Cholesterol Management 101

An Analysis of the Scientific Statement from the American Heart Association

Cardiovascular disease is the leading killer of men and women in the US. Despite the fact that over 150 million lipid panels are done annually, the prevalence of cardiovascular disease continues to grow in this country.

Last week in the online version of Circulation, the Journal of The American Heart Association, a scientific statement about triglycerides and cardiovascular disease was released. This document, to be published in the journal form on May 24, 2011, was the result of two National Institutes of Health evidence-based consensus conferences that evaluated the role of triglycerides in cardiovascular risk assessment and provided recommendations for treatment in those individuals with high triglycerides. (more…)

Is it necessary to not eat 8-12 hours before one has their blood drawn to check cholesterol levels or is it okay to draw it after eating? I am asked this question from patients almost on a daily basis. The brief answer is yes. Let me explain why. (more…)

In 2007, I started a series about the safety of statin therapy that I wrote for my Cholesterol Management 101 Blog on WebMD. One of the topics I discussed with respect to this class of drugs was on the potential effects on the liver. As I stated in that post, all the information was current and evidence-based at that time.  It was provided by the National Lipid Association Statin Safety Task Force, which was an independent body of experts whose sole task was to answer certain question using all available resources and literature available. Their conclusions were published in the American Journal of Cardiology. Since that time, the GREACE Study-liver function test data was published in The Lancet in November 2010. It further confirms that the myth of statin induced liver toxicity is just that — a myth. (more…)

I want to digress a little from talking about cholesterol, so that we can talk about the use of aspirin for prevention of heart attacks, strokes, and other blood clotting problems.  Aspirin is commonly used for minor aches and pains and to reduce fever. (more…)

Ten Things Your Physician Probably Doesn’t Know About Cholesterol – Part Five

Photo: Pascal Broze

Omega-3 fatty acid, also known as fish oil, is primarily used to lower one’s triglycerides, not to lower one’s bad cholesterol.

The American Heart Association has suggested different levels of omega-3 fatty acid (O3FA) intake depending on one’s health status. For patients without coronary artery disease (CAD), eating a variety of fish (preferably fatty) at least twice a week is recommended. Fish oil supplements are recommended for patients with CAD, and high dose O3FA (about 4000 mg/day) is recommended for patients with high triglycerides.

Early studies demonstrated that the major effect of O3FA is to lower triglyceride levels between 10-45% depending on the severity of the triglyceride level and the dose of O3FA used. At the same time there is also a tendency for the LDL (bad cholesterol) to rise up to 30%, for LDL particle size to enlarge, and for HDL (good cholesterol) to increase up to 7%.

Until the availability of a prescription O3FA (sold under the name Lovaza, containing 840 mg of EPA and DHA (the two main O3FAs) and 60 mg of other O3FA in a 1000 mg tablet) in 2004, the treatment of high triglycerides with omega-3 fatty acids required the ingestion of large amounts of unconcentrated fish oil. Now that many insurance companies and Medicare drug plans pay for Lovaza, many Americans have begun to take fish oil. Most of these over-the-counter products were not regulated to control environmental contaminants such as heavy metals, pesticides, and dioxin. So unless it is a reputable manufacturer that has been researched thoroughly, I would be cautious about taking any over-the-counter remedy. All brands are not alike.

I think it is extremely important that patients look on the side of the bottle because most purchased O3FA says 1000 mg but may actually contain as little as 300 mg of EPA and DHA. Thus, one would have to take around 7 tablets if they are trying to take 2000 mg a day, and not just 2 of the 1000 mg capsules.

The most common complaint is an unpleasant fishy taste if one burps. Fish oils are naturally susceptible to oxidation accounting for their rancid conversion and patient intolerance. One of the most common ways to maintain shelf life, freshness, and reduce oxidation is to add vitamin E to supplements. I generally tell my patients to take their fish oil at night to reduce the instance of this problem.

