Lipidome Variability Within Subjects Leads to Novel Insights Into Specific Coronary Plaque Phenotypes

Posted on March 04, 2022

Fed Torta Res Spot Horizontal

Since the early 2000s, lipidomic analysis has become an increasingly hot research topic. The development of newer, better mass spectrometry technologies and standardized lipids and lipid mixtures continues to allow the lipidomics research community to get closer and closer to their goal – clinical translation of lipidomic research for the development of diagnostic and therapeutic tools. Avanti is a leader in the development of standardized lipids and lipid mixtures used in lipidomics research. We continue to develop our offerings to align with the needs of the research community. Federico Torta, a dear customer and leader in the lipidomic analysis community, recently published research linking visit-to-visit variability of certain lipid classes to the burden of coronary atherosclerosis in humans.

Why is visit-to-visit variability of lipid abundance important to study?

Natural biological variability exists for many physiological parameters. Several of these, including serum cholesterol, glucose, and blood pressure, can predict adverse cardiovascular events. Looking even deeper, circulating cholesterol and triglycerides are associated with progression of coronary atherosclerosis. Recent advances in lipidomic analysis have led to the identification of several non-sterol lipids associated with the development of atherosclerotic plaques. Since this field is relatively new, most studies have been one-dimensional and only assessed the lipidomic profile at one time point. While a great starting point, these studies overlook unique patterns of variability of lipid classes such as diacylglycerols, triacylglycerols, PE, LPE, and LPC within a 24-hour time frame. And few studies have been conducted linking the long-term variability of these lipids with early disease states. The hope that a study of this type brings is the uncovering of non-sterol lipids that may provide additional biomarkers for early onset coronary artery disease (CAD).

How Dr. Torta’s Group Addressed This Issue

This study was a huge undertaking, investigating nearly 300 plasma lipids over a 6-month period. Participants of this study were asymptomatic but at-risk of CAD and had well-controlled cardiometabolic parameters. Two variability studies were conducted: one investigated the variability of plasma lipids between subjects and the other investigated the plasma lipid variability within each subject. After conducting these studies, they narrowed their focus to plasma lipids with 1.2-fold or greater variability between-subject as compared to within-subject variability. These plasma lipids were assessed to determine their association with Framingham risk score (FRS) and volumes of plaque burden measured by computed tomography coronary angiography (CTCA).

Diacylglycerols and triacylglycerols were found to remain stable throughout a 6-month period, and it was determined that one measurement would suffice for diagnostic studies. Most of the other lipids exhibited somewhat greater variability between-subject than within-subject, exceptions being PS, PC, and sphingosine-1-phosphate species. The study showed that four sphingolipids are candidates to diagnose subclinical CAD. Another interesting point was that many participants were taking medications for type 2 diabetes or hypertension. An analysis was conducted to determine if these medications alone were contributing to increased lipid levels in participants. They found that only lysophosphatidylinositol 20:4 was increased by medications other than statins. Statins, on the other hand, altered levels of 38 lipids. The 14 participants using statins were then excluded from the analysis and the data was re-analyzed. After re-analysis of the data, only two lipids were removed due to statistical insignificance, LPE 22:6 and PC 38:6.

However, the reanalysis led to the discovery that 9 LPCs and their high visit-to-visit variability were associated with fibrotic plaque. The lipids associated with calcified plaque remained mostly the same as those found while including statin users. 5 additional lipids and their visit-to-visit variability were determined to be associated with noncalcified plaque. These findings emphasize the importance of using visit-to-visit analyses rather than data taken from a single time point. Previous studies conducted at a single time point revealed 4 ceramides and 3 PCs as risk factors for future coronary events. The study conducted by Dr. Torta and his group analyzing visit-to-visit variability showed that not only are these lipids risk factors but also their variability reveals novel insights into specific coronary plaque phenotypes.

Take the plunge and explore the lipidome!

Lipidomic analysis can reveal novel insights into disease states, therapeutic opportunities, and diagnostic biomarkers. Avanti offers several lipid standards and standardized lipid mixtures to use in your lipidomic analysis research, and we are constantly innovating to meet the needs of the lipidomics community. If you are new to the field, Avanti is hosting a webinar series focused on lipidomics research. Join us to hear three industry leaders discuss how lipidomic standardization has changed the field and opened new doors for their research. Register for the event today!

If you are already interested in getting started, click HERE to go to our lipidomics division page and find the standards you need! We are excited to be at the forefront of the lipidomics research field and can’t wait to see where it leads you!

Please take the time to read Dr. Federico Torta’s Full Research Publication published in Arteriosclerosis, Thrombosis, and Vascular Biology.

Image Credit: Original Research Publication