The Origins of the Cholesterol Con, Part II

[Guest guest]

http://www.healthbeatblog.org/2008/02/the-origins-of.html February 29, 2008The Origins of the Cholesterol Con, Part II Last week, I wrote about the “cholesterol con,” 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. 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 fractionsUltimately, “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.“Tales From the Other Drug Wars," a paper presented at a 1999 health conference in Vancouver, also stresses that “The Framingham Study actually found an association between blood cholesterol and coronary heart disease in young and middle-aged men only. No corresponding association was found in women or in the elderly, and it is in the latter group that most of the cases of heart disease occur.” And while the study linked blood cholesterol to heart disease in younger men, the study also found no association between dietary cholesterol (cholesterol. that comes from what we eat) and the risk of coronary heart disease, even in young and middle-aged men. “Dietary saturated fats were not associated with heart disease even after adjusting for other risk factors. Buried deep in the massive number of reports produced from the study is a quote from the investigators saying “…there is, in short, no suggestion of any relationship between diet and the subsequent development of coronary heart disease in the study group.” Many of the other factors that the Framingham Study investigated —including lack of physical activity, obesity, stress, smoking and alcoholism would prove very important, yet “for a variety of reasons,” the focus shifted to cholesterol” the 2007 Canadian report (“Evidence for Caution”) notes, which now “ has become the most prominent and feared risk factor for both women and men—perhaps because it is the most easily modifiable. By contrast there is no pill for the effects of air pollution, which is a substantial risk factor for heart disease, especially for women.”Thus began what the report calls “the “cholesterolization” of cardiovascular disease – that is, emphasis on a single risk factor. . . Cholesterol has come to represent a virtual disease state in itself, rather than one risk factor among many, and has distracted from grappling with other risk factors that are strong indicators of cardiovascular disease and cardiovascular risk.” Yet, as Taubes points out in his NYT Op-ed, the Framingham study did not support this conclusion: The researchers concluded that the molecules that carry LDL cholesterol (low-density lipoproteins) were only “ a’ marginal risk factor’ for heart disease” while the “cholesterol carried by high-density lipoprotein” actually “lowered the risk of heart disease.” “These findings led directly to the notion that low-density lipoproteins carry ‘bad’ cholesterol and high-density lipoproteins carry ‘good’ cholesterol,” Taubes explains. “And then the precise terminology was jettisoned in favor of the common shorthand. The lipoproteins LDL and HDL became ''good cholesterol' and 'bad cholesterol' and the molecule carrying the cholesterol was now conflated with its cholesterol cargo.“The truth is, we've always had reason to question the idea that cholesterol is an agent of disease,” says Taubes. “Indeed, what the Framingham researchers meant in 1977 when they described LDL cholesterol as a ''marginal risk factor'' is that a large proportion of people who suffer heart attacks have relatively low LDL cholesterol. “So how did we come to believe strongly that LDL cholesterol is so bad for us?” he asks. “It was partly due to the observation that eating saturated fat raises LDL cholesterol, and we've assumed that saturated fat is bad for us. This logic is circular, though: saturated fat is bad because it raises LDL cholesterol, and LDL cholesterol is bad because it is the thing that saturated fat raises.” Yet, he points out, “in clinical trials, researchers have been unable to generate compelling evidence that saturated fat in the diet causes heart disease. “The other important piece of evidence for the cholesterol hypothesis is that statin drugs like Lipitor lower LDL cholesterol and also prevent heart attacks. The higher the potency of statins, the greater the cholesterol lowering and the fewer the heart attacks. This is perceived as implying cause and effect: statins reduce LDL cholesterol and prevent heart disease, so reducing LDL cholesterol prevents heart disease. This belief is held with such conviction that the Food and Drug Administration now approves drugs to prevent heart disease, as it did with Zetia, solely on the evidence that they lower LDL cholesterol. “But the logic is specious