Another practical way to improve tolerance and reduce the fishy aftertaste of the liquid O3FA is to refrigerate the container once opened. If one is taking the capsules, refrigeration before use will reduce the fishy taste. The manufacturing process is the most important measure to reduce the aftertaste and remove contaminants. It could be argued that when a patient describes a rancid taste that the product was poorly purified by the manufacturer.

Read the Series:

• 10 Things Your Doctor Probably Doesn’t Know About Cholesterol
• What Your Doctor Probably Doesn’t Know About HDL
• What Your Doctor Doesn’t Know: The Difference Between a Sterol and a Stanol
• C-Reactive Protein and Your Risk of a Heart Attack

Ten Things Your Doctor Doesn’t Know About Cholesterol Part Four

Many patients have been asking me about getting a blood test called C-reactive protein(CRP). They have heard that reducing it lowers their chance of dying from cardiovascular disease. I really do wish this was the case, but unfortunately it is not the answer to curing cardiovascular disease.

Highly specific C-reactive protein (CRP) is an acute phase reactant with a short half-life of approximately 19 hours and is a marker for inflammation. More than 25 studies published during the last 10 years have provided strong evidence that C-reactive protein predicts cardiovascular risk in various scenarios, not only in initially healthy subjects, but also in those who manifest atherosclerosis. This blood protein, which only a short time ago was thought by many to be more important than cholesterol, is now regarded as just a risk factor for cardiovascular disease.

Despite multiple attempts to develop drugs to lower C-reactive protein, many experts now feel that it is time to abandon that search. There was a study with 35 co-authors who developed a technique that allows one to get answers quickly about causality. The study showed that in a population, there are people who just happen to produce more C-reactive protein throughout their lives and others who just happen to produce less. If indeed C-reactive protein causes heart disease, those who make more would have more heart disease. The study did not find this. There was absolutely no association between CRP and heart disease rate. So, in other words, the association between C-reactive protein and heart disease must reflect something else.

In summary, C-reactive protein is thus just a marker of inflammation and increased cardiovascular risk. There is no evidence that lowering it with medications lowers ones risk of having a heart attack or stroke.

Read the Series:

• 10 Things Your Doctor Probably Doesn’t Know About Cholesterol
• What Your Doctor Probably Doesn’t Know About HDL
• What Your Doctor Doesn’t Know: The Difference Between a Sterol and a Stanol
• C-Reactive Protein and Your Risk of a Heart Attack

Share your comments and ask questions on the Cholesterol Management Community.

Ten Things Your Doctor Doesn’t Know About Cholesterol Part Three

We hear in the news and in commercials that plant sterols are good for us and lower cholesterol levels. We are even fortifying certain foods and some baby aspirin with these phytosterols. Yet these phytosterols may be more atherogenic (have the ability to initiate or accelerate atherogenesis — formation of fat deposits on the inner lining of blood vessels) than cholesterol in certain groups of people.

Stanols on the other hand are good for everyone and do lower cholesterol levels.

I am perplexed that the majority of physicians that I have encountered do not know the difference between a sterol and a stanol. Let’s start with some definitions.

• Cholesterol is a sterol. A sterol is a steroid with an alcohol group attached to it.

• Stanols are saturated or reduced sterols that are similar to cholesterol, but have a methyl or an ethyl group attached to them. This difference minimizes stanol absorption in the intestines.

• Cholestanol is a stanol. Cholesterol can be broken down by the liver into cholestanol and thus is a by-product of cholesterol metabolism.

If sterols or stanols are esterified (combined with fatty acids), then they can be incorporated into margarine. We consume many sterols from plant sources (sitosterol, campesterol, and stigmasterol), shellfish (desmosterol and fucosterol) and animal sources (cholesterol). All of these sterols, with the exception of cholesterol, are collectively referred to as noncholesterol sterols. Collectively, these sterols can be called phytosterols. Sitosterol represents about 80% of all noncholesterol sterols in the diet and is the most well known noncholesterol sterol in the diet.

