Let’s Clear Up the Cholesterol Confusion

Every time I hold one of my subscriber seminars, the subject of cholesterol comes up—usually more than once. Obviously, it’s a source of great interest to many of you, as well as a source of ongoing confusion. The confusing part is this: you get one message from me and another from the media and your doctor.

One subscriber told me privately that he showed a recent newsletter article about cholesterol to his car­diologist. After reading it, the doctor said I was nuts and that I didn’t know what I was talking about—and that the research has overwhelmingly shown high cholesterol to be a major risk factor for cardio­vascular disease.

For years, I’ve been writing about how I no longer buy into the cholesterol-lowering frenzy that has turned the medical profession into a big vending machine for statin makers. Statins, as you know, are the drugs that lower cholesterol. Most doctors will recommend, and even nag, that you take them if your cholesterol numbers are high. And they will do so regardless of your age, gender, or whether you have evidence of arterial disease. In their minds, heart disease is prevented by lowering cholesterol.

A long time ago, I used to believe that, too. It made sense based on the research. Back then, I believed it to the extent that I even lectured on behalf of drug makers like Merck and Pfizer. I was a “cholesterol choirboy”—singing a refrain that made high choles­terol out to be the big, bad villain of heart disease.

Cracks in the Cholesterol Story

My thinking changed when I began to see con­flicting results among my own patients and in the medical research. For instance, I saw many patients develop heart disease even though they had low total cholesterol—as low, in fact, as 130!

These patients were telling me something different than the establishment message—that heart dis­ease wasn’t a simple cholesterol story. Other expe­riences reinforced my observations. In those days, we pushed people to undergo angiograms (invasive arterial catheterization imaging) if they had suffi­cient chest pain, borderline results on exercise tests, or cholesterol levels greater than 280. We did this because we believed that people with high cholester­ol were in danger of having a heart attack, and we wanted to see how bad their arteries were. Indeed, many times the arteries were diseased. But often, though, the arteries were healthy.

I soon found other doctors who had made similar dis­coveries, and I heard how study findings were being manipulated. Retired Vanderbilt University biochem­ist George Mann—who helped develop the world-famous Framingham heart disease study that raised interest in cholesterol—later described the cholester­ol hypothesis as “the greatest scam ever perpetrated on the American public.”

However, his and other dissenting voices have been drowned out by the “cholesterol chorus.” To this day, practically all of what has been published about cholesterol—and received media attention—supports the current cholesterol paradigm. Worse, it appears to have the backing of the pharmaceutical and low-fat food industries, as well as leading regu­latory agencies and medical organizations.

By contrast, you don’t read much about a population study that showed how the French have the highest total cholesterol levels in Europe—about 250—but the lowest incidence of heart disease. Or how a 10-year study on the Greek island of Crete failed to record a single heart attack despite its participants having an average total cholesterol of well over 200. Then there’s the statistic I often cite in this newsletter—that half of all heart attacks occur in people with “normal” total cholesterol. This fact was reported without much fanfare in an eye-open­ing 1996 article by Dr. William Castelli, who was director of the Framingham study research group at the time.

A New Way of Thinking about Cholesterol

Though you wouldn’t know it based on today’s obsession with cholesterol levels, cardiology has been slowly veering away from the narrow view of cholesterol as a primary cause of heart disease. Cardiologists are slowly accepting that it’s inflam­mation of arterial tissue that leads to heart dis­ease and most strokes. The field is realizing that although cholesterol plays a role in the biochemical process that creates damage in arterial walls—which in turn leads to plaque, occlusions, and clots—it’s a relatively minor one. In other words, they’ve realized that even though they may find cholesterol at the scene of the crime, it’s not neces­sarily the perpetrator.

Yet for most people, the word cholesterol remains synonymous with death and disease. In this coun­try, the pharmaceutical companies have even created a non-existent disease called hypercholes­terolemia, which simply means “high cholesterol.” I see the anxiety on patients’ faces when they come to my office and the first words out of their mouth are, “My cholesterol is high, and I’m really scared.” People are indeed worried if they have a total cho­lesterol score above 200.

