The Heart Healers (37 page)

Tom argued that although their chest pain was relieved, there was no evidence that they lived longer. He insisted that “as it is now practiced, its net effect on the nation’s health is probably negative. Fully half of the bypass operations performed in the United States are unnecessary.”

Preston accused the entire cardiologic community of bias, claiming that we refused to do a clinical trial because we “knew” that our patients would die without the surgery. In simple language, he was saying, “prove it saves lives.” Preston’s comments on angioplasty were similar, and equally scathing.

Preston’s critique of our two “revascularization” procedures infuriated its practitioners. Some refused to talk to him. How could he examine patients, observe their dramatic relief of pain, see X-ray pictures of blood pulsing through the heart’s arteries, and then conclude that revascularization would not prolong life? By being rigidly illogical, he was raising unnecessary fears and questions in patients’ minds. Let the rain fall on him up there in Seattle, he was not going to rain on our parade. My colleagues in Los Angeles privately labeled Preston “the Anti-Christ of Angioplasty.”

A few years later came the stunning results of the first randomized trials of revascularization (bypass surgery and angioplasty) versus medical management. Although revascularization relieved angina, it turned out that neither had much effect on either the heart attack rate or the mortality rate in patients with stable angina. Mason Sones’s X-ray images of the heart’s arteries had become cardiology’s Rorschach test. We had acquired an “occulo-stenotic reflex”: if we saw narrowing in an artery our instant reflex response was to dilate it. Tom Preston had seen the elephant in the room; somehow it had escaped our notice.

Heart attacks were proceeding unabated in people even after bypass surgery and angioplasty, when our patients had been relieved of angina. How could it be that we were relieving chest pain, restoring the blood supply, but not prolonging life? It made no sense. We needed to return to first principles. We were missing something. And whatever it was, it was a crucial detail about CAD. As we will see, it is the one detail you must know to avoid a heart attack.

*   *   *

FOR A MEMBER
of the high-IQ club Mensa, Jim Fixx did some dumb things as an early adult. His father had his heart attack at age thirty-five and died at age forty-three. As Jim turned thirty-five, he weighed 240 pounds and smoked two packs of cigarettes per day. Then at age thirty-five he got wisdom. He decided to get in better shape. He began running. At age forty-five, he had stopped smoking, and lost sixty pounds. He published a well-researched book about the health benefits of running. His book,
The Complete Book of Running
, made it to the
New York Times
bestseller list and stayed there for almost two years, selling over a million copies. Jim became a regular guest on TV talk shows. He was hailed as a pioneer in America’s fitness revolution, promoting the health benefits of regular exercise in middle age.

But it was too late. On July 20, 1984, at age fifty-two Jim did his daily ten-mile run along on a rural Vermont road. He stopped at a grassy hill about forty yards from the door of his motel. Jim’s knees buckled; he slumped to the ground. Jim Fixx died at that spot in his jogging suit. Autopsy showed atherosclerosis in all three coronary arteries. Atheroma had narrowed one coronary artery by 95%, a second by 85%, and the third by 70%.

Jim had played a vigorous singles tennis match the day before his death. He had never complained of cardiac symptoms. As his former wife, Alice Fixx, said, “He never had any warning.”

Jim’s death exposed gaping holes in our approach to CAD. First, since entering the period of life when CAD makes its first appearance he had spent seventeen consecutive years following a healthy diet, combined with regular vigorous exercise. When had his severe three-vessel CAD begun? We had no good idea. Second, half of CAD-related sudden deaths occur in people like Jim Fixx, who had no prior symptoms. We were performing hundreds of thousands of bypass surgeries and angioplasties each year on people with symptoms. Both procedures relieved chest pain (angina) in the vast majority of cases. If we had known the obstructions were present in Jim Fixx’s arteries could we have prevented his heart attack by angioplasty or bypass surgery? To solve these conundrums we needed to determine when, why, and how obstructive atheromas (cholesterol plaques) form in coronary arteries. What we discovered is crucial knowledge for anyone with heart disease in their family, because it provides your foundation for preventing CAD.

