Noninvasive Methods to Assess Atherosclerosis: Part 3

Coronary Artery Calcium Using CT Tomography

I want to continue with our series of ways to help identify atherosclerosis in the body in order to better classify one's risk of a cardiovascular event or death. We already talked about using duplex ultrasound to measure carotid intima-media thickness and CT angiogram of the heart arteries. Now we are going to talk about using CT scan to identify the amount of calcium in the heart arteries (CAC scoring).

First of all, I want to make a general comment. As a heart surgeon think I have a unique perspective on coronary artery disease as I have seen and felt literally thousands of heart arteries. A cardiologist never sees the heart other than by an x-ray. The difference between a heart surgeon (cardiothoracic surgeon) and a cardiologist is often confusing to many people. Basically, a cardiac surgeon cuts and feels the heart in order to do a procedure and a cardiologist relies on x-rays only.

I also think it is important to say one thing about coronary artery atherosclerotic disease. Contrary to popular beliefs, when narrowing of the artery occurs, it occurs from inside the artery wall and pushes the inner layer called the intima outwards narrowing the artery. In other words, the cholesterol plaques do not start on the surface of the artery where the blood flows. Early plaques, which are most prone to rupture, contain little or no calcium. As the plaque matures, it may acquire calcium. Think of how bone develops. A young child has soft bones that are more pliable and less prone to fractures as compared to adult bones that are most rigid and are calcified. Instead, the cholesterol must be driven into the artery walls in what are called lipoproteins. To understand this whole concept, you can go to my website, Center for Cholesterol Management.

Now with these facts out of the way, we can talk about using CT scan to assess the amount of calcium in the atherosclerotic plaques in the artery. This is not a way to identify blockages in the artery. It is only a way to assess if there is coronary atherosclerosis. Like I said earlier, many plaques have little or no calcium. In 2007, the American College of Cardiology and American Heart Association published "Clinical Consensus Document on Coronary Artery Calcium Scoring Using Computerized Tomography". This paper was extremely thorough and gave final recommendations about when this method should be used. It is certainly overused by physicians and in fact will not be paid for by any private insurance or Medicare. When patients are evaluated as to risk of future cardiovascular events, they are classified as low risk, moderate risk, and high risk. Low risk is a 0-10% chance over a 10 year period, moderate risk 10-20% and high risk being 20% or greater. According to the expert committee, the only group may be considered for CAC scoring is the intermediate risk group. Here is the exact quote:

"The Committee judged that it may be reasonable to consider use of CAC measurement in such patients based on available evidence that demonstrates incremental risk prediction information in this selected (intermediate risk) patient group. This conclusion is based on the possibility that such patient might be reclassified to a higher risk status based on high CAC score, and subsequent patient management may be modified".

In addition, "CAC data are strongest for Caucasian, non-Hispanic men. The Committee recommends caution in extrapolating CAC data derived from studies in white men to women and to ethnic minorities."

The other problem is that not all centers have the same equipment and when they are being read by the doctor, there is tremendous observer variability. Ideally, if patients are going to get CAC scoring, they should be performed at the same place and looked at by the same person as the prior study. The clinical role of CAC scoring is not defined yet: however, it does offer promise as a screening tool or as a precursor to invasive angiography. At this point, further trials need to be done before it can be recommended for everyone.

Part 1: CIMT
Part 2: CT Angiogram of the Heart

Related Topics:

• WebMD Video: Predicting Heart Disease
• Cholesterol Management Message Board with Michael F. Richman, MD, FACS
• Get Cholesterol Management tips in your inbox

Noninvasive Methods to Assess Atherosclerosis: Part 2

CT Angiogram of the Heart

We talked about the use of Carotid Intimal Medial Thickness (CIMT) measurements as a way to assess if there is diffuse atherosclerosis in the arteries of the body in Part 1 of this series. Now let's talk about imaging the coronary arteries of the heart using a CT scan. About 10 months ago, there was a five-page article in the New York Times (Sunday edition) about this very topic. The article talked about the fact that this newer technology was being overused for financial gain while there was little evidence showing it was any better than the older technology, and it exposes the patients to the equivalent of several hundred chest x-rays and the resulting increased cancer risk.

Personally, I was delighted to see this article expose the truth about this overused method. Oprah and Time Magazine had raved about this type of angiogram prior to this article being written, but obviously they had not done their homework and explored the true factual data.

The role of CT angiogram of the coronary arteries in clinical practice is not defined yet and is absolutely not a screening tool for detecting blockages in the heart arteries in patients with no symptoms. Conventional coronary angiography is still the gold standard and is required by every cardiac surgeon in order to accurately assess the coronary arteries prior to heart bypass surgery. The American Heart Association does not endorse CT angiogram as a screening tool or as a precursor to standard coronary angiograms either.