When fats (triglycerides) enter the intestine in our food, they are broken down into their basic building blocks. The main breakdown products are called fatty acids. These fatty acids and sterols from dietary sources are packaged into what is called a micelle. These micelles “ferry” these fatty acids and sterols to the intestinal lining (epithelium). They are then absorbed by passive diffusion into the intestinal cells. Passive diffusion is a biological principle that substances flow through a semi-permeable tissue from an area of higher concentration to an area of lesser concentration. There is no pump required to get them out of the intestine and ultimately into the bloodstream.

Most humans absorb about 50% of sterols in the intestines. However, there are some people who are what is termed” hyperabsorbers” (they absorb 60-80%) and some are “hypoabsorbers” (they absorb less than 50%).

What happens when the sterols (cholesterol and noncholesterol sterols) are absorbed at the intestinal epithelium (the tissue that covers the small and large intestine)?

There is no doubt that the noncholesterol sterols are effective in reducing cholesterol levels by blocking absorption from the intestine. Evolution has gone to great lengths to keep noncholesterol sterols out of the human body. Almost immediately after absorption, some of the cholesterol and virtually all of the noncholesterol sterols are pumped back into the intestinal lumen (cavity) via something called ATP binding cassette transporters, ABC G5/G8.

The ATP binding cassette half-transporters, G5 and G8, facilitate transport of sterols out of cells of both the intestine and liver into the intestinal lumen and into the bile. Any sterols that are not pumped back into the intestine become part of the contents of the intestinally produced chylomicron particle that transports lipids to the liver. Only about 50-55% of ingested cholesterol makes it into chylomicrons in order to be transported to the liver for processing. 70% of the cholesterol in the body is transported as an ester, not as free cholesterol;  this is called cholesterol ester. Any noncholesterol sterols that were not sent back to the intestine via ABCG5/G8 also become part of the chylomicron and thus gain entry into the bloodstream.

Noncholesterol sterols are not esterified as humans do not have the enzymes necessary for that. When these unesterified sterols get into an arterial wall, they are more atherogenic than cholesterol (an esterified sterol). This means they have a greater artery clogging potential than does cholesterol.

If one lacks these transporters (homozygote), all sterols are absorbed and none are pumped back out: this is a very rare homozygous condition leading to the disease called sitosterolemia or phytosterolemia. It is associated with severe atherosclerosis, as noncholesterol sterols (which cannot be esterified) are more atherogenic than cholesterol.

Heterozygotes, people who have some transporter function, eliminate some but not all of these phytosterols. Stanols do not require these transporters to get back into these intestines. This is the reason that they are safe and effective to reduce cholesterol. Stanols are commercially available in the supermarket in a product called Benecol.

We are now beginning to understand that not everyone has perfect functioning G5/G8 transporters and noncholesterol sterols get into some people, especially those with family history of CAD (coronary artery disease) and postmenopausal women. These sterols may contribute to their atherosclerosis.

Such patients have slightly elevated sitosterol and campesterol levels (nowhere near what the homozygous patients have). Clinicians have no way of knowing which of our patients may be over absorbing sterols without measuring sitosterol levels. This is not routinely done in clinical practice. Although sterols are artificially added to many foods and baby aspirin, it should be clear that in some people they may do more damage than does cholesterol.

Prior to the introduction of eztemibe (Zetia), there was no way to effectively block the absorption of cholesterol and noncholesterol sterols. I have posted previously on this blog about ezetimbe (Zetia).  Zetia typically reduces the absorption of all sterols by 50%. It is FDA approved to lower cholesterol and noncholesterol sterols (sitosterolemia). Since the majority of cholesterol is produced in the liver, Zetia does not have a great effect in lowering ingested cholesterol.

Statins are the first line therapy in treating high cholesterol. In was shown in a trial called the 4S trial that as a statin lowers cholesterol levels and block it’s production, intestinal absorption of cholesterol and noncholesterol sterols increases. Using Zetia would eliminate this problem.

