Cholesterol Management 101

By Michael F. Richman, MD, FACS, FCCP

So, your doctor looks at your blood test and says, “You have high homocysteine levels.” What does that mean? And what should you do about it?

Homocysteine is a common amino acid (one of the building blocks that make up proteins) found in the blood and is acquired mostly from eating meat. I have written before about the possible role of elevated homocysteine levels in causing heart attacks or strokes. High levels of homocysteine are related to the early development of heart and blood vessel disease. In fact, it is considered an independent risk factor for heart disease. High homocysteine is associated with low levels of vitamin B6, B12 and folate and kidney disease.

Research has shownthat both folic acid and B vitamins lower homocysteine levels, and many researchers and physicians believed that this would lower a patient’s overall cardiovascular risk. Not so.  Recently, a study called the Women’s Antioxidant and Folic Acid Cardiovascular Study found that supplemental folic acid and B vitamins do not lower the risk for important vascular events in women who are otherwise at high risk for such events, even though these supplements lower homocysteine levels.

What is high risk?  A minimum of three “cardiac risk factors” puts anyone at high risk.  They are:  high cholesterol, hypertension, metabolic disorder,  a family history of heart disease and a prior heart-related event, such as heart attack or stroke. Lifestyle indicators include obesity and cigarette smoking.

The study was a randomized, double-blind, placebo-controlled trial conducted in Boston that  began in 1998 with 5,442 women, age 40 and older with a history of cardiovascular disease, and studied them over the course of seven years.  Study participants received either a folic acid/B vitamin combination or a matching placebo.  What they found was startling to the medical community.  Over the course of 7.3 years, there was a similar incidence of heart attacks and strokes between the group that received the vitamins and the one that didn’t.  In fact, 406 women in the treatment group and 390 in the placebo group experienced at least one “event” of heart attack or stroke.

These findings  are identical to those seen in the Heart Outcomes Prevention Evaluation trial, the Norwegian Vitamin Trial and the Vitamin Intervention for Stroke Prevention trial, among others (which enrolled mostly men), even though the therapy is successful in reducing homocysteine levels. While numerous observational, epidemiological studies have confirmed that elevated homocysteine is a predictor of cardiovascular risk, it has become very clear that lowering homocysteine levels has little to no outcome for men or women at high risk of cardiovascular disease.  So, why are people with elevated homocysteine levels at high risk for cardiovascular disease?  Medical researchers are working on this one.  As a heart surgeon, I see clogged arteries every week, up close and personal.  It makes you wonder, is homocysteine really the culprit?  Or, is it just the result of something else that is going on in the body?   I will keep you updated as new trials and information are released on this important subject.

By Michael F. Richman, MD, FACS, FCCP

In the October 18, 2011 issue of the Journal of the American College of Cardiology, Dr. Susanna Larsson of the National Institute of Environmental Medicine in Stockholm, Sweden stated in a news release that women who ate up to two bars of chocolate per week showed a significantly reduced risk of stroke. Those women who ate up to a half of a bar or even smaller amounts also had a reduction in the stroke rate.

The study included 33,372 women who were asked to report how often and how much chocolate and other foods they consumed over the course of a year.  Investigators listed the women into categories ranging from those who never ate chocolate to those who indulged three or more times a week and examined the risk of stroke over a mean follow-up of 10 years, adjusting for major risk factors associated with stroke. Women who reported having been diagnosed with hypertension did not show any significant benefit; however, those without hypertension and higher chocolate consumption seemed to show a decrease in strokes. The researchers identified 1549 strokes in their study.

I know this sounds great to chocolate lovers, but there’s a problem with the way the study was conducted. The gold standard of any trial is to have what is called level 1 evidence. This means that the study was randomized, blinded to the researchers, controlled, and resulted in a statistically significant primary endpoint. An example of this would be a study comparing two drugs or a drug versus a placebo in which neither the patient nor the investigator knew what the patients were being given. The study is rigorously controlled and the goal of the study (primary endpoint) is clearly reached with statistical significance. This study did not appear to follow such strict standards.