In November 2008, an article in the New England Journal of Medicine stated that "Cardiac CT angiography misclassifies diagnosis of coronary stenosis in too many patients to replace conventional invasive imaging". This group from Johns Hopkins University found that it misclassifies approximately 13% of the areas of narrowing and also noted that, without evidence of outcome benefit, "a high resolution cardiac CT angiographic image of the heart is just another pretty picture." I couldn't agree more.

I would like to share a story about a patient I recently saw at my office in Los Angeles and his experience with the CT angiogram of the heart arteries. This Hollywood producer had gone to his cardiologist for routine stress testing. His doctor suggested that he have a CT angiogram of his heart instead. Since this is not a procedure covered by insurance companies, he spent several hundred dollars out of his own pocket to get the test done. The test came back and he was told that he had a 90% blockage of his LAD (Left Anterior Descending Artery) of his heart, a so-called "widow-maker" lesion. His cardiologist told him that he should not exercise until the doctor got back from a trip to Eastern Europe in three weeks, at which time some further testing would be done.

The patient came to see me during this time period and was frantic. I recommended to him that he should get some type of stress testing - which should have been done first before any thing else was done. His thallium stress test came back normal and did not show any area of his heart supplied by this artery as having limited blood flow.

It was at this time that his cardiologist came back from his trip. The patient called him and asked what he should do now. His cardiologist said that he would perform a standard coronary angiogram - which was normal.

The reason I am telling this story is to show what could have potentially happen and what did happen to this nice man. First of all, he had three tests when he could have had just one. The conventional angiogram has many risks, which I touched on in Part 1, and also may have led to him having an unnecessary angioplasty and stent placement. He also was exposed to the equivalent of nearly 1500 chest x-rays.

Stay tuned for Part 3; we will discuss CT Calcium Scoring of the heart arteries.

Related Topics:

• CT Scans for Clogged Arteries? Not Yet
• Cholesterol Management Message Board with Michael F. Richman, MD, FACS
• Get Cholesterol Management tips in your inbox

Noninvasive Methods to Assess Atherosclerosis

Part 1: CIMT

Cardiovascular disease remains the number one killer of both men and women. Does knowing this fact make it obligatory for health care providers to provide some type of warning system to possibly prevent a cardiovascular event or death? Let's look at the various techniques that are currently in use to potentially identify early atherosclerosis which would then permit early aggressive treatment. I do understand that many people who read my blog have different levels of understanding of these difficult medical issues. While I will try to keep it simple, I believe it is important to do it in such a way as to not trivialize such an important topic.

Invasive coronary angiography (angiogram or cardiac catheterization) is still the gold standard to identify clinically significant coronary artery disease. Like all invasive procedures, there are inherent risks associated with the procedure - risks that include heart attack, stroke, death, damage to the artery in the arm or groin used as the puncture site, and kidney failure to name a few.

I believe that many cardiologists indiscriminately perform angiograms of the heart arteries for reasons that are clearly not supported by the literature. With this said, I prefer to perform noninvasive testing in order to identify patients at risk. If after following a treatment algorithm, it is felt that coronary angiogram becomes necessary; it then can be done in accordance with well-accepted indications.

Noninvasive Methods
Let's first look at carotid intima-media thickness, also know as CIMT. This involves measuring the thickness of two concentric (circular) layers of the neck arteries using duplex ultrasound. To be more precise, it measures the thickness of the first two layers of the mid-portion of the common carotid artery. CIMT was first reported as a surrogate or substitute marker for atherosclerosis in 1986. This was a comparison between autopsy studies and what was found in B-mode ultrasound studies. There was a measurement error of less than 20% in 77% of the subjects studied. In a follow up study, they found that patients with high cholesterol had increased CIMT augmented by including traditional risk factors. Fourteen years later, the American Heart Association deemed CIMT the only acceptable noninvasive method for assessment of cardiovascular risk. It is thought that any increase in CIMT is a reactive process secondary to shear stress and pressure within the artery from hypertension and plaque formation.

The ARIC trial is the largest CIMT observational cardiac endpoint trial to date. In 13,870 middle-aged adults, CIMT measurements were increased in those patients with coronary artery disease. Quantification studies showed that a .2mm increase in CIMT yielded a 33% relative risk increase in heart attack and 28% for stroke. Similarly, in both the CHS study and Rotterdam study, increased CIMT correlated with subclinical atherosclerosis. Since CIMT is a recognized marked of cardiovascular risk, it is used as a primary endpoint in clinical trials. The beneficial effects of cholesterol lowering on CIMT progression have been demonstrated in ARBITER, ASAP, and ACAPS. In the ENHANCE study, the results were not accurately portrayed by the media and I have previously written about the actual results on my blog. Additional studies using different blood pressure medicines are ongoing in order to see their effect on CIMT.

