lab. The strategy is based on outcomes. In low-risk patients, medical therapy is at least as good as angioplasty, whereas in high-risk patients, angioplasty is clearly superior. Dad had three factors, so he had an intermediate risk. And so our first wrenching decision: should Dad have medical therapy or angiography?

Mike and I agreed that we could treat Dad with medical therapy under close observation and hope that he stabilized.

In the morning Dad continued to have episodes of pain despite drugs to inhibit clot formation and dilate his coronary arteries. Failure to respond to therapy catapults a patient into the high-risk category. Mike and I agreed that we had to send Dad to the cath lab to see his coronary arteries. Hours later I got a call from the cath lab. It was the worst of all possible news. Dad had an atheroma in his left main coronary artery. It was only about 50% obstructive, but it seemed to be the lesion that had ruptured to precipitate unstable angina. Dad had three options: angioplasty of the left main coronary artery, bypass surgery, or continued medical management. All three choices were unappealing. Let’s look at each.

Many cardiologists at that time would not perform balloon angioplasty on the left main coronary artery because it carried about a 5% risk of immediate procedural mortality. But beyond the immediate risk is the problem created by putting a metal stent in the vessel. After stent placement the patient should probably take an anticlotting drug for a year. The risk of a blood clot forming on the exposed metal skyrockets if a patient stops the drug. So we avoid stents in people who cannot be relied upon to take the drug religiously, like drug addicts, psychiatric patients, and of course patients with Alzheimer’s disease. For Dad, a clot that formed on a left main stent would almost certainly be fatal. The anticlot drugs also increase the risk of bleeding, and markedly so in an elderly patient. Elderly people fall a lot, and a fall with a broken hip while on anticlotting drugs can represent a big problem. So angioplasty was unappealing.

What about surgery? Mike and I both felt that Dad would survive the procedure. We can operate on eighty- and ninety-year-olds, and Dad was in good health except for his brain and now his heart. But the problem with surgery in this age group is that it carries as much as a 5% risk of stroke, and perhaps a 20% risk of measurable decline in brain function. In younger patients, the decline typically disappears in months. But Dad already had impaired mental function. Surgery could accelerate his descent into Alzheimer’s, robbing him of the remaining meaningful time he still had left.

And medical therapy? Should we continue with just drugs and bed rest when the treatment had already failed to control his symptoms? Should we hope that the partially occlusive clot in his coronary artery would regress with time, rather than progress to complete occlusion, knowing that if it progressed to occlusion it would undoubtedly be fatal? The risk of progression to infarction was significant. In the days before angioplasty and bypass surgery, we had called unstable angina “preinfarction angina” because about 20% of our patients went on to have a full-blown heart attack. As an eighty-seven-year-old, his risk was probably even higher. If Dad was sixty-five years old with no Alzheimer’s disease, medical therapy would have been my third choice. But he was eighty-seven years old with Alzheimer’s disease. Which course of therapy would you choose for your father? I will let you struggle with the decision for a few minutes while we return to put the atheroma formation and plaque rupture in broader perspective.

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BOTH STABLE PLAQUES
and vulnerable (ready to rupture) plaques are accidents of evolution. Our primeval ancestors were plant eaters, herbivores with no atheromas in their blood vessel walls. To counter periodic famine, however, they needed an energy storage system. Our ancestors were selected for survival because of their ability to store life-sustaining energy in the form of fat. With the emergence of civilization, our diet changed. When we began consuming vast amounts of red meat and animal fat, we created what author Michael Pollan calls the Omnivore’s Dilemma. When the level of fat in our bloodstream exceeded the capacity of its transport system, some of the fat that entered the blood vessel wall got left behind. The stable plaque, the cause of chest pain on exertion, is the bastard child of a mechanism originally designed for survival.

Two of Nature’s other essential lifesaving processes create the vulnerable plaque. At the heart of plaque rupture lies inflammation. The inflammatory response was developed at least 500 million years ago, as the sole immune defense weapon of most primitive multicellular organisms. It is so important to survival that it has been conserved throughout evolution of every species all the way to man. Introduce into your body anything that the immune system identifies as foreign, and you precipitate what we call the foreign body response. You have seen this response in your own skin with bacteria (an infected hangnail), fat (the pimple), or even a wood splinter. Yet when the fury of inflammation persists in any tissue for long periods of time, it changes from becoming beneficial to potentially lethal. In blood vessels, the inflammatory response to oxidized fat is responsible for erosion through the blood vessel’s inner surface until the plaque ruptures. The pimple bursts.

Clotting at sites of blood vessel damage has saved the life of each of us. The tiny atheroma, however, managed to turn both inflammation and blood clotting upside down, Humpty Dumpty, and by so doing, it became potentially lethal. Nature has decreed that three mechanisms, which made survival possible—energy storage, inflammation, and blood clotting—would return to complete the circle of human life as our leading cause of death. Sunrise and sundown.

By the millennium, cardiology had consumed a century bantering over competing hypotheses of atherosclerosis. Like the blind men examining the elephant, we had seen different manifestations of the same beast. Finally, however, cardiology found its Grand Unifying Theory. The lipid hypothesis explains atheroma formation, the inflammation hypothesis explains atheroma rupture, and the senescence hypothesis explains the atheroma’s long lifetime. Everybody was right.

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WHICH TREATMENT DID
you choose for my dad? Balloon angioplasty with a 5% risk of death on the table, survivable surgery with a 20% likelihood of further mental deterioration, or drugs which had thus far been ineffective in a patient at 30% risk of going on to a heart attack? Mike and I chose the medical option for Dad. We felt that the immediate risk of death and the long-term risk of missed drug doses and bleeding ruled out angioplasty. We decided against surgery because we feared further devastating mental deterioration. Perhaps I also felt that if either of these interventions failed, we would bear responsibility, whereas if Dad passed away on medical therapy, it would be the disease, not our therapy that was responsible. But deep down I knew that as a cardiologist, from the first moment I joined in the decision-making, I was responsible for my dad’s outcome.

We made the right decision. In the next two days, Dad’s condition stabilized. He returned home. I visited him frequently, and called each week. As his Alzheimer’s disease progressed, my weekly calls became the high point of his week. I flew to visit him frequently.

At age ninety-three he fell, breaking his hip. After surgery, his mental condition never recovered; he was only sporadically able to recognize me. Dad passed away about a month after surgery, when a large blood clot dislodged from his leg and lodged in his lungs. Mike Crawford had given my father and his only son six good years together, far more than I hoped for on the night Dad called about his crushing chest pain. A moment that began for me as desperate uncertainty now stands as a treasured memory.

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