Johns Hopkins researchers have developed a more accurate way to calculate low-density lipoprotein (LDL) cholesterol, the so-called “bad” form of blood fat that can lead to hardening of the arteries and increase the risk of heart attack and stroke. If confirmed and adopted by medical laboratories that routinely calculate blood cholesterol for patients, the researchers say their formula would give patients and their doctors a much more accurate assessment of LDL cholesterol.
“The standard formula that has been used for decades to calculate LDL cholesterol often underestimates LDL where accuracy matters most — in the range considered desirable for patients at high risk for heart attack and stroke,” says Seth S. Martin, M.D., a cardiology fellow at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Martin is first author of the study detailed in a Nov. 19, 2013 article in the Journal of the American Medical Association.
Many studies have shown that higher levels of LDL cholesterol signal greater risk of plaque accumulating in heart arteries. Since 1972, a formula called the Friedewald equation has been used to gauge LDL cholesterol. It is an estimate rather than a direct measurement. However, physicians use the number to assess their patients’ risk and determine the best course of treatment.
The Friedewald equation estimates LDL cholesterol with the following formula: total cholesterol minus HDL cholesterol minus triglycerides divided by five. The result is expressed in milligrams per deciliter. That equation, the researchers say, applies a one-size-fits-all factor of five to everyone; a more accurate formula would take specific details about a person’s cholesterol and triglyceride levels into account.
Using a database of blood lipid samples from more than 1.3 million Americans that were directly measured with a traditional and widely accepted technique known as ultracentrifugation, the researchers developed an entirely different system and created a chart that uses 180 different factors to more accurately calculate LDL cholesterol and individualize the assessment for patients.
“We believe that this new system would provide a more accurate basis for decisions about treatment to prevent heart attack and stroke,” says Martin.
HDL vs. LDL
All cholesterol isn’t the same. There’s HDL cholesterol (“good”) and LDL cholesterol (“bad”). Both types of cholesterol molecules travel through the bloodstream in globular packages in combination with lipoproteins, and they perform different functions.
What is HDL?
High-density lipoproteins (HDL) are small, dense molecules responsible for transporting cholesterol to the liver.
HDL is good for your body because it helps remove cholesterol from the arteries and protects against dangerous blockages (plaques) in the arteries. HDL cholesterol is also less likely than other forms of cholesterol to oxidize and leave sticky plaques on artery walls.
“Your good HDL cholesterol hustles your bad LDL cholesterol to your liver to disposal before it can plant itself like barnacles in your arteries,” say doctors Mehmet C. Oz, M.D., and Michael F. Roizen, M.D.
People who exercise, don’t smoke, and maintain a healthy weight tend to have higher levels of this “good” cholesterol. Low HDL levels can be a risk factor for coronary heart disease (CHD), while high levels (>60 mg/dL) help reduce CHD risk.
What is LDL?
Low-density lipoprotein (LDL) carries the majority of cholesterol through your bloodstream and delivers it to the cells of the body. These molecules are larger, less dense, and less stable than HDL. They readily oxidize and deposit plaques on arterial walls to likely to clog arteries and lead to cardiovascular disease. That’s why LDL is known as the “bad” cholesterol.
Results of the new study are built on research by the same authors from the Johns Hopkins University School of Medicine and published in the Journal of the American College of Cardiology. In that study, the researchers compared samples assessed using the Friedewald equation with a direct calculation of the LDL cholesterol.
They found that in nearly one out of four samples in the “desirable” range for people with a higher heart disease risk, the Friedewald equation was not accurate.
“As a result, many people - especially those with high triglyceride levels - may have a false sense of assurance that their LDL cholesterol is at an ideal level. Instead, they may need more aggressive treatment to reduce their heart disease risk,” says Steven Jones, M.D., director of inpatient cardiology at The Johns Hopkins Hospital and a faculty member at the Ciccarone Center who is the senior author of the study.
The lipid profiles used for the study were from a laboratory in Birmingham, Ala., which provides a detailed analysis of samples sent in by doctors across the country. Except for the age of people on whom the samples were based (59 years on average) and the gender (52 percent of the samples were from women), the patients were not identifiable to the researchers. That database was almost 3,000 times larger than the sample used to devise the Friedewald equation 43 years ago.