*   *   *

IN SCIENCE, GREAT
ideas spring from great contradictions. An inexplicable paradox had erupted like crabgrass in our perfectly manicured lawn. Seeing atheromas disappear after angioplasty, we had made science’s critical error, the logical assumption. If CAD was a disease caused by a mass that obstructed blood flow, then surely it followed that eradicating the obstruction and restoring flow would cure the disease. And yet it did not. It defied logic that we were opening narrowed vessels and bypassing obstructions but not having an impact on the rate of heart attacks. From patients who had angiograms before and after their heart attack, we realized that the coronary angiogram failed to predict which atheroma would rupture, and consequently where or when a heart attack will occur. Think of it this way: the angiogram reliably identifies a block in the road but it does not tell us where the avalanche would occur. In admitting this paradox we exposed humbling lacunae in our knowledge. Angioplasty for prevention of heart attack teetered uneasily on its pedestal. We had to admit we had only a rudimentary understanding of our lethal adversary, the atheroma. The time had come to fling open the long-shuttered windows on atherogenesis—how atheromas form.

The quest to understand atherogenesis was not new. Early pathologists had begun by simply describing what they saw. When we slice open a normal coronary artery lengthwise, we see a lovely smooth glistening pink surface punctuated by the openings of branch vessels. The blood vessel surface is slick to our touch. Now let’s place an atherosclerotic vessel next to it. Diseased vessels are pocked by irregular yellow bulges that make the surface bumpy. In some cases we see little red hemorrhages beside the bulges. Think of pizza. The pathologists do when they gaze on the irregular conflagration of yellows, oranges, and reds. When the yellow protrusions bulging into blood vessel surface are sliced open, they extrude a heavy slippery substance that reminded early pathologists of the gruel they had for breakfast. To bestow the aura of science on their work pathologists called their discovery an atheroma, from the Greek
athera
meaning gruel and
oma
meaning tumor. They also saw that calcium was added to the gruel-tumor over time, making the previously soft and flexible blood vessel stiff and inflexible. More erudition was necessary: they added
sclera
(Greek for rigid) and
osis
(Greek for condition). Atherosclerosis is the pseudo-erudite term for atheroma-induced hardening of the arteries. The word tells us what we see, but gives us no insight about cause.

Three competing theories of atheroma formation emerged. In the mid-1800s the century’s most brilliant pathologist, German Rudolph Virchow, identified both cholesterol crystals and inflammatory cells in atheroma. Virchow thought inflammation was the trigger, proposing “inflammation hypothesis.” Against him stood those who thought atheroma formation began with cholesterol accumulation, the “lipid hypothesis.” Still others thought the process was more like wrinkles, simply a natural outcome of aging, the “senescence” hypothesis. The battle to understand the nature of our tiny adversary was joined. The three hypotheses framed a scientific battle that consumed much of the next century. Which hypothesis would be proven correct?

Just before World War I, Russian pathologist Nikolai Anitschkov succeeded in creating atheromas in rabbits by feeding them purified cholesterol, sixty-one egg yolks over seventy days in one protocol. Animals fed cholesterol-free sunflower oil remained free of atheromas. For the next thirty years, Anitschkov used his microscope to lay out the progression of atherosclerosis for the world to see. He found that young lesions were reversible, but older, more complex lesions were not. Although he toiled in isolation in St. Petersburg he published in both Europe and the United States. A searing irony is that the work of the man who clearly described atheroma formation was unappreciated in his lifetime because of a quirk of geography. Even today although historians know of his work, his name is largely unrecognized in the modern world of Western cardiology. He was ignored, at least in part because existing Western dogma favored the senescence hypothesis.

The rejection of Anitschkov, however, was also promoted by Mother Nature. When other investigators set out to validate his claims, they reached for their standard laboratory animal, the dog. The cholesterol-fed dog, however, does not develop atherosclerosis. In carnivores like the dog, unlike rabbits and man, blood cholesterol is rapidly transferred to bile and excreted. With no elevation of blood cholesterol, no atheromas develop. For Anitschkov’s skeptics, the rabbit model was simply too remote from the human condition. His cholesterol-fed rabbits had blood cholesterol levels two to five times that of humans, and their atheromas developed over weeks or a few months, whereas human disease only appeared in middle age. To the medical establishment of his day, Anitschkov was a scientific Dostoyevsky, a long-winded Russian who had created too many complex questions and not enough easy answers.