because most drugs have multiple actions,” Taubes notes. “It's like insisting that aspirin prevents heart disease by getting rid of headaches.” Indeed, as noted above, many researchers now believe that statins help some cardiac patients the way aspirin help many cardiac patients: not by lowering cholesterol or by easing headaches, but by reducing inflammation. Nevertheless, in the 1950s, the theory that saturated fat and cholesterol from animal sources raise cholesterol levels in the blood, leading to deposits of cholesterol and fatty material in the arteries that, in turn, leads to fatal heart disease took off. It was called the Lipid theory, and before long food manufacturers would recognize just how much money there was to be made by promoting it. At the time there was relatively little profit to be made by trying to persuade Americans to stop smoking (smoking cessation clinics still don’t make anyone rich), and expensive gyms that encourage exercise had not yet become widely popular. But there was a fortune to be made by persuading Americans that if they ate foods low in saturated fats, they could live longer. “The Oiling of America,” a colorful history of the political campaign against animal fat by Mary Enig, a biochemist, nutritionist and former researcher at the University of Maryland, reports that in 1957 the food industry launched a series of ad campaigns that touted the health benefits of products low in fat or made with vegetable oils. A typical ad read: “Wheaties may help you live longer.” Wesson recommended its cooking oil “for your heart’s sake” and Journal of the American Medical Association ad described Wesson oil as a “cholesterol depressant.” Mazola advertisements assured the public that “science finds corn oil important to your health.” Medical journal ads recommended Fleishmann’s unsalted margarine for patients with high blood pressure. Dr. Frederick Stare, head of Harvard University’s Nutrition Department, encouraged the consumption of corn oil—up to one cup a day—in his syndicated column. In a promotional piece specifically for Procter and Gamble’s Puritan oil, he cited two experiments and one clinical trial as showing that high blood cholesterol is associated with CHD. Presumably, he was well paid for his work. Dr. William Castelli, Director of the Framingham Study was one of several specialists to endorse Puritan. Dr. Antonio Gotto, Jr., former AHA president, sent a letter promoting Puritan Oil to practicing physicians—printed on Baylor College of Medicine, The De Bakey Heart Center letterhead.The American Heart Association also pitched in. In 1956, a year before the food manufacturers' advertising blitz, an AHA fund-raiser aired on all three major networks, featuring Irving Page and Jeremiah Stamler of the AHA. Panelists presented the lipid hypothesis as the cause of the heart disease epidemic and launched the Prudent Diet, one in which corn oil, margarine, chicken and cold cereal replaced butter, lard, beef and eggs. (“Stamler would show up again in 1966 as an author of Your Heart Has Nine Lives, a little self-help book advocating the substitution of vegetable oils for butter and other so-called “artery clogging” saturated fats,” Enig points out in “The Oiling of America.” The book was sponsored by makers of Mazola Corn Oil and Mazola Margarine. Stamler did not believe that lack of evidence should deter Americans from changing their eating habits. The evidence, he stated, “was compelling enough to call for altering some habits even before the final proof is nailed down. . . the definitive proof that middle-aged men who reduce their blood cholesterol will actually have far fewer heart attacks waits upon diet studies now in progress.” And, of course, we still wait for that definite proof that middle-aged men who do not suffer from established heart disease nevertheless should be on statins.)“But the television campaign was not an unqualified success,” Enig continues, “because one of the panelists, Dr. Dudley White, disputed his colleagues at the AHA. Dr. White noted that heart disease in the form of myocardial infarction was nonexistent in 1900, when egg consumption was three times what it was in 1956 and when corn oil was unavailable. “But the lipid hypothesis had already gained enough momentum to keep it rolling, in spite of Dr. White’s nationally televised plea for common sense in matters of diet and in spite of the contradictory studies that were showing up in the scientific literature.”