The Origins of the Cholesterol Con

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By Maggie Mahar, Health Beat

The widespread belief that "bad Cholesterol" ( LDL cholesterol) is a major factor driving heart disease -- and that cholesterol-lowering drugs like Lipitor and Crestor can protect us against fatal heart attacks -- is turning out to be a theory filled with holes. These drugs, which are called "statins," are the most widely-prescribed pills in the history of human medicine. In 2007 world-wide sales totaled $33 billion. They are particularly popular in the U.S., where 18 million Americans take them.

We thought we knew how they worked. But last month, when Merck/Schering Plough finally released the dismal results of a clinical trial of Zetia, a cholesterol-lowering drug prescribed to about 1 million people, the medical world was stunned. Dr. Steven E. Nissen, chairman of cardiology at the Cleveland Clinic called the findings "shocking." It turns out that while Zetia does lower cholesterol levels, the study failed to show any measurable medical benefit. This announcement caused both doctors and the mainstream media to take a second look at the received wisdom that "bad cholesterol" plays a major role in causing cardiac disease. A Business Week cover story asked the forbidden question, "Do Cholesterol Drugs Do Any Good?"

The answer, says Dr. Jon Abramson, a clinical instructor at Harvard Medical School, and the author of Overdosed America, is that "statins show a clear benefit for one group -- people under 65 who have already had a heart attack or who have diabetes. But," says Abramson, "there are no studies to show that these drugs will protect older patients over 65 -- or younger patients who are not already suffering from diabetes or established heart disease from having a fatal heart attack. Nevertheless, 8 or 9 million patients who fall into this category continue to take the drugs, which means that they are exposed to the risks that come with taking statins -- which can include severe muscle pain, memory loss, and sexual dysfunction."

Finally -- and here is the stunner -- it turns out we don't have any clear evidence that statins help the first group by lowering cholesterol levels. It's true that they do lower cholesterol, but many researchers are no longer convinced that this is what helps patients avoid a second heart attack. It now seems likely that they work by reducing inflammation. In other words, these very expensive drugs seem to do the same thing that aspirin does. (Are they more effective than the humble aspirin? We'll need head-to-head studies to find out.)

In the past, some physicians have questioned the connection between high cholesterol and heart disease. After all, as Dr. Ronald M. Krauss, director of atherosclerosis research at the Oakland Research Institute, told Business Week, "When you look at patients with heart disease, their cholesterol levels are not that [much] higher than those without heart disease ... Compare countries, for example. Spaniards have LDL levels similar to Americans, but less than half the rate of heart disease. The Swiss have even higher cholesterol levels, but their rates of heart disease are also lower. Australian aborigines have low cholesterol but high rates of heart disease."

Why then, were we all so certain that LDL cholesterol led to fatal heart attacks? The truth is that we were not "all" so sure. Within the medical profession, there have always been skeptics -- particularly in the U.K. But in the U.S., the Popes of cardiology, the American Heart Association and the College of Cardiologist each put their imprimatur on the cholesterol story, insisting on its truth, until finally, it became dogma.

As science writer Gary Taubes pointed out in a recent New York Times Op-ed: "The idea that cholesterol plays a key role in heart disease is so tightly woven into modern medical thinking that it is no longer considered open to question." Taubes, whose work has appeared in The Best American Science Writing, Science, and the New York Times Magazine, explains that "because medical authorities have always approached the cholesterol hypothesis as a public health issue, rather than as a scientific one, we're repeatedly reminded that it shouldn't be questioned. Heart attacks kill hundreds of thousands of Americans every year, statin therapy can save lives, and skepticism might be perceived as a reason to delay action. So let's just trust our assumptions, get people to change their diets and put high-risk people on statins and other cholesterol-lowering drugs."

Taubes sees things differently. "Science suggests a different approach: Test the hypothesis rigorously and see if it survives." But when it comes to the cholesterol theory, this is what never happened. Go back to 1950, and you will understand why.