In summary, noncholesterol sterols serve no physiologic function in man. All sterols are atherogenic if they accumulate in the arterial wall. Stanols are saturated sterols. They are not absorbed and can be used therapeutically to reduce cholesterol absorption from the intestine.

Read the Series:

• 10 Things Your Doctor Probably Doesn’t Know About Cholesterol
• What Your Doctor Probably Doesn’t Know About HDL
• What Your Doctor Doesn’t Know: The Difference Between a Sterol and a Stanol
• C-Reactive Protein and Your Risk of a Heart Attack

Have questions about sterols and stanols? Let’s talk on the Cholesterol Management Community.

10 Things Your Doctor Probably Doesn’t Know About Cholesterol Part Two

Last week I started a series about the 10 things that your doctor probably doesn’t understand about cholesterol. The first point I talked about is the mystique surrounding the total cholesterol number of 200. I think point number two is probably the most misunderstood fact surrounding the treatment of high cholesterol. I hear every single day from family, friends and other doctors that they are in great shape because their HDL cholesterol (the good cholesterol) is high and that is the most important number to look at in a lipid panel. Well, guess what, everyone? Unfortunately, many of you are quite wrong, and I will explain why.

We know that low HDL cholesterol (good cholesterol) is a major risk factor for cardiovascular morbidity and mortality. It is included in the most well-known risk factor scoring system for cardiovascular disease called the Framingham scoring. Surprisingly, there is little clinical evidence that therapies directed at raising HDL cholesterol reduce risk. I will say that again, there is little evidence that raising one’s good cholesterol number protects them from having a heart attack, a stroke, or dying.

For this reason, the National Cholesterol Education Panel (NCEP) does not specify a number that would be the “optimal” HDL level of therapy. NCEP also states that raising one’s HDL is not a primary or secondary goal of therapy in order to reduce cardiovascular events or death. NCEP ATP-III statements about low HDL cholesterol were published in the journal Circulation in 2002. Here is a selection of facts from the article:

• A categorical low HDL-C should be defined as a level of  less than 40 mg/dL, in both men and women.
• Whether raising HDL per se will reduce risk for CHD has not been resolved. (Still true in 2010.)
• Some persons with severe deficiency of HDL do not manifest premature coronary heart disease; this suggests that HDL is not uniquely involved in atherogenesis (clogging of the arteries), as is LDL cholesterol (the bad cholesterol).
• A specific HDL cholesterol goal level to reach with HDL raising therapy is not identified.

In summary, when we measure HDL cholesterol, we are just measuring a number that tells us nothing about how well it functions. There is no way yet to measure how well one’s HDL functions, and thus, if one’s level is within normal limits, does the person with a higher HDL number have fewer events than a person with lower HDL number? This has never shown to be true in any randomized prospective human studies. This is also defined in scientific terms as no Level 1 evidence. There is only data in retrospective and epidemiological studies that show that the higher the HDL cholesterol number the lower the cardiovascular event rate.

I will put another twist in the HDL discussion. There is a level at which the HDL cholesterol in some people may be too high and dysfunctional, and actually be harmful to the arteries. There is another group of people whose HDL is called ApoA1 Milano, who are all originally from Limone, Italy, and have very low levels of HDL cholesterol. Approximately 3.5 percent of these people have HDL levels below 10mg/dl and have virtually no evidence of cardiovascular disease whatsoever. This is a kind of “super HDL.”

The bottom line is that in most people, low HDL cholesterol is bad and is a major risk factor for cardiovascular disease, but a high level may not be protective. The name of the game is to get the LDL cholesterol (the bad cholesterol) down. If anybody is really curious about this point, they can take a look at the Heart and Estrogen Replacement Study. In this study, 20 percent of the women who had heart attacks had HDL cholesterol levels in the 60-80 mg/dl range, which is well above normal.