I’m here to tell you, don’t worry. High cholesterol is not a death sentence. It’s a signal that you should have a more sophisticated blood test that will mea­sure the various subtypes of your LDL and HDL, and tell you whether your cholesterol warrants attention or is merely elevated. This type of informa­tion, which hasn’t been available until recently, can then help you make health and lifestyle choices that will have the best odds of improving your situation.

It’s Not How Much, It’s What Kind

The standard blood lipid tests that most doctors use to monitor cholesterol belong in the age of dino­saurs. Sure, they tell you how much LDL, HDL, triglycerides, and total cholesterol you have in your blood, but that’s about it.

About a year ago, I reported on the vertical auto profile, or VAP, test—the first of a new generation of lipid tests that break cholesterol down into fractions smaller than LDL and HDL and analyze the par­ticles comprising each of them. This was a notable advance because having a preponderance of certain types of particles can significantly raise your risk for heart disease. VAP allowed doctors to more accu­rately identify those people.

Recently, a second test has emerged, and it’s even a notch better. It’s called the Lipoprotein Particle Profile (LPP), and it’s offered by SpectraCell Labora­tories in Houston, Texas. The reasons I believe LPP has an advantage over VAP are because its meth­odology allows for more precise measurements, and because it can measure remnant lipoprotein (RLP). To date, no other test has been able to single out this important type of cholesterol, which I explain in more detail on the next page.

Don’t get me wrong—VAP still has a lot of value. In fact, I believe that both of these tests will not only change how we treat cholesterol, but how we talk about it. It’s common to hear generalizations such as “LDL is bad cholesterol, and HDL is good cho­lesterol.” But in reality, both LDL (low-density lipo­protein) and HDL (high-density lipoprotein) are far more complex. There are multiple subtypes of both, and some of those subtypes are good and some are bad. So, it’s not just about how high your LDL is. It’s about what kind of it you have, and how much. The same goes for HDL.

For instance, LDL particles can be large or small. It’s the small LDL particles that readily enter compromised arterial walls and fuel the inflam­matory process. Having a greater number of small LDL puts you at higher risk. Unfortunately, hered­ity plays a major role in how much small LDL you have, so you will be more limited in how you can address this situation if your level is high.

If you have significant numbers of small LDL—which you can find out by taking the LPP test—you need to be particularly mindful about exposure to things that damage your arterial walls and create opportunities for small LDL to affect them. These include cigarette smoke, mercury, lead, trans-fatty acids, insulin, and radiation (to name a few). You also need to closely monitor your homocysteine lev­els. Homocysteine is an amino acid that can cause your body to deposit sticky, artery-hardening plate­lets in blood vessels.

High levels of small LDL is of particular concern when the blood also contains a lot of Lipoprotein(a), or Lp(a)—the most dangerous of the blood lipids. Lp(a) is a specific type of small LDL particle, and it inflames the blood and makes it sticky—making it more prone to clotting. You want your level of Lp(a) to be as low as possible, ideally less than 30 mg/dL (standard and LPP tests), and 10 mg/dL (VAP test).

As I mentioned earlier, LPP is the first lipid test to accurately measure remnant lipoprotein, or RLP. To understand why RLP is so important, you have to remember how arterial plaque forms. When LDL cholesterol penetrates the endothelial wall to make repairs, it can become oxidized. Once oxidized, it stokes the inflammatory process that’s under way, calcifies, and eventually becomes part of plaque. RLP works the same way, except it doesn’t oxidize. It simply enters the endothelium and begins con­tributing to the inflammatory process.

Clearly, RLP is dangerous. But, until now, many lipid tests have not been able to single out RLP because they focus on particles that oxidize. Because RLP doesn’t do that, it has been over­looked. The LPP, however, can measure this inflam­matory factor—further improving your doctor’s ability to assess cardiovascular risk.

Another type of LDL particle is large and buoyant, and associated with lower disease risk. You want your LDL cholesterol to be of this type.

Different Profiles, Different Risks

In the context of LDL, it’s easy to see how advanced testing can be of great benefit. Two people with the same amount of LDL cholesterol may have widely different risk levels when it comes to cardiovascular disease. Should one of them have a preponderance of small LDL particles, he or she would be up to three times more likely to develop disease than someone who had mostly large, buoyant LDL.

