A Sea Change in Cholesterol Thinking

A Sea Change in Cholesterol Thinking
Surprising discovery dramatically ups the ante on the benefits of cholesterol lowering
By Will Block

hen’s the last time you ate just one handful of peanuts, or had just one bite of a chocolate bar? If a little is good, then more is better, right? Being only human, we tend to live by that precept, especially where scrumptious food is concerned. Yet we’re bombarded daily with admonitions to avoid overindulgence in many of the things we like best, because, we’re told, too much of a good thing can be a bad thing. (Mae West famously said, “Too much of a good thing can be wonderful,” but she wasn’t talking about food.)

So cutting back on the really good stuff has become one of the crosses we must bear in order to make it through life—to make it through a long and healthy life, to be more precise. We’ve become conditioned to feel guilty about eating too much food that’s rich in sugar, fat, or cholesterol, and we understand why excessive amounts of these nutrients are indeed unhealthy. Knowing what we do about what’s best for us, it behooves us all to make wise choices at the supermarket and in the kitchen.

Lower Cholesterol Levels Are Better for Everyone

By now, everyone who hasn’t been living on Mars knows that one of the things that are best for us is low cholesterol levels. If our levels are high—and they are borderline high or high in about half the adult population of the United States—we should darn well lower them if we want to reduce our chances of experiencing such life-altering (or life-ending) events as a heart attack or a stroke.* But that’s not all. In an article in last month’s issue of Life Enhancement (“Got Cholesterol? Lower It!”), we found out that, for patients with coronary heart disease, even if their cholesterol levels were already low, lowering them further would further reduce their risk.*

There is abundant clinical evidence that lowering cholesterol levels also substantially reduces the risk for cognitive impairment and dementia (see “Policosanol May Be Good for Your Brain as Well as Your Heart” in the June 2002 issue), and there is suggestive evidence from laboratory, animal, and clinical trials that cholesterol-lowering drugs may also reduce the risk for certain kinds of cancer.

The surprising conclusion from that large study was that it didn’t much matter where the patients started from in terms of cholesterol levels: the degree of risk reduction was about the same (and very significant) whether their levels were initially high or low!1 It turned out that cholesterol reduction was beneficial for everyone, regardless of their sex, age, disease status, or initial cholesterol levels. The authors described their evidence as “unequivocal”—a rarity in the complicated business of conducting and interpreting clinical trials.

So if you’ve been self-satisfied because your cholesterol levels are nice and low, here’s a wake-up call: you could have a lot to gain by lowering them even more, especially if you have cardiovascular disease or are at significant risk for it owing to other factors, such as hypertension, obesity, diabetes, or being a smoker.

A Big Deal Exciting Breakthrough Sea Change

Here’s another surprise—a major one, according to some experts: researchers have discovered that intensive, high-dosage therapy with cholesterol-lowering statin drugs produces much greater benefits in cardiac patients than the benefits achieved with standard, normal-dosage therapy.2 Not only does the higher dosage reduce cholesterol levels by much more than the standard dosage, but also, more significantly, it substantially reduces the patients’ risk for death or a major “cardiac event”—the kind of event no one ever wants to experience. The reason this came as such a surprise is because the study in question was actually designed to show that there would be no significant difference between the standard therapy and the intensive therapy.

Why the researchers believed that the intensive therapy would not be superior to the standard therapy (or, as they put it, that the standard therapy would not be inferior to the intensive therapy) is beyond the scope of this article. Suffice it to say that they had good reasons, but they were mistaken—very mistaken, as they were quick to admit. In response to the dramatic turn of events, various prominent cardiologists not connected with the study have been quoted in the press as saying, “This is really a big deal . . . it’s very exciting”; “It’s a breakthrough”; and “This is a sea change . . . this is big.”

Standard and Intensive Therapies Go Head-to-Head

Wow. That sounds . . . big! To see why, let’s put some numbers on it. First of all, the study encompassed 4162 adult patients (average age 58), of whom 22% were women, at 349 sites in eight countries. All had been hospitalized for an “acute coronary syndrome”—either a heart attack or an attack of high-risk unstable angina pectoris—within 10 days before being enrolled in the study (but enrollment was contingent on having been medically stabilized during that interval). Their median level of LDL-cholesterol—“bad cholesterol,” the kind that needs aggressive reduction—was 106 mg/dL (milligrams per deciliter). Current medical guidelines call for LDL levels to be less than 100 mg/dL for patients with heart disease or diabetes, but that figure is likely to be revised downward soon as a result of this and other recent studies.