“The American Medical Association at first opposed the commercialization of the lipid hypothesis,” Enig reports, “ and warned that “the anti-fat, anti-cholesterol fad is not just foolish and futile. . . it also carries some risk.” The American Heart Association, however, was committed. In 1961 the AHA published its first dietary guidelines aimed at the public.” No doubt many researchers at the AHA were sincere. But it is worth noting that ultimately the AHA would find a way to turn the War Against Cholesterol into a profitable cottage industry. You’ve probably seen the AHA’s “heart check” logo on numerous food products. No surprise, they don’t give them out for free. Food manufacturers pay a first-year fee of $7,500 per product, with subsequent renewals priced at $4,500 according to Steve Millay, a biostatician, lawyer and adjunct scholar at the conservative Cato Institute, who posted about this on “junk science” in 2001. “There’s gold in the AHA’s credibility,” Milloy observed. “Several hundred products now carry the heart-check logo. You do the math. Adding insult to injury, consumers pay up for the more expensive brands that can afford to dance with the AHA. Pricey Tropicana grapefruit juice is ‘heart healthy’ but supermarket bargain brand grapefruit juice isn’t?” It wasn’t until 1987, when Merck produced the first statin, that the pharmaceutical industry began to get in on the action. But when it joined the party, it began to spread the money around, not only by advertising, but by paying well-placed cardiologists “consulting fees.” As I noted in last week’s post, when the National Cholesterol Education Program (NCEP) published new guidelines in 2004, urging that individual cholesterol levels be monitored from age 20 and that acceptable levels be significantly lower than was previously advised for prevention of cardio vascular disease in both women and men—whether or not they already suffered from established heart disease—eight of the nine doctors on the panel making the recommendations had financial ties to drug makers selling statins. They did not disclose this possible conflict of interested at the time. Both the American Heart Association and the American College of Cardiology endorsed the panel’s recommendation. At that point, the 2007 Canadian women’s study observes, the “ ‘cholesterization’ of heart disease intensified. Meanwhile, the study notes:“a year before the U.S. panel came out with the new guidelines, the AHRQ, the US agency that reviews the quality of healthcare research, produced a report on women and heart disease stating that there was insufficient evidence to determine whether lowering lipid levels by any method reduced the risk of heart attack or stroke in women, because women were under-represented in trials. “According to US research,” the report adds “high cholesterol in women is not a statistically significant risk factor for sudden cardiac death. On the other hand, smoking is one of the most important predictors of sudden cardiac death in women.” Which makes one wonder: why doesn’t the American Heart Association start a television campaign to try to persuade more women and girls to stop smoking? Finally, despite widespread skepticism about statins and cholesterol, don’t expect the controversy to end anytime soon. There is just too much money and too much political muscle supporting the theory that 18 million Americans should be on statins. Millions have been made not only selling statins, but also testing patients’ cholesterol levels on an annual basis. As “The Other Drug Wars” puts it, “the case of cholesterol illustrates well how the demands for testing and drugs interact: testing leads to increased utilization of cholesterol lowering drugs, which in turn leads to even more testing, which in turn leads to more drug utilization.” In 1999, the authors of “The other Drug Wars” were pessimistic that reason would ever trump hype. Quoting T.J. Moore’s book, Heart Failure, they noted that “The National Heart Lung, and Blood Institute’s eager partners in promoting cholesterol consciousness are the drug companies which are understandably very excited that the government is creating their largest new market in decades…A program that may have truly begun in sincere but somewhat misguided zeal for the public good, became very quickly intertwined with greed. The world was learning how much money could actually be made scaring people about cholesterol.” “Crowds of other agencies and companies have joined in the sustained reinforcement of the importance of cholesterol through the advertisement of their respective products,” the authors of “The Other Drugs Wars” continued. “One can hardly open a magazine or browse the internet without seeing offerings of the latest anti-cholesterol miracle drug, new low-cholesterol wonder diet, new life-saving cholesterol treating device or health-conscious