Skip to main content
Premium Trial:

Request an Annual Quote

Quest Moves to Cholesterol Test Better Suited to Current Treatment Practices


NEW YORK (360Dx) – Quest Diagnostics' decision to move to a new cholesterol calculation method will give physicians more accurate readings of "bad cholesterol" when treating high risk patients, the company said.

Quest announced its decision last month to move to the new nonfasting cholesterol test, which relies on a new calculation method that replaces the Friedewald equation, the standard cholesterol test in laboratories in the US since 1972.

"There were always concerns that Friedewald had inaccuracies. It was developed back in the early '70s and was particularly inaccurate at the lower end LDL levels," said Gerard Abate, Quest's executive director of medical affairs, referring to low density lipoprotein cholesterol, also called bad cholesterol. "With goals tightening toward more aggressive management, when your LDL levels are lower than 70, inaccuracies become greater."

The Friedewald test also had inaccuracies in measuring high triglycerides, Abate added.

"As your triglycerides increased, the variability in your LDL increased as well, and as we looked for tighter control of LDL on the low end and high end, it was important to have a calculator that could work for all," he said.

The new algorithm, developed by Seth Martin, assistant professor of medicine at Johns Hopkins University School of Medicine, produces more accurate LDL-C measurements by replacing a standard calculation with calculations that are personalized for different patients. The issue, Martin said, is that one part of the Friedewald equation estimates a factor of five for the ratio of triglycerides to very low density lipoprotein cholesterol, or VLDL-C, when, in fact, that ratio can vary significantly.

"It was using the same number for everybody, a one-size-fits-all approach," Martin said of the Friedewald equation. "The only difference is instead of dividing by five, we personalized the factor. It's still using the same data and the same information, but instead of dividing by five, it is going to pick one out of 180 different factors for that person."

Martin used a big-data approach, tapping a database of more than 1 million cholesterol tests measured through ultracentrifugation from Atherotech, a lab in Alabama that has since become VAP Diagnostics Labs. Ultracentrifugation directly measures LDL, but is not broadly available as a standard cholesterol test. Martin and his team were able to use the database of direct LDL measurements to create 180 different triglyceride-to-VLDL-C ratios matched to different lipid profiles. The new model selects a factor that most closely matches the patient to divide by, instead of the universal factor of five.

Martin and his colleagues published a study comparing the results of the calculation method they developed with the Friedewald equation in the Journal of the American Medical Association 2013.

A non-fasting method

Because the Friedewald equation had inaccuracies in measuring high triglycerides, it was less accurate if patients had eaten prior to having their cholesterol tested.

"One of the things that will raise the triglycerides is being non-fasting. Being in a fed state, triglycerides tend to be a little bit higher, so just simply being postprandial will give you additional departures from assumptions made in the Friedewald equation beyond those seen with hypertriglyceridemia," said Eliot Brinton, president of the Utah Lipid Center in Salt Lake City and a member of the board of directors of the national Lipid Association.

The reason the Friedewald equation was inaccurate in measuring high triglycerides was due to its one-size fits all approach to estimating the ratio of triglycerides to VLDL-C, Martin explained.

"Because our algorithm adapts to triglycerides, because the factors it divides by take into account the triglyceride level, it is able to adapt to the non-fasting state," Martin said.

As a non-fasting cholesterol test, the calculation developed by Martin will make cholesterol testing easier to administer, Martin noted.

"It has practical implications. A patient comes in to see the doctor in the afternoon and has to come back for fasting labs in the morning, whereas with this test, they could just get it done on the spot and get accurate results," he said.

There has been increased acceptance of non-fasting cholesterol tests in recent years, with some broad studies showing that the amount of discrepancy in fasting and non-fasting cholesterol measures may not be that significant, Brinton said.

"The problem I have in that regard is that I treat patients one at a time. When I see one patient, it's not the same as having a large population put together," he said. "A lot of the variability you might see with a given patient, on a given day, with a given meal, at a given time after the meal is smoothed out in a large population.

The new test reduces the risks of individual variability for non-fasting tests, he noted.

Cholesterol health and treatment trends

The Friedewald equation's inaccuracies in measuring high triglycerides is particularly concerning given recent health trends, Brinton noted.

"High triglycerides is driven by [being] overweight and obesity but also by diabetes," he said. "Of course, there is more overweight, obesity and diabetes, so high triglycerides tend to be becoming more common."

In addition, Brinton noted, trends in how high triglycerides are treated are shifting.

"We are becoming more concerned about high triglycerides and we are becoming more aggressive in treating them," he said. "Part of it is a secular trend, where there is an increase in the levels over time, but part of it is we are understanding more clearly that this is a problem. We now have the tools to treat a high triglyceride level so we are treating it more often."

Similarly, the Friedewald's inaccuracies on the low end of LDL levels is increasingly significant as new medications have made it easier to treat LDL to lower levels and studies have shown benefits of more aggressive treatment.

Clinical trials of the new injectable cholesterol medicine known as PSCK9 inhibitors, the medication Ezetimibe (Zetia), and more aggressive use of statins show that it is beneficial to treat patients down to lower levels, according to Martin.

"It used to be thought if you get someone down under 100, that's great, nothing more to do. Now we know that by getting people to less than 70, they have better outcomes," Martin said.

Abate said the most aggressive treatments have taken levels way lower than that.

"We have actually seen some cases where we have a negative report of an LDL level because with Friedewald you can get a negative number if LDL is very low," he said. "The new calculator that Dr. Martin developed corrects for that so you don't get those negative readings."

Quest's conversion

Abate was familiar with Martin's new calculator prior to joining Quest, in part because he had previously worked for Atherotech, the lab company whose database of ultracentrifugation lipid panels Martin used to develop his algorithm.

"I have been at Quest almost three years and when I first came to Quest I brought it up to the franchise that it would be helpful for us to look at the basic lipid panel and to change the calculator," Abate said.

Upon receiving approval from Quest and from Martin to move forward with adopting the test, Abate began working with patent lawyers at Johns Hopkins to negotiate a license for the calculator.

"I didn't want an exclusive license because I feel this should be the standard," Abate said. \

Quest is currently the only lab in the US offering the calculation devised by Martin, Abate said, adding that other labs have contacted the company recently to inquire about how to license the test from Johns Hopkins. Outside of the US, the test is also being offered through a lab company in Brazil.

As the new method is simply a new calculation, and not a new testing technology, it is relatively simple to roll out, Martin said. Doctors will receive similar cholesterol test results to what they had received with the Freidewald equation, except in areas where the Friedewald equation's LDL was inaccurate, the new test will produce a higher LDL number, he explained.

Along with implementing the new calculation, Quest has updated standard "flagging" of cholesterol levels, so that the cutoff points at which physicians should monitor cholesterol are up to date with modern medical guidelines and recommendations, Abate said.