The Framingham Study

George Mann, who came to the field in the early 1960s, achieved a remarkable degree of success before he mired himself in controversy by studying the Masai. He was, in fact, an associate director for one of the most famous heart disease investigations ever undertaken: the Framingham Heart Study. Framingham is a small town near Boston, Massachusetts, that has been a virtual petri dish for the study of heart disease since 1948. Now on its third generation of research subjects, it began with some five thousand middle-aged men and women who took part in a survey of every factor researchers could think of that might play a role in the development of heart disease. Participants subjected themselves to comprehensive physicals, interviews, and follow-up tests every two years. It was the first large-scale attempt to find out whether risk factors such as cigarette smoking, high blood pressure, and genes might reliably predict death from heart disease.

In 1961, after six years of study, the Framingham investigators announced their first big discovery: that high total cholesterol was a reliable predictor for heart disease. This is considered one of the most significant findings in the history of heart disease research because before then, even though experts had come to assume serum cholesterol was bad, the evidence was only circumstantial.

The news had broad implications. For one, it solved a problem that had plagued heart disease research from the start, namely, that investigators needed something they could measure to assess heart attack risk before death. It may seem callous to say, but when trying to detect the cause of disease, death is the ideal end point to study. Researchers prefer to follow subjects, looking at what they eat, whether they smoke, and other factors, until they die. Death is the “event,” or “hard end point,” in the language of research; it is the indisputable data at the end of an experiment. (Heart attacks are also considered “hard” end points, but even these are subject to diagnostic uncertainty, as we’ve seen.) Looking back from the undeniable fact of death, researchers can then ask, “Was it how much bacon they ate, or the cigarettes, or something else?”

Waiting for subjects to die, however, means that researchers are burdened with following a population over many years. Finding an “intermediary” or “soft” end point to measure before death has therefore been the subject of a great science hunt. If an indicator could reliably predict heart disease, researchers could run shorter experiments and measure those intermediary factors instead. The identification by Framingham of total cholesterol as a soft end point was therefore seen as a breakthrough for the field: scientists could now presumably conclude that any food that raised total cholesterol would also increase the risk of a heart attack. In all likelihood, doctors could use this factor in helping patients to identify their coronary risk as well.

The Framingham finding about cholesterol was thus highly important. And above all, it seemed to erase any lingering doubts that researchers might have had about the diet-heart hypothesis. William Kannel, the medical director of Framingham, was quoted in a local newspaper as saying, “That blood cholesterol is somehow intimately related to coronary atherosclerosis is no longer subject to reasonable doubt.”

However, thirty years later, in the Framingham follow-up study—when investigators had more data because a greater number of people had died—it turned out that the predictive power of total cholesterol was not nearly as strong as study leaders had originally thought. For men and women with cholesterol between 205 and 264 milligrams per deciliter (mg/dL), no relationship between these numbers and heart disease risk could be found. In fact, half of the people who had heart attacks had cholesterol levels below the “normal” level of 220 mg/dL. And for men aged forty-eight to fifty-seven, those with cholesterol in the midrange (183–222 mg/dL) had a greater risk of heart attack death than those with higher cholesterol (222–261 mg/dL). Total cholesterol turned out not to be a reliable predictor for heart disease after all.

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The Framingham data also failed to show that lowering one’s cholesterol over time was even remotely helpful. In the thirty-year follow-up report, the authors state, “For each 1% mg/dL drop of cholesterol there was an 11% increase in coronary and total mortality [italics added].” This is a shocking finding, the very opposite of the official line on cholesterol lowering. Yet this particular Framingham finding is never discussed in scientific reviews, even though many large trials have found similar results.

Other important findings from Framingham have also been ignored, including—notably—those on dietary risk factors, which were examined in the part of the study that Mann conducted. Together with a dietician, Mann spent two years collecting food-consumption data from one thousand subjects, and when he calculated the results in 1960, it was very clear that saturated fat was not related to heart disease. Concerning the incidence of coronary heart disease and diet, the authors concluded, simply, “No relationship found.”

“That went over like a wet blanket with my superiors at NIH,” Mann told me, “because it was contrary to what they wanted us to find.” The NIH also generally favored the diet-heart hypothesis from the early 1960s on, and “they wouldn’t allow us to publish that data,” he says. Mann’s results lay in an NIH basement for nearly a decade. (To withhold scientific information “is a form of cheating,” Mann lamented.) And even when the findings eventually came out in 1968, they were so deeply buried that a researcher has to dig through twenty-eight volumes to find the news that variations in serum cholesterol levels could not be traced back to the amount or type of fat eaten.

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- Nina Teicholz - page 64