CLN - Feature
It is crucial to catch atherosclerotic cardiovascular disease (ASCVD) early, as it can lead to severe complications and death and is a leading cause of morbidity and mortality worldwide. The standard approach to identifying individuals at high risk for developing ASCVD who may benefit from therapy is to measure their blood lipids and lipoproteins using a lipid panel.
However, the test has suffered from a lack of standardization, which consequently leads to variability in the way results are reported. And advances in lipid testing in recent years have led to some standard practices becoming dated. To address this heterogeneity, a group of experts from the Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC), along with a physician who specializes in lipids research, developed a guidance document that aims to consolidate all the available best-practice recommendations on lipid testing.
“There are piecemeal recommendations in different documents, textbooks, or even clinical guidelines that touch on laboratory testing for lipids,” said Leslie Donato, PhD, DABCC, the co-lead author of the guidance document and assistant professor in the department of laboratory medicine and pathology at Mayo Clinic in Rochester, Minnesota. “But there’s no overarching one-stop-shop for how we test and report lipids.” The guidance document is her and her co-authors’ attempt to meet that need — and to bridge the gap between the physicians interpreting the test results and the laboratory professionals who run the testing.
Joe El-Khoury, PhD, DABCC, FADLM, a co-author of the guidance and associate professor of laboratory medicine at Yale School of Medicine, discovered from going to conferences and organizing roundtables that every lab he talked to was doing something different when it came to testing. “There needed to be a conversation about what the best practices are instead of everybody doing their own thing,” he said, “and getting a group of experts together to address this issue was, I felt, the priority for this field.”
One of the major recommendations in the new guidance is that a lipid panel should always have three measures: total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Two other biomarkers are often included: low-density lipoprotein cholesterol (LDL-C) and non-HDL-C. However, “many labs still do not report non-HDL-C,” El-Khoury said.
Beyond the classic lipid panel, the new guidance recommends testing for other biomarkers such as lipoprotein(a), also called Lp(a). The guidelines recommend testing Lp(a) in patients who have premature atherosclerosis, patients who have a family history of premature atherosclerosis as well as elevated Lp(a), with very high LDL-C levels or familial hypercholesterolemia, and finally in individuals at very high risk of ASCVD. Canadian and European guidelines recommend population-wide screening for Lp(a), meaning that Lp(a) should be checked at least once in everybody as Lp(a) concentrations are genetically determined. Lp(a) has historically flown under the radar, Donato said, but ongoing clinical trials for new medication for high expressors of Lp(a) mean that testing for the marker is going to “expand dramatically,” she said.
The guideline also makes the recommendation to test for the lipoprotein apolipoprotein B (apoB), which is a structural protein of low-density lipoproteins. A growing body of research has found that apoB can be a better and more reliable assessment of atherosclerosis risk than testing simply for LDL-C, particularly when apoB and LDL-C levels disagree.
The ADLM guidance also focused on how LDL-C levels are calculated. The most common way of calculating LDL-C for decades has been the Friedewald equation, which states: LDL-C = [Total Cholesterol] – [HDL-C] – [Triglycerides/5]. “People have used it for a long time, and no one has thought this needed any changing,” El-Khoury said. However, the equation has certain limitations, such as lowered accuracy with very low LDL-C levels as well as with high triglyceride levels.
It also requires a fasting sample. “It’s an imperfect calculation,” Donato said. “And there are just better methods.” In its place, the guideline recommends two alternative equations: one called the Martin equation, and the other one called the Sampson equation, both of which are more modern and accurate.
Another new change that the authors recommend has to do with the way that patients prepare for the test. Traditionally, patients have had to fast before a lipid panel because measuring lipids on fasting samples was considered the most surefire way of getting an accurate reading. “It’s an ingrained dogma that everyone thinks you have to be fasting to have a lipid panel drawn,” Donato said. However, more recent research has shown that “you don’t really need to do that for everybody,” El-Khoury said, and that the alterations to triglycerides due to breaking the fast turn out to be negligible for most. And eliminating the need for patients to fast would offer various advantages.
Fasting is inconvenient for older patients and patients who are dependent on medication already, and eliminating it would enable patients to take tests throughout the day rather than in the morning. But it’s crucial that laboratories make clear in reports whether results are based on a fasting or a nonfasting example.
In total, the guidance provides nineteen recommendations aimed at both the clinical community and the laboratory professional community when it comes to lipid testing.
The biggest issue at stake with different labs using different approaches, El-Khoury said, is the risk of misdiagnosing patients, and starting them on statin therapy too early or late. “As far as I know, this would be the first laboratory-organization based guideline that is pushing and emphasizing the need for labs to lead this change, and implement these things that are well under their control,” El-Khoury said.
“What we tried to do in the document is really tie it to clinical guidelines and clinical practice, so that it's easy to understand why what we're doing in the laboratory can then be translated to the clinical setting,” Donato said. Clinical guidelines are really geared toward physicians and how to interpret results — but they really don't specify how the physician gets those results.
El-Khoury acknowledged that some laboratories may not have the resources to implement all the changes recommended in the guideline. But he emphasized that lab professionals cannot make these changes alone: “We cannot work in a silo and start making changes to these things without working with our clinical colleagues,” he said. The transition will also take some education, Donato said. “We just have to figure out how to implement these changes and make sure everyone is aware of the change and educated on how to use the testing after the change is made.”
“This is now the home for anything related to lipid testing,” El-Khoury said. “We hope that the guideline will serve as a guidance for change and updating our practices so that we're all essentially doing as close as possible to the same thing when it comes to these tests.”
Grace Browne is a freelance journalist who lives in London. She currently has a fellowship funded by the International Center for Journalists through the Health Innovation call. +Email: [email protected]