On a randomized, double-blind basis, half the patients were given standard cholesterol-lowering therapy: 40 mg/day of pravastatin (Pravachol®), a statin drug. The other half were given intensive cholesterol-lowering therapy: 80 mg/day of another statin drug, atorvastatin (Lipitor®).* The patients’ cholesterol levels and state of cardiovascular health were then monitored for 18 to 36 months (average 24 months).

*Why not use the same drug at different dosages? The authors did not explain why, and they admitted that the results of their study might be due in part to differences between the two statins rather than to the difference between the two dosages. Further studies using different dosages of the same drug should resolve this question.

Intensive Therapy Greatly Improved Patients’ Prospects

Within 1 month, the patients’ LDL-cholesterol levels dropped sharply—but by very different amounts—and then leveled off. The standard therapy produced a median value of 95 mg/dL (a 10% drop), whereas the intensive therapy pushed the median value down to 62 mg/dL (a 42% drop). That’s impressive, but what really got the researchers’ attention was the dramatic improvement in the patients’ long-term prospects for staying alive and healthy as a result of the intensive therapy.

By comparison with the standard therapy (which is itself very effective in reducing risk factors), the intensive-therapy patients’ risk for heart attack was reduced by 13%; for revascularization (a surgical procedure such as angioplasty or coronary artery bypass), by 14%; for unstable angina requiring hospitalization, by 29%; for death from coronary heart disease, by 30%, and for death from any cause, by 28%. The overall risk for death from any cause or a major cardiac event was reduced by 16%. The only major event for which there was no risk reduction (with either therapy) was stroke.

Overall, the benefits of the intensive therapy were strikingly consistent in both men and women; in old and young; in patients whose hospitalization had been for heart attack or for unstable angina; in patients whose cholesterol levels had been high or low; in patients who had or had not previously taken statin drugs; in patients with or without diabetes; and in patients who had or had not previously been smokers.

Although both drug regimens were generally well tolerated, there were three times more liver-related side effects (3.3% vs. 1.1%) with the intensive treatment than with the standard treatment. (There were no cases of rhabdomyolysis, a serious muscle disease that has been linked mainly with certain other statin drugs.)

Upping the Ante on Cholesterol Lowering

In response to these startling results, cardiologists are talking about revamping their approach to cholesterol therapy by becoming much more ambitious than in the past, with new, lower target levels not just for cardiac patients, but for all adults, regardless of their current state of health. More and more doctors are coming to the conclusion that aggressive cholesterol lowering is so important for everyone’s health and longevity that it should become a major focus of health care worldwide. In other words, they believe that, where cholesterol lowering is concerned, more is better. (Be careful, however, in applying this principle. See the sidebar, “Is More Always Better?” And for the financial implications, see “Statins = Big Bucks.”)

Is More Always Better?

In prescribing drugs—or in recommending supplements—doctors are guided by the results of clinical trials that seek to establish a dose-response relationship for the substance in question, i.e., the relationship between the amount of the substance administered and the pharmacological benefit observed. Sometimes (but often not) nature is considerate and demonstrates a simple, clear dose-dependent relationship, in which the more you take, the greater the benefit—up to a point. The key questions then are: Where is that point, and how reliable and reproducible is it? And is the substance still safe to take at this level?

Let’s say that the point of maximum efficacy has been established, and the observed benefit apparently levels off thereafter. Taking more than the amount required to reach that maximum would just be a waste of money. Often the perceived benefit doesn’t just level off, however; instead, it starts to decline (for reasons that may or may not be understood). Thus there is a peak in the dose-response curve, and the goal of the researchers is to find that peak and verify its validity so that doctors can prescribe accordingly.

In either case—whether the dose-response curve has leveled off or is declining—it’s important not to exceed the optimal dosage. It’s not just so as to avoid wasting money (in the first case) or to avoid a diminished benefit (in the second case), but also to avoid something more sinister: the possibility of adverse effects. If the dosage becomes too high, the action of the drug or supplement may reverse itself and start having the opposite effect (again, for reasons that may or may not be understood). Or it may start exerting harmful effects unrelated to the health problem for which it was intended.