Read the Series:

• 10 Things Your Doctor Probably Doesn’t Know About Cholesterol
• What Your Doctor Probably Doesn’t Know About HDL
• What Your Doctor Doesn’t Know: The Difference Between a Sterol and a Stanol
• C-Reactive Protein and Your Risk of a Heart Attack

Did you know that raising your HDL number doesn’t lower your heart risk? Post your comments on the Cholesterol Management Community.

Recently, after I was asked by a physician friend of mine a very simplistic question about cholesterol, I began to think about how many doctors are uninformed about the basics. I came up with 10 important points that  doctors, and many patients, should know about cholesterol. These 10 facts are not my personal opinions — they can be found in guidelines, textbooks, or published papers in one of the top peer-reviewed journals.

Traditionally, physicians looked at the total cholesterol and have told patients that if it is greater than 200mg/dl, it is bad and less than 200mg/dl, it is good. They have mistakenly believed that the total cholesterol number is the goal of therapy. Thus, it has become pretty much dogma that patients memorize their total cholesterol number so they can compare it with friends or tell their doctor.

Surprisingly, lowering one’s total cholesterol is not even mentioned by the National Cholesterol Education Panel (NCEP) ATP III as a goal of cholesterol management. The National Heart, Lung, and Blood Institute (NHLBI) launched the National Cholesterol Education Program (NCEP) in November 1985. The goal of the NCEP is to reduce illness and death from coronary heart disease (CHD) in the United States by reducing the percent of Americans with high blood cholesterol. In 1988, the first guidelines from the first Adult Treatment Panel of NCEP, which was called NCEP ATP I, were published. Since that time, many studies were published and guidelines have been updated. ATP II was published in 1993, and ATP III issued an evidence-based set of guidelines on cholesterol management in 2001.

Since this publication, five major clinical trials of statin therapy were published and addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. Thus, in 2004, an ATP III addendum was published with revised guidelines. These guidelines are currently used by physicians to treat high cholesterol levels. The next set of guidelines, called ATP IV, are scheduled to be published in the fall of 2011. Although physicians still talk about total cholesterol levels, all the ATPs have lowering LDL cholesterol (the bad cholesterol) as the primary target of therapy and have never once mentioned total cholesterol!

The truth is that prior to ATP I, based on the data from the famous MRFIT trial, it was shown that those patients with a total cholesterol greater than 200mg/dl were at increased risk of a cardiovascular event and those with a level less than 200mg/dl at a lower risk. Apparently, in the evolution of understanding lipid management and therapy, it was incorrectly stated that a magic cholesterol level of 200mg/dl or less was the goal of therapy.

Read the Series:

• 10 Things Your Doctor Probably Doesn’t Know About Cholesterol
• What Your Doctor Probably Doesn’t Know About HDL
• What Your Doctor Doesn’t Know: The Difference Between a Sterol and a Stanol
• C-Reactive Protein and Your Risk of a Heart Attack

Did you memorize your total cholesterol number? Did you know that lowering LDL cholesterol is the primary goal of treatment? Post your responses on the Cholesterol Management Community.

iStockphoto

Since I first decided in fifth grade that I wanted to be a heart surgeon, I have been on a mission to seek out the truth in medicine. Along my journey, I have learned that in many cases, there is no one absolute truth but many schools of thought on different medical topics.

However, the question that keeps rearing its head is: who are these thought leaders… these medical professionals that can have such an influence on health issues on a day-to-day basis and possibly cause havoc on a patient’s life by uttering a simple sentence that may be taken out of context or not?

The media often features doctors in name only, who don’t practice their trade or see patients, but may look good on TV, speak well or know the right people. Their credentials are never mentioned. Indeed, many doctors themselves don’t know where to turn to find the best possible answers to medical questions.

When I first started writing, I made a promise to present the newest and most accepted schools of thoughts on topics based on well-performed studies published in the most prestigious peer review journals. If I am just going to give my personal opinion, I will say so. That is the promise I make to my patients. It is within this context that I will continue to talk about resveratrol.