cholesterol-lowering food product. “The voice of evidence questioning the value of directing so many public resources towards cholesterol control was and is still being lost amongst the thousands of advertising messages directed at the public.” Perhaps the time has come for “the voice of evidence” to make itself heard. It’s not just that money is being wasted –or that close to half of the 18 million Americans taking statins may not benefit. All of them are being exposed to risks which range from serious muscle pain to memory loss that can look like Alzheimer’s. And too often, well-meaning physicians who have been sold on statins ignore their complaints. Posted by Maggie Mahar on February 29, 2008 | Email this post TrackBackTrackBack URL for this entry:http://www.typepad.com/t/trackback/856730/26643826Listed below are links to weblogs that reference The Origins of the Cholesterol Con, Part II:CommentsLT3Y--I hear you, and I appreciate the warning.But I spent eleven years writing investigative pieces for a financial magazine (Barron's) that actually moved the stock market.This meant that I had to have a pretty good sense of when someone is trying to lie to me --or trying to "play" me. This site doesn't attract many trolls. And when someone does come on who isn't helpful, I find that other commenters just don't respond. Posted by: maggie mahar | March 02, 2008 at 05:52 PM LT3Y--I hear you, and I appreciate the warning.But I spent eleven years writing investigative pieces for a financial magazine (Barron's) that actually moved the stock market.This meant that I had to have a pretty good sense of when someone is trying to lie to me --or trying to "play" me. This site doesn't attract many trolls. And when someone does come on who isn't helpful, I find that other commenters just don't respond. Posted by: maggie mahar | March 02, 2008 at 05:52 PM Heart Attack Story--I know. I completely udnerstand why people would be afraid to stop taking statins--even if they are not in the smaller group that we now think can be helped. (People under 65 who have had a heart attack or suffer from diabetes)Note-- this is what we Now think. This isn't carved in stone. Medicine is an evolving science. This could change, in either direction, in the future.. If I were one of those people, I woudl try to do a little online reserach to find out if there are doctors in my area who area little more sketpical about statins (i.e. realize they are not for everyone), and then seek a second opinion. Posted by: maggie mahar | March 02, 2008 at 05:42 PM I fall into the male, under 65, who has had a heart attack. I take a low dose daily statin so in theory the advatages outweigh the risks. However if I was outside that group and and taking statins I think I would be frightened to stop taking them, as the subliminal message is that if I stop, it will only be a short time until I have another heart attack!Posted by: Heart Attack Story | March 02, 2008 at 03:04 PM Maggie,I hate to be so picky, but Dr. Abramson's first name is John, not Jon.One thing to keep in mind is that there were no randomized placebo-controlled clinical endpoints trials of statins in people with heterozygous familial hypercholesterolemia (heFH). People with heFH usually have LDL levels in the mid-200s or above. When statins became available, it was considered unethical to put someone with LDL that high on a placebo. (There were some surrogate endpoints trials comparing low-dose statins with high-dose statins in heFH patients.)However, it is my impression that Dr. Abramson would support treating a least some people with heFH with a statin even if that person did not have heart disease or diabetes. I base this on the question & answer part of his website, which I looked at last year. Someone with heFH who was on a statin asked Dr. Abramson if he should stay on it. Dr. Abramson said that although there were no studies to answer the question, he guessed that the drug was helping prevent the person from developing heart disease (or words to that effect; I'm paraphrasing). I do not know Dr. Abramson, but since you do, you could ask him about this if you want. Also, I may be getting myself in trouble with Merrill, Bonnie, Mike and the other good people at CSPI, but I want to comment on an article in the latest issue of Nutrition Action Healthletter. (At the risk of embarrassing my teenage daughter, I just want to disclose that she goes to school with Bonnie's daughter and Mike's daughter.) The article is entitled "Cardio Quiz: Use Your Head to Protect Your Heart" (March 2008). The first sentence of the article states: "By the age of 40, your odds of having coronary heart disease are one