In short, the drug or supplement could become a toxin rather than a remedy. That is why it’s so important that recommended dosages be based on hard scientific evidence of safety as well as efficacy, and that consumers follow the directions, resisting the natural human impulse to think that “more is better.”

Statins = Big Bucks
Statin drugs are expensive! A starting dosage (10 mg) of Lipitor costs about $900 per year, and the 80-mg dosage used in the recent study costs about $1400 per year. Statins are already costing American consumers $12.5 billion annually—more than any other type of prescription drug—and the prospects for that figure to skyrocket have now increased dramatically.1

About 64 million Americans have some form of cardiovascular disease, and 1.4 million die from it each year. Under the current, modest guidelines for acceptable cholesterol levels, it is estimated that 36 million Americans should be taking cholesterol-lowering medications, but only 11 million of them actually are. Worldwide, about 200 million people could benefit from these medications, but only 25 million are getting them.1

Under the new way of thinking, however, virtually all adults—at least in cholesterol-rich societies such as ours—should be taking cholesterol-lowering medications, and many of them should be taking much more than they are now. Where statin drugs are concerned, the financial implications are staggering. How fortunate that a much more economical alternative—policosanol—is available.

  1. Topol EJ. Intensive statin therapy—a sea change in cardiovascular prevention. New Engl J Med 2004;350:1562-4.

In the study authors’ words:2

Although prior placebo-controlled studies have shown that a standard-dose statin is beneficial, we demonstrated that more intensive lipid lowering significantly increased this clinical benefit. . . . we also observed a continued benefit of atorvastatin therapy throughout the follow-up period of two and one-half years. . . . our findings suggest that patients with acute coronary syndromes who receive early and intensive lipid-lowering therapy continue to derive benefit in the chronic phase of atherosclerosis when high-dose statin therapy is maintained.
In an accompanying editorial, Dr. Eric J. Topol, another authority on the subject, wrote:3
Previously, it was considered optimal to lower the LDL-cholesterol level to less than 100 mg/dL. That axiom has now come under serious question, because we know that atherosclerotic progression and clinical outcomes will be ameliorated by much more aggressive use of statins. . . . The implications of this turning point—that is, of the new era of intensive statin therapy—are profound. . . . There will soon be a sea change in the prevention and management of atherosclerotic vascular disease.

Policosanol Rivals Statins in Efficacy

As was mentioned in last month’s article, the costly statin drugs, for all their effectiveness in reducing cholesterol levels, have a serious rival from the supplements arena. A very safe and effective (and far more economical) natural alternative is the sugar-cane extract policosanol, which has been found in numerous studies to rival—and sometimes exceed—the statins in its ability to reduce total cholesterol and LDL-cholesterol levels (as well as triglycerides) while substantially increasing levels of HDL-cholesterol (“good cholesterol”).* These studies have shown that the optimal amount of policosanol is 20 mg/day and that this amount is extremely safe to use, with virtually no adverse effects. (Policosanol is not a sugar, by the way, and has no effect on blood sugar levels.)

*Some recent Life Enhancement articles on policosanol’s role in heart health include: “Policosanol—Nature’s Remedy for High Cholesterol” (February 2002), “Policosanol—A Better Alternative to Statin Drugs” (May 2002), “Policosanol Improves Every Measure of Blood Cholesterol” (October 2002), “Policosanol Keeps Your Arteries Healthy” (November 2002), “Policosanol Improves Cardiovascular Health” (December 2002), “Our Cholesterol Levels Are Still Too High” (October 2003), and “Got Cholesterol? Lower It!” (May 2004).

Whether you’re a cardiac patient or are at risk for becoming one—and even if you’re not at appreciable risk, as far as you know—it’s becoming quite clear that one of the best things you can do for your health and longevity is to lower your cholesterol levels aggressively, regardless of where they are now. Think of it as a lifestyle choice, with the emphasis on life.


  1. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6;360:7-22.
  2. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM, for the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. New Engl J Med 2004;350:1495-1504.
  3. Topol EJ. Intensive statin therapy—a sea change in cardiovascular prevention. New Engl J Med 2004;350:1562-4.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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