What Is Cholesterol?
Cholesterol is a fat, or lipid. It is also a sterol, from which steroid hormones are made. If you held cholesterol in your hand, you would see a waxy substance that resembles the very fine scrapings of a whitish-yellow candle. Cholesterol flows through your body via your bloodstream, but this is not a simple process. Because lipids are oil-based and blood is water-based, they don’t mix. If cholesterol were simply dumped into your bloodstream, it would congeal into unusable globs. To get around this problem, the body packages cholesterol and other fats into minuscule protein-covered particles called lipoproteins (lipid + protein) that do mix easily with blood. The proteins used are known as apolipoproteins.
The fat in these particles is made up of cholesterol and triglycerides and a third material I won’t discuss much, phospholipid, which helps make the whole particle stick together. Triglycerides are a particular type of fat that have three fatty acids attached to an alcohol called glycerol—hence the name. They compose about 90 percent of the fat in the food you eat. The body needs triglycerides for energy, but as with cholesterol, too much is bad for the arteries and the heart.
A Lipoprotein by Any Other Name
The two main types of lipoproteins important in a discussion on heart disease are low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Though the names sound the same, these two particles are as different as night and day. The differences stem from their densities, which are a reflection of the ratio of protein to lipid; particles with more fat and less protein have a lower density than their high-protein, low-fat counterparts. There are countless other lipoproteins, some of which I’ll discuss in later chapters, but in order to get a basic understanding of how cholesterol affects your body and how the food you eat affects your cholesterol levels, LDL and HDL are the ones to start with.
Low-Density Lipoproteins (LDL)
In most people, 60 to 70 percent of cholesterol is carried in LDL particles. LDL particles act as ferries, taking cholesterol to the parts of the body that need it at any given time. Unfortunately, if you have too much LDL in the bloodstream, it deposits the cholesterol into the arteries, which can cause blockages and lead to heart attacks. That’s why people refer to LDL as the “bad” cholesterol. The good news is that the amount of LDL in your blood-stream is related to the amount of saturated fat and cholesterol you eat. So, most people can decrease their LDL if they follow a reduced-fat diet. When you get a fasting cholesterol test, your doctor should test for the level of LDL cholesterol.
High-Density Lipoproteins (HDL)
HDL is basically the opposite of LDL. Instead of having a lot of fat, HDL has a lot of protein. Instead of ferrying cholesterol around the body, HDL acts as a vacuum cleaner sucking up as much excess cholesterol as it can. It picks up extra cholesterol from the cells and tissues and takes it back to the liver, which takes the cholesterol out of the particle and either uses it to make bile or recycles it. This action is thought to explain why high levels of HDL are associated with low risk for heart disease. HDL also contains antioxidant molecules that may prevent LDL from being changed into a lipoprotein that is even more likely to cause heart disease. Lifestyle changes affect HDL levels - exercise can increase them, while obesity and smoking lower them. As for diet, in general, the high-fat diets that raise LDL also raise HDL, while low-fat diets lower both. However, by carefully choosing the right foods, you can eat a diet that lowers LDL without lowering HDL.
Jones, who originated the idea to use the large laboratory database to assess the Friedewald equation, says the information was provided by the lab at no cost. The lab, Atherotech, did not provide any funding for the research or input on the calculations or study article. The database used in the study is registered on the website http://www.clinicaltrials.gov and will be an important resource for ongoing scientific investigation.
Jones and Martin are listed on a patent pending for the new system, which was filed by The Johns Hopkins University. Dr. Martin is supported by the Pollin Cardiovascular Prevention Fellowship, as well as the Marie-Josée and Henry R. Kravis endowed fellowship.
In addition to Martin and Jones, other researchers on the study were: Michael J. Blaha, Mohamed B. Elshazly, Peter O. Kwiterovich and Roger S. Blumenthal from the Johns Hopkins University School of Medicine, and Peter P. Toth from the University of Illinois College of Medicine at Peoria.
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Ellen Beth Levitt
Johns Hopkins Medicine