As the second half of the twentieth century began, public health experts were flummoxed by the steep rise in heart attacks. Turn-of-the century records suggest that heart disease caused no more than 10 percent of all deaths -- many more people died of pneumonia or tuberculosis. But by 1950, coronary heart disease, or CHD, was the leading source of mortality in the United States, causing more than 30 percent of all deaths.

One common-sense explanation comes to mind: With improved sanitation, plus new drugs, fewer people were dying of infectious diseases. So they were living long enough to die of a heart attack.

But to many, that didn't seem sufficient. So in 1949, the National Heart Institute introduced the protocol for the Framingham Study. The research, which began in 1960, set out to investigate the factors leading to cardiovascular disease (CVD) and began with these hypotheses:

1. CVD increases with age. It occurs earlier and more frequently in males.

2. Persons with hypertension developed CVD at a greater rate than those who are not hyper-tensive.

3. Elevated blood cholesterol level is associated with an increased risk of CVD.

4. Tobacco smoking is associated with an increased occurrence of CVD.

5. Habitual use of alcohol is associated with increased incidence of CVD.

6. Increased physical activity is associated with a decrease in the development of CVD.

7. An increase in thyroid function is associated with a decrease in the development of CVD.

8. A high blood hemoglobin or hematocrit level are associated with an increased rate of the development of CVD.

9. An increase in body weight predisposes to CVD.

10. There is an increased rate of the development of CVD in people with diabetes mellitus.

11. There is higher incidence of CVD in people with gout.

Other factors were later added to the list, including HDL and LDL lipid fractions.

Ultimately, "the Framingham study determined that higher total cholesterol levels significantly correlate with an increased risk of death from coronary heart disease only through the age of 60" observes "Evidence for Caution: Women and Statin Use," a well-documented 2007 report from The Canadian Women's Health Network. Moreover, the research showed that cholesterol was only one of many factors leading to CVD for younger patients.

...rest of article.

Maggie Mahar is a fellow at The Century Foundation and the author of Money-Driven Medicine: The Real Reason Health Care Costs So Much (Harper/Collins 2006).

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It is my opinion one cannot simplify the LDL argument to the point of just cholesterol versus the effects one drug has on its levels. Regulation of cellular metabolism has more than just one pathway to do away (or modify for actual use) with cholesterol so I wouldn't be shocked if the scientific methodologies of these patient-driven clinical trials are reworked so as to pinpoint the actual pathways involved, downregulated, and upregulated with statin activity.

The fact of the matter is that we as a society needs to focus on the aspect of preventing hypercholesteremia.

And even that is not as simple. Remember that there is inherited hypercholestermia and against genetics there are not as many easy answers sometimes.

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Simply put, we need to have more people getting honors in school. Quit fighting that school means nothing and that experience matters. School gives you the tool you need to analyze things. That is how we prevent these hyper-disorders.

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It is my opinion one cannot simplify the LDL argument to the point of just cholesterol versus the effects one drug has on its levels. Regulation of cellular metabolism has more than just one pathway to do away (or modify for actual use) with cholesterol so I wouldn't be shocked if the scientific methodologies of these patient-driven clinical trials are reworked so as to pinpoint the actual pathways involved, downregulated, and upregulated with statin activity.

The fact of the matter is that we as a society needs to focus on the aspect of preventing hypercholesteremia.

And even that is not as simple. Remember that there is inherited hypercholestermia and against genetics there are not as many easy answers sometimes.

That's understandable. I think the author is coming from the angle that billions of dollars are being spent on prescription drugs that have not been rigorously tested, but have been accepted as safe and effective.

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Totally agreeable logic. This country's pharmaceutical industry makes it a very common point to push the marketing aspect of its products rather than the actual therapeutic benefits. Obviously the drugs are regulated and when not enough patients meet the threshold for having positive effects, then the FDA steps in to bring down the drug as an option for suitable use. I just crack up when off-label uses become commonly used after MDs receive 'seminars' from company reps...