First, the women were given a food frequency questionnaire and from this these wonderful results were reported. I don’t remember what I ate yesterday let alone keeping track of everything for an entire year. Then, a statistician was brought in to adjust the data and was somehow able to exclude anything else that may impact stroke rates. The result is a study saying that Swedish women who ate a certain amount of chocolate had lower stroke rates than those who did not. The association between chocolate consumption and stroke was stronger the higher the concentration of cocoa in the chocolate.

So, what are the health properties of chocolate? Researchers have long thought that cocoa, the main ingredient in chocolate, may have cardiovascular benefits due to the flavonoids in cocoa and their antioxidant properties. Antioxidants protect the body from damage caused by free radicals and can suppress oxidation of low-density lipoprotein particles, which are the carriers of the bad cholesterol in the blood. Dark chocolate consumption has also been shown to reduce blood pressure, which is a major risk factor for stroke, but the data is limited at best.

Now the question from chocoholics is: how much should one eat? Chocolate, and especially chocolate bars, are high in sugar, fat and calories and should therefore be consumed in moderation if at all. Dark chocolate, with a concentration of greater than 50% cocoa, is usually lower in sugar and has higher flavonoid content. Indulgence in chocolate in moderation remains a reasonable approach to satisfy a craving. Eating a healthy diet, controlling blood pressure and cholesterol levels, and modifying other risk factors for stroke is the best approach for now.

In early September, the results of a study known as the SATURN statin trial were released. Since that time, I have had several patients ask me which statin drug is the best to remove cholesterol plaques. Plaques lead to blockages from the arteries of the heart. This is a very interesting question that I have been asked before by many patients. The simple answer is that to date, there are no published studies that have looked at whether or not being able to remove plaques from arteries in the heart, also know as atheromas, can lower the chances of having a heart attack. This is known as outcome data.

I find myself spending more and more time with patients trying to explain what they heard or didn’t hear or read on television or the newspaper regarding cholesterol studies. There are many studies published every day on many different topics. The majority of the papers are not published in journals that are reviewed by doctors who practice in the same field as the paper’s author. These are what as known as “throw away” journals as the often lack credibility. Articles that are published in “peer-reviewed” journals are generally regarded as those that have undergone rigorous scrutiny before being accepted for publication.

With that as a background, I want to talk about SATURN. This trial compared two different statin drugs in 1,300 patients. It looked at how the drugs removed some plaque from the atheroma. Specifically, they looked at the change in atheroma volume before being treated with drugs and then after two years on treatment. They put a catheter in the heart arteries and used ultrasound to measure the change in the volume of the plaque.

The two statins compared were high dose Crestor and Lipitor. The results showed that the two statins were the same in the amount of plaque reduction, but a numerical result was not given. The information will be presented at the American Heart Association meeting in November.

The main reason I brought up this trial is because this study was just “a pretty picture”. What does this mean? It means that the authors had no outcome results to report. Although the plaque volume decreased, there is no data looking at if there was a reduction in non-fatal heart attacks, fatal heart attacks, or overall cardiovascular death.

So how does the information from the SATURN trial help us? In my view, it does’t provide us with any useful information until we can show that removing plaque will result in an outcome that will provide useful data which will result in a treatment that will change an outcome and benefit patients.

NBC Nightly News recently featured a story about C-reactive protein as a “simple blood test that could save women’s lives.” As WebMD’s medical expert on cholesterol and a heart surgeon, I want to explain the role of C-reactive protein as a so-called biomarker of heart disease. While the use of this blood test may be useful in helping to determine one’s risk of a possible heart attack or a stroke in the future, it is simply one of many new and emerging biomarkers that your doctor can use to help determine your risk.

C-reactive protein (CRP) is found in the blood. Its levels rise in response to inflammation. The more inflammation, the higher the CRP.

