Response by MRC to Dr. Gotto's Q and A session The Highs and Lows of Cholesterol Q. If you had to rate the importance of reducing risk factors for heart disease, where does lowering so-called bad cholesterol, or LDL, fit in? A. Lowering LDL is right up at the top of the list. The evidence of the benefits of LDL lowering is overwhelming. If you look at the demonstrated therapeutic benefits of the statins, whose primary effect is to lower LDL, RESPONSE: There is no doubt that Statins do reduce LDL. But I can find no evidence that reducing LDL is of any benefit to most people. they slow the progression of atherosclerosis, reduce major coronary events and reduce the need for surgical interventions like angioplasty. RESPONSE: I have never found any evidence that this statement is true for people who do not already have heart problems. In secondary prevention [in those who already have coronary heart disease], they also reduce the risk of stroke, dying from heart disease and overall mortality. RESPONSE: I have not seen any good evidence that this is true Even if it is true -- it would not be a good reason for the average person who does not have heart disease to take statins Q. Even before statins, people were advised to lower their LDL. Have the clinical studies on statins given credence to this approach? A. Yes, cardiologists were skeptical of the benefits of lowering cholesterol until the so-called 4S trial [Scandinavian Simvastatin Survival Study] came out in 1994, ... RESPONSE: This is simply not true and Dr. Gotto must know it is not true. The movement to lower cholesterol was prompted by the Framingham Study which started in 1955. See my report at ... which showed statins could increase life span in people with coronary heart disease. RESPONSE: Where is the evidence? Are we to simply take Dr. Gotto’s word? I do not believe what he says is true -- but even if that is true -- it would be no reason to give statins to people who do not have heart disease. That was a turning point. The fact of the matter is if we hadn’t had statins, we probably would never have been able to make such a convincing case and obtain such a consensus for the benefits for lowering LDL. RESPONSE: This is a typical technique. It simply take the previous statements as accepted proof and builds the argument on those bald statements that have no evidence. A consensus is not proof. Q. How much can diet lower LDL? A. Diet is very important. Usually most people can achieve a 5 to 10 percent decrease in LDL level with diet. If you can maintain the diet over a period of time, that’s very good. Also, if you’re taking statins and you’re not following a diet, you could partially undo the effects of statins. In Japan they’re able to get by with much lower doses of drugs largely because of their healthier diet. RESPONSE - We can accept that - but it has little to do with his main thrust of cholesterol being bad and causing heart didease Q. What is aggressive lipid lowering, and who requires it? A. Aggressive lipid lowering is bringing the LDL very low. It’s for people who are at high risk, meaning they already have coronary disease, and for those who are at very high risk, meaning they’ve already had an event and still have risk factors like diabetes or uncontrolled hypertension. The recommendations state that for people at high risk, their LDL should be under 100 [milligrams per deciliter], and for those at very high risk, they have the optional target of getting LDL under 70. RESPONSE: This does not tell us anything about cholesterol and heart didease Q. It that achievable? A. It is achievable, but it’s not easy for many people. It depends on what your LDL is to begin with. It requires a combination of nonpharmacologic measures, such as diet or exercise, along with one or more medications to lower the LDL. If you don’t reach your target on statins and diet, there are other drugs you can use on top of that. RESPONSE - Ho hum. Q. Why is it important to get LDL so low? A. There was a study called the Treating to New Targets, or T.N.T., trial, which showed that in people with coronary heart disease, lower is better. The study compared taking 80 millligrams of atorvastatin (Lipitor) versus 10 milligrams. The 10 milligram group achieved an average LDL of 101, whereas the 80 milligram group had an LDL of 77 and had a 22 percent greater reduction in cardiovascular events than the 10 milligram group. Patients down in the 70 range do better than those in the higher range. RESPONSE: There is not enough data here to make a judgment on the validity of his remarks. Note however that the study was made with people who already had heart disease -- it shows nothing about people who do not have heart disease. Q. A recent study found that women are much less likely than men to drive their cholesterol down to the recommended levels. What explains this? A. We haven’t been aggressive enough when treating women. We tend to think they’re not at risk of coronary