At the end of World War II, the preponderance of erudite medical opinion rejected the “lipid hypothesis” that cholesterol was the cause of CAD. Cholesterol advocates were too much hypothesis and too little fact, all hat and no cattle. In the 1946 edition of
Quantitative Clinical Chemistry,
that era’s biochemistry bible, John Peters and Donald Van Slyke concluded that “although there can be no doubt that deposits of lipids, especially cholesterol, are consistent and characteristic features (of atherosclerotic lesions) there is no indication that hypercholesterolemia plays more than a contributory role in their production.” Instead, pathologists supported the “senescence hypothesis.” Atherosclerosis, death, and taxes were inevitable, even though atherosclerosis and death didn’t get worse each time Congress met.

Faced with the emerging epidemic of CAD and no understanding of its pathogenesis, in 1948 the National Heart Institute made a decision that reverberates through the halls of academia today, sixty-five years later. They set out to define the risk factors that predicted the appearance of CAD in apparently normal people. The concept was to identify a relatively small town, collect all the known potential risk-factor information in all its citizens, and then follow them until death. The Framingham Heart Study is named after the town that was chosen. Framingham, Massachusetts, was an ideal site for a long-term epidemiology study, a typical small American town, midway between Boston and Worcester, where people were begotten, born, and died. The Framingham study continues today with the progeny of the original participants. Each participant’s age, sex, blood pressure, cholesterol, body mass, smoking history, family history, and diabetes were recorded (later the cholesterol subfractions, good and bad cholesterol, were added). Then investigators sat back and waited for subsequent development of CAD. When the ten-year follow-up results became available in the mid-1960s, it was used to create charts that estimated the ten-year risk for developing the symptoms of CAD. When I discuss risk and lifestyle modification with a patient, I refer to the Framingham results, which provides a sense of the risk of disease and the benefit of therapy, always adding Einstein’s caveat that, “Not everything that can be counted counts, and not everything that counts can be counted.” The Framingham model, for instance, does not include genetic history as a risk factor.

At about the same time, University of Minnesota nutritionist Ancel Keys began a study that approached atheroma formation from a different perspective. Keys hypothesized that since cholesterol is a form of fat, the amount of fat in diet might determine who gets CAD. He collected data on the type and amount of fat in seven different countries’ diet, the average blood cholesterol, and the cardiac death rate. Not surprisingly, Japan with its emphasis on fish consumption had the lowest blood cholesterol level at 160 mg/dl. Finland, with very high dairy fat consumption, had the highest, 260 mg/dl. Then came the jaw-dropping result: the ten-year heart attack death rate was a paltry 5 out of 1,000 men in Japan but a whopping 70 out of 1,000 in Finland, a fourteenfold difference. The remaining five countries had intermediate cholesterol levels and death rates. The data for all countries almost fit a straight line, suggesting that risk of death was proportional to the level of blood cholesterol. Then Keys brandished a second graph that was to influence Western eating habits to this day: the blood cholesterol level was proportional to the amount of saturated fat in the diet. The difference in fat intake was as stunningly different as the death rate. In Finns, saturated fats constituted about 20% of daily calories, whereas in Japanese it was only 3%. Again, the values for the other countries fell roughly along a straight line.

Keys drew this logical, stunning conclusion: dietary saturated fat raises blood cholesterol and in turn, cholesterol increases the risk of a fatal heart attack. Keys’s study breathed new life into Anitschkov’s lipid hypothesis. In the mind’s eye it was an easy leap from Anitschkov’s atherosclerotic rabbit munching cholesterol chow to a fat Finn toppling over after devouring a plate of Gouda cheese.

The Framingham study and the Seven Countries Study precipitated the Cholesterol War. Every producer of fat, from farmers with cholesterol-laden egg yolks to ranchers with fat pigs, fought back. Their scientific surrogates howled that Keys had marched from preconceived notion to foregone conclusion. He had not conducted his study to find the truth; he had done it to prove a point. He was biased. Further, they insisted that an association between two measurements does not establish causality. Keys might just as well have shown that family telephone bills cause auto accidents. Sure, telephone bills and auto accidents correlate, they argued, but correlation is not cause. Teenagers increase both the phone bill and the accident rate. The difference between the Finns and Japanese could be due to obesity or to different smoking rates, or any other unrecognized factor. The study, they concluded, was hogwash.