The main problem with measuring CIMT is that there has been significant inter-observer variability. Technical advancements in B-mode ultrasonography have reduced this problem.

To be continued...

Related Topics:

• Low Heart Disease Risk? Test May Show Otherwise
• Cholesterol Management Message Board with Michael F. Richman, MD, FACS
• Get Cholesterol Management tips in your inbox

Red Yeast Rice - Buyer Beware!

I have had an increasing number of patients come to see me who are taking Red Yeast Rice (RYR) as the only means to treat their high cholesterol. Many people make the assumption that this is a "natural medicine" and that it is completely safe to use and actually works.

Unfortunately, RYR is not the wonder drug that many folks think that it is and may actually be harmful. First, one must remember that in 2008, there were many products manufactured in China that were found to be tainted with lead and melamine, to name a few of the contaminants.

Red Yeast Rice extract is the fermented product of rice on which red yeast has been grown . The active ingredient in red yeast rice is believed to be Monacolin K, an agent reported to be identical to lovastatin (a commonly prescribed statin). Like satins, red yeast has been found to directly reduce lipids. There is little doubt that the proprietary preparation of red yeast rice, known as Cholestin favorably alters lipids. However, due to legal issues, this preparation is no longer commercially available in the US. In 1998, the FDA determined that red yeast rice did not conform to the definition of a dietary supplement under the 1994 Diet supplement and Health Education Act (DSHEA). This act states that marketed dietary supplements cannot contain a compound already approved as a drug (in this case, lovastatin) unless the substance was available commercially before the drug's approval.

At present, Cholestin is still available in Canada, Europe and Asia - however, great caution should be exercised because Cholestin has been reformulated and no longer contains the important Red Yeast Rice extract, but rather polymethoxylated flavones extracted from citrus fruits, geraniol and marine fish oils. It is unclear if this or other proprietary preparations of red yeast extract will provide the same lipid effects. The FDA has issued a warning to consumers regarding three brands of red yeast rice. For more information, visit the FDA website and type in red yeast rice in the search box.

As a result of a study published in the June 15, 2008 issue of the American Journal of Cardiology, the National Lipid Association (NLA) felt compelled to write an official statement on this RYR study. This study suggested that a new ingredient of RYR, called Xuezhikang (XZK), may have significant benefits. The published study was a randomized, double-blind, placebo study conducted in Chinese hospitals on 4,870 patients who had a previous heart attack within the past 5 years. The primary endpoint was the occurrence of a major coronary event or death from coronary or cardiac causes. The striking findings of this study are the 45% reduction of the relative risk of major coronary events and the statistically significant reductions in CV and total mortality The NLA recommended that physicians and patients should beware that the composition of this product is not yet known and any future use will depend on the results of ongoing studies.

XZK is produced by the Beijing WBL Peking University Biotech Co. Ltd and is the purified extract of Chinese RYR with multiple components. This product is not sold in the USA, lacks FDA approval, and is not identical to other products sold in the USA as "red yeast rice". This does not mean that this particular brand is not brought into this country illegally. Like the product known as Cholestin, XZK contains lovastatin, plants sterols, and isoflavones. At the present time, it is not known to what extent, if any, lipid- lowering accounts for treatment benefit.

To summarize the current thought on this preparation and all other types of RYR,

1. Physicians should not advise patients to take any RYR supplement as efficacy has not been proven for any indication.


2. If you are taking a medicine for cholesterol management, continue to take your prescription. Do NOT add any RYR to your current medications as adverse effects may be more likely.


3. RYR should not be substituted for statins. The active ingredients of any of the preparations currently sold in the USA are unknown.

Related Topics:

• Quiz: Do You Know How to Lower Your Cholesterol?
• Cholesterol Management Message Board with Michael F. Richman, MD, FACS
• Get Cholesterol Management tips in your inbox

Omega-6 Polyunsaturated Fatty Acids & Your Heart

There is a large body of literature suggests that higher intakes of omega 6 polyunsaturated fatty acids (PUFAs) reduce risk for coronary heart disease (CHD). The American Heart Association just published a science advisory in Circulation on January 27, 2009, titled Omega-6 Fatty Acids and Risk for Cardiovascular Disease. There are some noted physicians and medical groups that have recommended substantial reductions in the intake of PUFAs due to this possible association.