out of three if you're a woman and one out of two if you're a man." I think what they meant to say is the following, which I got off the AHA website: "The lifetime risk of developing CHD after age 40 is 49% for men and 32% for women." I note that I have not tried to confirm whether the latter statement is accurate or not.The second thing I want to comment on relates to the discussion on page 11 on foods fortified with plant sterols. The article talks about how you can lower your LDL through consuming these foods, which include Minute Maid HeartWise Orange Juice, Benecol margarine, and so forth. As you can tell by the use of the word "HeartWise" in the name of the Minute Maid orange juice, foods with added plant sterols or stanols are allowed to advertise themselves as "heart healthy" or whatever. The problem with this from my point of view is that this claim was approved solely based on the fact that plant sterols and stanols lower LDL. No studies have been done that show that plant sterols and plant stanols lower the risk of heart attacks and strokes. (It seems unlikely that any such studies will ever be done.) For all we know, consuming these fortified foods may *cause* heart disease (or other bad effects). One reason for caution is that it is known that very high levels of plant sterols are harmful. We know this because there is a rare genetic disease called sitosterolemia in which plant sterols accumulate in the blood. This disease causes tendon xanthomas, arthritis and heart disease. It could be that the stuff is perfectly safe at the levels you would get from eating these fortified foods, but we just don't know one way or the other.I realize Nutrition Action did not actually say that lowering your LDL by eating foods fortified with plant sterols is going to help prevent you from having a heart attack, but that's the message that people are going to take away. Given that the CSPI crowd tends to be highly skeptical of unsupported advertising claims, the article (or that part of it) just surprised me a little. Posted by: Marilyn Mann | March 02, 2008 at 07:25 AM With respect to the proposed clinical trial of aspirin versus a statin, are you suggesting a trial in people without coronary heart disease? Would this be a trial with clinical endpoints?Posted by: Marilyn Mann | March 02, 2008 at 03:42 AM You mean Vytorin, which is a combination of simvastatin and ezetimibe. Actually, it was already known before the ENHANCE results were announced that ezetimibe did not have the same pleiotropic effects as statins. Landmesser, et al, Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans, Circulation. 2005;111:2356-2363. In this study, simvastatin improved endothelial function and ezetimibe did not. Fichtischerer et al., Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for "pleiotropic" functions of statin therapy, European Heart Journal (2006) 27, 1182-1190. In patients with stable coronary artery disease, neither ezetimibe nor ezetimibe combined with simvastatin improved endothelial function, while atorvastatin did improve endothelial function. There is no reason to think that elderly patients with heart disease benefit less from statins than younger patients with heart disease. Can you name the researchers who believe *all* of the benefits of statins are unrelated to LDL-lowering? I want to look at their research. Posted by: Marilyn Mann | March 01, 2008 at 08:23 PM Brad--I completely agree that statins do offer a real benfit for a signifcant group of patients.I tried to make that clear when quoting Harvard's Abramson in my first Cholesterol post (scroll down to part I, a week ago) saying thst statins do indeed offer real benfits (which in most cases, outweigh risks) for people, "under the age of 65, who already have had a heart attack or suffer from diabetes."Others question whether women in this group enjoy bnefits that outweigh risks . . . but I decided to go with the broader definition of who benefits -- while including the concerns about women.Bottom line: Given that statins are the most popular drug in his country, we just don't know nearly as much as we should about exactly who they help--and the risks. Thanks for your comment--Maggie Posted by: maggie mahar | March 01, 2008 at 06:45 PM Marilyn--Thanks for picking up on the typo. I'll have "Ernrigchanged to "Enig." She is very good---and deserves to have her name spelled right! Posted by: maggie mahar | March 01, 2008 at 06:25 PM Marilyn--Thanks for picking up on the typo. I'll have "Ernrigchanged to "Enig." She is very good---and deserves to have her name spelled right! Posted by: maggie mahar | March 01, 2008 at 06:01 PM Marilyn--The other component