Similarly, there are subgroups of HDL as well as significant differences in how efficiently they remove excess lipids. Just like LDL, not all HDL is created equal. You want to be high in the most functional HDL subgroup, HDL 2B.

“What about my total cholesterol?” you may be ask­ing. Well, it doesn’t mean much unless you have a level over 320 or so, at which point the risk of stroke increases. For those of you whose cholesterol is at or above that point, it behooves you to bring it down through lifestyle modification, including weight reduction and diet (eat a lot of fiber). I don’t recom­mend taking a statin unless you are a man with evi­dence of arterial disease. I’ve been very disappointed with the lack of results when I’ve used statins for women, and some research has linked the drugs with breast cancer in post-menopausal women.

What about your total LDL level, according to standard tests? If your doctor thinks it’s too high, suggest the advanced testing. In any case, I would be extremely reluctant to push an LDL level below 80, which some doctors recommend. It’s dangerous because of cholesterol’s essential functions in sup­porting cell health, hormone production, and brain function. Levels that are too low—even LDL—have been associated with cancer, aggression, cerebral hemorrhages, and amnesia. Low cholesterol may also affect your ability to combat infection.

What to Do If Your Doctor Prescribes a Statin…

Here’s what you have to remember if your standard cholesterol numbers are high and your doctor tells you to take a statin:

  • Ask your doctor to follow up with a VAP or LPP test that clarifies your individual cholesterol fractions. If your results show you have fractions that put you at risk for heart disease, a statin may be in order (see the following criteria).
  • If you’re a male up to age 75 and have coronary artery disease, and the advanced test shows you have predominantly small LDL, then it’s a good idea to go for the statin drug. Statins also have strong anti-inflammatory properties—and that’s actually the powerful effect you are looking for in this situation. Research has also shown that statins have the ability to reduce blood viscosity, which would also be of benefit to you. If you’re over age 75, I don’t recommend statins unless you have chest discomfort or shortness of breath. The drugs have too many downsides in this age group.
  • If you’re a woman and do not have unhealthy levels of inflammatory markers—including homocysteine, fibrinogen, and C-reactive pro­tein—I would pass on statins. However, if you have arterial disease and your cholesterol pro­file includes high levels of small LDL and other inflammatory markers, a statin may provide you benefit as an anti-inflammatory agent and as a means to reduce blood viscosity.

Finally, if you mention LPP or VAP to your doctor, don’t be surprised if they don’t know what you’re talking about. I recently taught a continuing educa­tion course on anti-aging cardiology to 150 conven­tional doctors and cardiologists. Most of them didn’t know these new lipid tests existed. Fortunately, as a subscriber to this newsletter, you do—and because of that, you have a leg up in understanding your true risk for heart disease.

How to Request an LPP Test

To have an LPP test, you must ask your doctor to request the collection kit from SpectraCell by calling 800-227-5227  or 800-227-5227. The blood draw may be done at your doctor’s office or at an approved lab. Test results will be sent directly to your physician.

For more information on both tests, which are cov­ered by Medicare and most insurance plans when ordered by a physician, visit their Web sites at www.thevaptest.com and www.spectracell.com.

References:

  • Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis. 1996;124:Suppl:S1–S9. Review.
  • Elias PK, et al. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosomatic Medicine. 2005;67(1):24–30.
  • Golomb BA. Implications of statin adverse effects in the elderly. Expert Opin Drug Saf. 2005;4(3):389–397.
  • Kawakami A, et al. Remnant lipoproteins and atherogenesis. Ann NY Acad Sci. 2001; 947(1):366–369.
  • Krumholz HM, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994;272(17):1335–1340.
  • Lamarche B, et al. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec cardiovascular study. Arterioscler. Thromb. Vasc. Bio. 1997;17(6):1098–1105.
  • Mauch DH, et al. CNS synaptogenesis promoted by glia-derived cholesterol. Sci­ence. 2001;294(5545):1354–1357.
  • McNamara JR, et al. Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study. Atherosclerosis. 2001;154:229–236.
  • Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–1630.

This article originally appeared in the August 2008 issue of Dr. Sinatra’s monthly written newsletter, Heart, Health & Nutrition. HMDI has reprinted this article with permission from Healthy Directions, LLC (© 2008 Healthy Directions, LLC).

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