disease. Another undertreated group is diabetics. They ought to start taking a statin at the same time as they’re given medications for diabetes. Cardiovascular disease is a major complication of diabetes. RESPONSE: More statements without evidence. It should be given little weight Q. Are there a lot of people who have borderline risk factors that should be treated but aren’t? A. Most people are asymptomatic. We could do a lot of good and prevent a lot of events if we started treatment early in life and treated borderline people, not just those with moderate to high risk. We could treat people with a 5 to 10 percent risk of having a heart attack in 10 years with diet and exercise primarily. In the 10 percent range, we’d treat with diet first, but if the response isn’t satisfactory, we add a statin. RESPONSE: Here he seems to be advocating the use of statins for almost everyone -- in spite of lots of evidence that reducing cholesterol is harmful A. Yes, you have to take it for two to three years before you see a maximum benefit. Once started, you should stay on it for the rest of your life. RESPONSE: What a great business. It is something that almost everyone should take forever. Q. But many people go off of statins? A. Yes, for a number of reasons. There’s a misconception -- some people think if you get your cholesterol down to normal, then you don’t have to take it anymore. That’s not true. Studies have shown that you’ll have the benefits for a period of time after stopping, but after a couple of years, you’ll lose them. RESPONSE: I have never seen good evidence that statins are good in the first place -- so this statement seems ridiculous. Q. Why does LDL go up for certain people, even if they’re following a very good diet? A. It goes up with age, due to a decrease in the body’s ability to clear cholesterol out of the blood. But for some people, their bodies are cranked up to make LDL, or they can’t remove it as efficiently as others, so they need the help of the drugs. The reason statins are so helpful is that even those who are trying their best to reach their target and still can’t do it have something else to rely on. RESPONSE: This does not say anything of importance if you do not accept his original unproven premise that cholesterol is bad. Q. Let’s turn to HDL, the “good” cholesterol that helps clear “bad” cholesterol out of blood vessels. Cardiologists had high expectations for the experimental drug torcetrapib, which raises HDL, but the study surprisingly found that people on the drug had higher rates of coronary events. A. We know that a low HDL is associated with an increase in risk. The question is, if you raise it, do you reduce the risk, and does it matter how you raise it? Obviously, it does. Raising it with torcetrapib, which increased HDL by 70 percent and also decreased LDL by 40 percent, caused an increase in deaths and more events. So we don’t know if the mechanism is flawed or if it was just that particular chemical entity, torcetrapib, that was flawed. There are other drugs in the class that are being tested, so the jury is out. The cardiology community is not nearly as enthusiastic now as it was before this trial came out. RESPONSE: His answer is sheer nonsense. Here is a drug that (a) increases HDL and (b) reduces LDL and (c) leads to an increase in death and he simply says “the jury is out” and “(we) are less enthusiastic”. Q. How are doctors treating low HDL now? A. Patients who have low HDL still benefit from statins, which raise HDL between 5 and 15 percent. Not much, but they’re still helpful, plus they get the benefits of a lower LDL. Niacin is the most effective drug we currently have, raising it 20 to 25 percent. It causes flushing, which is why it’s not more widely used. You can take an extended-release formula or take an aspirin an hour before taking niacin to reduce flushing. When you get the LDL down to 50 or 60, you probably have as close to as much benefit you’ll get from lowering LDL. At that point, you have to look at other mechanisms, such as raising HDL or reducing triglycerides. RESPONSE: But I have never seen tests that show LDL or HDL levels are related to heart disease in otherwise healthy people. Q. Is there a special diet for raising HDL? A. Well, we know a high-carbohydrate diet lowers HDL. Exercise is very important in raising HDL, in weight control and in lowering triglycerides. Exercise is more helpful in raising HDL than it is in lowering LDL. Q. What should people know about their own cholesterol? A. It’s important to know what your total cholesterol and LDL and HDL are, but also to know what your overall risk is, including your family history, smoking, blood pressure and diabetes, because your overall risk determines where your LDL should be and what treatment you might need. RESPONSE -- That, in my opinion, is pure guesswork. I have never seen any evidence that shows an existence of the relationships he claims are important. Martin R. Carbone -- 4/25/08 |