of Vytia IS a statin. The point is that by by putting two cholesterol-lowering drugs together (one a statin, one not a statin) Merck/Schering expected to see increased health benefits.After sitting on the results for a long time (and being threatened by a Congressional investigation) the companies had to admit that the trial showed no health benefits from the double-barreled cholesterol busters.The less expensive Statin half of the combination was just as successful on its own.This has led researchers to suspect that perhaps, while statins do help some people, they do it, not by lowering "bad" cholesterol, but in some other way. It appears that statins reduce inflammation--just as aspirin does. (And aspirin has helped many cardiac patients.)This would help explain why large populations in some countires with high "bad cholesterol" have low levels of heart disease, while others, in areas with low "bad" cholesterol have high levels of fatal heart disease.With questions surrounding the mortality benefits of statins and the importance of lowering LDL ("bad") cholesterol being asked in the media, some high-profile cardiologists have spoken out.In the January 29, 2008 issue of Circulation, with Drs H Robert Superko (St Joseph's Translational Research Institute, Atlanta, GA) and Spencer King III (Emory University School of Medicine, Atlanta, GA) debating the effectiveness of lowering LDL to reduce cardiovascular risk and suggesting that new strategies are necessary. . . "According to Superko and King, a danger for the future health of patients lies in assumptions that cholesterol reduction alone can stem the tide of coronary heart disease. They argue that "this is not enough" and state that the "well-meaning focus on LDL-cholesterol reduction has deflected interest in other therapeutic aspects of lipoprotein treatment that provide equal or greater benefit."According to Superko and King, a danger for the future health of patients lies in assumptions that cholesterol reduction alone can stem the tide of coronary heart disease. They argue that "this is not enough" and state that the "well-meaning focus on LDL-cholesterol reduction has deflected interest in other therapeutic aspects of lipoprotein treatment that provide equal or greater benefit.".Posted by: maggie mahar | March 01, 2008 at 05:59 PM I think you mean Mary Enig.Posted by: Marilyn | March 01, 2008 at 03:14 PM I believe the benefits of aspirin for preventing strokes and heart attacks are thought to relate to its anti-platelet effects.I just want to clarify that ezetimibe (Zetia, a component of Vytorin) is not a statin. It is a cholesterol absorption inhibitor. The ENHANCE results don't tell us anything about the benefits of statins, as the two groups of patients were on the same dose of simvastatin. The difference between the two groups was that one was also on ezetimibe. The fact that an intervention that lowers LDL may not be beneficial is not a new idea. In my view, if the FDA is going to approve drugs based solely on LDL-lowering, it should require the drug company to conduct a clinical trial with clinical endpoints as soon as possible after approval. By clinical endpoints, I mean heart attacks, strokes and deaths. The problem with ezetimibe is that it has never been shown to prevent heart attacks and strokes. There are three ongoing trials testing this but the results will not be out for a few more years.If anyone is interested in reading more about the pleiotropic effects of statins, a good source is the following: Wang et al, Pleiotropic effects of statin therapy: molecular mechanisms and clinical results, Trends in Molecular Medicine, Vol 14, Issue 1, Jan. 2008, 37-44.I'm not sure how we could know how much of the benefits of statins are due to cholesterol-lowering and how much are due to other effects. It seems unlikely, however, that none of the benefits of statins are related to cholesterol-lowering.There was an interesting study done by Helen Hobbs and colleagues related to people who have mutations that cause them to have lifelong low LDL levels. The researchers found that people with these mutations have much lower rates of heart disease than people without the mutation. The study was published in the New England Journal of Medicine in 2006. http://content.nejm.org/cgi/content/abstract/354/12/1264Similarly, people with mutations that cause lifelong elevated LDL (i.e., familial hypercholesterolemia) have much higher rates of heart disease than the general population. For example, my husband has this in his family, and his grandfather died of a heart attack at 35. His uncle died of a heart attack at 40.See the article by Brown and Goldstein for a