Linoleic acid (LA) is the primary dietary O-6 PUFA and cannot be synthesized by human beings. Therefore it has to come from food sources. While there are no firm requirements for the amount of daily intake, it is felt that .5-2% of the total energy is sufficient. The LA can be converted into something called linolenic acid. This can be converted into the metabolically active O-6 PUFA called arachidonic acid (AA). This is very important as I will explain a little later. LA comes primarily from vegetable oils like corn, sunflower, safflower, and soy. According to the National Health and Nutrition Survey data indicates that usual intake of LA in adults greater than or equal to 19 years of age is 6.7% of energy.

The arguments for the reductions in the intake are based on the assumption that because there is an inflammatory component to coronary artery disease (CAD) and AA is the substrate for the production of a variety of pro-inflammatory mediators, reduction in the intake of LA should reduce the inflammatory potential and therefore lower the risk for CAD. Despite this fact, O-6 PUFAs also have anti-inflammatory properties. In one study, when healthy volunteers were given 7 times the usual intake of AA in a 7-week controlled feeding study, no negative inflammatory response was observed. Other studies also support this finding. At present, there is little direct evidence of a net pro-inflammatory, pro-atherogenic effect of LA in humans.

The cholesterol lowering effect of LA is well established. Epidemiologically, the replacement of 10% of calories from saturated fatty acids with O-6 PUFAs is associated with an 18 mg/dl decrease in LDL cholesterol which is greater than that observed with similar replacement with carbohydrate. These findings confirm a beneficial effect on cholesterol lowering of O-6 PUFAs beyond that produced by the removal of saturated fatty acids. Favorable effects of higher LA intake on cholesterol levels are thus well documented and would predict significant reductions in CAD risk. Nevertheless, not all studies support a beneficial effect of LA of coronary heart disease risk markers. For example, an angiographic study published in 2004 reported a direct association between PUFA intakes and artery narrowing in women with CAD. Like many studies, this particular study did not evaluate outcomes so indeed it is possible that this association did not result in increased morbidity and mortality.

In summary, AHA advisory was undertaken to summarize the current evidence on the consumption of PUFAs and CAD risk. Data from randomized trials, case-control and cohort studies, and long term animal feeding experiments indicate that eating at least 5-10% of energy from O-6 PUFAs reduces the risk in relation to lower intakes. The data also suggest that higher intake seems to be safe and even more beneficial. To reduce PUFA levels from their current levels would be more likely to increase, than to decrease, risk for CAD.

Related Topics:

• Expert Panel: Omega-6 Won't Hurt Heart
• Fat Facts: Good Fats vs. Bad Fats
• Get Cholesterol Management tips in your inbox

Sterols and Stanols (Part 2)

In the last post, I gave a brief overview of sterols and stanols and how they are absorbed in the intestine. I want to start this post by talking about 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, so 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 - ABCG5/G8.

As I previously stated, only about 50-55% of ingested cholesterol makes it into chylomicrons in order to be transported to the liver for processing. These 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. 70% of the cholesterol in the body is transported as an ester, not as free cholesterol, and 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 (no where 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.

Related Topics:

• Understanding Cholesterol Problems - the Basics
• Women and Coronary Artery Disease
• Cholesterol Management Message Board

Sterols and Stanols (Part 1)

I hope everyone had a nice New Year's celebration! I have wanted to write on this topic for several months, but every time I started, there was a new question on my message board that I felt had to be addressed more in depth. I will do this in two or three different parts. My goal is to not only educate you about these substances, but also make people aware that in some situations sterols other than cholesterol can cause atherosclerosis. I know that most of the public has no idea about phytosterols, but you may have seen the term on some brands of baby aspirin. I am also 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 it. This difference minimizes stanol absorption in the intestines.

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

We consume many sterols from plant sources (sitosterol, campesterol, and stigmasterol), shellfish (desmosterol and fucosterol) and animal sources (cholesterol). If sterols or stanols are esterified (combined with fatty acids), then they can be incorporated into margarine. 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) and then they are absorbed by passive diffusion into the intestinal cells. Passive diffusion is a biological principle that substances flow through a semi-permeable membrane 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; but some people are what is termed "hyperabsorbers" (they absorb 60-80%) and some are "hypoabsorbers" (they absorb less than 50%).

Next: While the food and pharmaceutical industries are pushing sterols in the diet, they may be in fact causing CAD. Why and how can phytosterols do this? Let's look at the data showing that this occurs. I will also talk about the fact that atherosclerosis does not occur with stanol ingestion.

Related Topics:

• Take Steps to Reduce Cholesterol
• WebMD Cholesterol Management Health Center
• Cholesterol Management Message Board