In part one, I discussed the basic thoughts on resveratrol and the reason for the current uproar in the media about this “miraculous ” new compound that is thought to keep people alive longer, help fight cancer and have positive effects on cardiovascular disease. I mentioned in part one the fact that the supplement industry is not well regulated and therefore, it is very difficult to know if the labeled dosages are accurate.

The anti-aging effects of resveratrol are being studied. Recent studies in laboratory mice have found increased survival and lower incidence of several diseases and conditions associated with aging, but the results are contradictory. Protective effects have been found in mice fed a high-fat or a low-calorie diet, but one study found that mice fed a standard diet beginning at age 12 months did not live longer.

One of the studies was reported in a New York Times article that described how a researcher was taking resveratrol himself and had founded a pharmaceutical company to develop chemicals that mimic the role of resveratrol but at much lower doses. GlaxoSmithKline acquired his company, Sirtris for $720 million in 2007 and hopes to develop “drugs that target the sirtiuns, a recently discovered family of seven enzymes associated with the aging process.”

After reviewing the animal studies, the highly respected Medical Letter concluded: “Resveratrol appears to produce some of the same effects as calorie-restricted diets that have reduced the incidence of age-related diseases in animals. Whether it has any benefit in humans remains to be established.”

Another supplement named protandim, which contains mainly green tea extract and tumeric, has been shown to reduce TBARS (a measure of cellular oxidative stress) by 40 percent in human subjects. Decreasing cellular oxidative stress could also have profound anti-aging effects, but the long-term results on humans for both resveratrol and protandim may never be known unless long-term prospective human studies are performed.

Many studies suggest that consuming alcohol (especially red wine) may reduce the incidence of coronary heart disease (CHD). Several studies have demonstrated that resveratrol has antioxidant properties. It is claimed that because resveratrol contains highly hydrophilic and lipophilic properties, it may provide more effective protection than other well-known antioxidants such as vitamin C and E. On the other hand, it is less effective than the antioxidants quercetin and epicatechin found in red wine.

Reduced platelet aggregation has also been demonstrated in studies on resveratrol, which could contribute to prevention of atherosclerosis. To date, however, most of the research on resveratrol’s antioxidant and anti-platelet properties has been done using test-tube or tissue-culture preparations and none have been tested in human trials. In addition, alcohol consumption raises triglyceride levels in the bloodstream. Besides the negative effect on the cardiovascular profile, alcohol use and high triglycerides can cause pancreatitis.

Resveratrol is also being studied to see how it affects the initiation, promotion and progression of cancer. With regard to tumor initiation, it has been shown to act as an antioxidant by inhibiting free radical formation and as an anti-mutagen in rat models. Studies related to progression have found that resveratrol induced human promyelocytic leukemia cell differentiation, inhibited enzymes that promote tumor growth, and exerted antitumor effects in neuroblastomas (the most common solid tumor in childhood).

In animal studies, resveratrol was effective against tumors of the skin, breast, gastrointestinal tract, lung and prostate gland. A recent review concluded that during the last decade, resveratrol has been shown to possess a fascinating spectrum of pharmacologic properties. Multiple biochemical and molecular actions seem to contribute to resveratrol effects against precancerous or cancer cells.

Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis and metastasis. The anticancer property of resveratrol has been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro; however, its role as a potentiator of breast cancer may limit its clinical use. There are numerous preclinical animal studies to evaluate the potential of this drug for cancer chemo prevention and chemotherapy currently underway.

In summary, epidemiologic studies can find associations between the consumption of foods or dietary supplements and various health outcomes. Animal experiments can demonstrate what can happen in the species tested. However, only clinical trials can determine whether supplementation is useful for humans. Resveratrol has not been tested in human clinical trials, and most clinical trials of other antioxidants have failed to demonstrate the benefits suggested by preliminary studies. Some substances — most notably beta-carotene — have even produced adverse effects.

My advice is to ignore the hype surrounding resveratrol until more is known!

Are you going to follow Dr. Richman’s advice to ignore the hype about resveratrol? Post your comments on the Cholesterol Management Community.