succinct review of the evidence that LDL causes atherosclerosis (Koch's postulates for cholesterol Cell 1992 71: 187-188). Posted by: Marilyn Mann | March 01, 2008 at 09:37 AM Maggie,The primary endpoint you are discussing is cardiac related mortality. Also knowing statins have other potent anti inflammatory properties and salutary effects (as you point out), from a public health perspective, might it be better to discuss all cause mortality and QALY's as they relate to this class of medicine as well.While the "selling of statins" for one indication of use might be rooted in flawed science, and I think we all realize that that is egregious, the fact remains that this class of drugs still may favorably impact many patients. The crux is in whom, and at what cost. My sense is while they might be overused--but that is not proven, we should not throw the baby out with the bathwater. I would addend this point with you illuminating piece.Brad Posted by: Brad F | March 01, 2008 at 09:11 AM Perhaps I'm missing something about the idea of comparing aspirin (presumably low-dose) against statins. I've not seen anything to suggest low-dose aspirin is working as an anti-inflammatory, significantly blocking prostaglandin synthesis by inhibiting cyclo-oxygenases. My understanding was that the cardiac benefit was specific to aspirin, not other NSAIDs, by irreversibly acetylating the precursor to thromboxane B on platelets.On a quick search, I saw some arguments that the basic lipid-lowering effect of statins, HMG-CoA-reductase inhibition, may itself have a cardiac benefit. There were some nonspecific allusions that there might be a different anti-inflammatory effect involved.Can anyone point me in the direction of details on the latter? If the inflammatory substances in question are prostaglandins or leukotrienes, would not another NSAID be a better comparison than aspirin?Posted by: HCBerkowitz | February 29, 2008 at 08:56 PM Ryan, Merrill, Dr. Rick and TomThanks very much--and Ryan,thank you for picking up the typo! Tom, I'm on deadline right now and need to give your comment some thought, but I promise I'll get back to you soon-- mmPosted by: Maggie Mahar | February 29, 2008 at 02:13 PM "Why then, were we all so certain that HDL cholesterol led to fatal heart attacks?"I'm confused (or maybe I need to read more slowly), shouldn't that be LDL?Posted by: Ryan Stewart | February 29, 2008 at 11:28 AM Good job on this series (and thanks for mentioning the Center for Science in the Public Interest's work on this in 2004 in last week's post). Posted by: merrill | February 29, 2008 at 08:54 AM Maggie,I believe that you are referring to the ENHANCE trial. The only published data I have been able to track down is here: Am Heart J. 2005 Feb;149(2):234-9.I think that the results of that particular study were taken out of context. The subjects were people with familial hypercholesteremia. They started with cholesterols in the 300 mg/dl range, which were brought down by ~50%. While this seems like a large reduction, people seem to ignore that the absolute level of cholesterol is what has generally been pointed to as being important.It may very well be true that cholesterol has no, or little, effect on arthrosclerosis, but I'm not sure that the Zetia trial applies to the majority of the population or to how doctors treat high cholesterol. We do not aim for a % reduction, but rather for an absolute number (< 100 or < 70, depending on risk factors). So, reducing someone's cholesterol from 300 to 150 really doesn't address the issue if 150 is still unhealthy.I would, however, be interested in a head-to-head statin vs. aspirin =). Posted by: Tom | February 29, 2008 at 08:45 AM MaggieWHERE WERE THE DOCTORS?????Where they have always been because they are trained to do so- pushing pills! And "treating" lab results -NOT PATIENTSThe "pus" is at long last coming out!Thanks!Dr Rick Lippinhttp://medicalcrises.blogspot.com Posted by: Dr. Rick Lippin | February 29, 2008 at 07:16 AM Post a commentIf you have a TypeKey or TypePad account, please Sign In You are currently signed in as (nobody). Sign Out Name: Email Address: (Not displayed with comment.) URL: Remember personal info? Comments: Join the Email List and Receive Updates Your Email Address: Health Beat's Most ReadRecent PostsThe Origins of the Cholesterol Con, Part IIUpdate on FDA Stories: Business as UsualAs the Army Approaches a Breaking Point The Supreme Court’s Medical Device Decision Misses the PointThe Wall Street Journal Is Wrong on AvastinA Lesson in Health Care Innovation...from the Government?The Cholesterol Con--Where Were the Doctors? 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