Now lets talk about inflammation and its role as a cause of events like heart attacks and stroke. It’s been well documented that both inflammation throughout the body as well as inflammation specific to the blood vessels play a prominent role in events leading to the build up and rupture of plaques in a person’s arteries. Exactly how this occurs is under great debate and being widely studied.

While CRP and its role in inflammation was discovered in the 1930s, it has received more attention in medical journals and in the media over the past 10 years. At some points, experts thought CRP was a more important test that the traditional cholesterol panel that looks at levels of good and bad cholesterol. They also thought that CRP testing alone was a better indicator than measuring LDL-C (the bad cholesterol) in predicting heart attacks and strokes.  

More than 25 studies published during the last 10 years have provided strong evidence that C-reactive protein predicts heart risk in various scenarios, not only in initially healthy subjects, but also in those who have established atherosclerosis (clogging of the arteries). However, two years ago, in July 2009, The Journal of the American Medical Association analyzed data from approximately 100,000 people and concluded high levels of C-reactive protein does not cause heart disease. 

Researchers have also found out that lowering C-reactive protein does not protect people from developing heart disease. Many patients who had “low cholesterol” but had high CRP were treated with statin drug therapy to try to lower CRP. It was hoped that this would lower the rate of heart attacks and strokes. As of today, we do know that lowering CRP has not altered the rate of strokes or heart attacks.

A large study authored by more than 35 noted MDs and PhDs showed there are people who produce more C-reactive protein throughout their lives and others who produce less. The theory goes, if C-reactive protein causes heart disease, those who make more would have more heart disease. The study did not find this. There was 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 short, C-reactive protein is simply a marker of inflammation and NOT an accurate predictive test for heart disease risk. 

 The U.S. Preventive Services Task Force announced recently supported this finding, saying that CRP alone was not enough to determine heart disease risk. 

Every day I have patients who read news articles, or see news stories on a new test. Many are now asking about their C-reactive protein. Thanks to misleading and often half researched news articles and reports, many think that this single test is absolutely critical to prevent a heart attack. I explain to them, as I have done here, that while it is important, it is only one biomarker used to help determine their risk. Despite multiple attempts to develop drugs to target and lower C-reactive protein, many experts now feel that it is time to abandon that search and concentrate on finding better drugs to prevent the build up of cholesterol in the artery wall.

Medical training is one of the most difficult times a new doctor has to endure in their quest to become a licensed and board certified physician or surgeon. Medical residencies traditionally require lengthy hours of their trainees. The American public and the medical education establishment increasingly recognized that such long hours were counter-productive, since sleep deprivation increases rates of medical errors.

In 2003, the Accreditation Council for Graduate Medical Education (ACGME — the society that accredits training programs) addressed the current residency training and duty hour requirements. The elements highlighted include patient safety, resident wellness, and the resident training experience.

After lengthy debates among various medical societies, in 2007, regulations capped the work-week at 80 hours for medical residents in training. The ACGME also mandated that overnight call frequency to no more than one overnight every third day, 30-hour maximum straight shift, and 10 hours off between shifts. While these limits are voluntary, adherence has been mandated for the purposes of accreditation of the residency. (more…)

Familial Hypercholesterolemia (FH) is a group of genetic disorders that result in severe elevations of blood cholesterol levels. Despite being of one the most common serious genetic disorders, few people know about FH unless their life is affected in some way.

The prevalence of FH is 1 in 300 to 500 in many populations. There are over 620,000 FH patients currently living in the United States. Many of these people are unaware that their risk of premature coronary heart disease is elevated about 20-fold in patients that have not been treated. (more…)

I think it is extremely important to talk about the AIM-HIGH trial failure since it has dominated the news and disappointed many clinicians.  The AIM-HIGH study analyzed whether raising HDL through the combination statin and niacin therapy would reduce the risk of having a heart attack in people with established heart disease. But the therapy showed no benefit and the study was brought to an abrupt halt more than a year before the anticipated end date. (more…)

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…)