The Case Against LDL and HDL Cholesterol Testing is Building

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id="div-gpt-ad-1538580975263-4"> </div> </div></div> </div> <div class="col-lg-8"> <div id="Contentplaceholder1_TF50A5014001_Col01" class="sf_colsIn pad-lr" data-sf-element="Column 2" data-placeholder-label="Column 2"> <div > <div class="sf-Long-text" ><h1 class="page-Title">Latest News</h1></div> </div><div > <h3> <span >The Case Against LDL and HDL Cholesterol Testing is Building</span> </h3>  <div class="AdIMUInside"> <div id="div-gpt-ad-1538580975263-23" class="text-center home-spacing"></div> </div>  <div class="NewsArticle"> <div ><div><p paraid="2030349896" paraeid="{1d94c409-8660-43a4-ba7e-2654c8468f6a}{185}"><b>By Deborah Borfitz </b></p></div><div><p paraid="1158775879" paraeid="{1d94c409-8660-43a4-ba7e-2654c8468f6a}{195}"><b>October 31, 2024</b> | In another few years, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) analytes may be “obsolete” because the famously bad and good guys in standard cholesterol tests provide less useful information about heart health than other lipid molecules circulating in the blood. The evidence emerges from a recent study in children and adolescents with overweight or obesity finding a new relationship between lipids and diseases impacting metabolism, according to Cristina Legido-Quigley, Ph.D., a group leader in systems medicine at King’s College London and head of systems medicine at the Steno Diabetes Centre, a Copenhagen-based hospital.  </p></div><div><p paraid="305782529" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{28}">Using mass spectrometry-based lipidomics enabling the analysis of hundreds of lipids at a time, researchers identified a handful of fats that contribute to cardiometabolic risk but were associated with more than a child’s weight, Legido-Quigley says. Obesity clearly continues to be a determinant of fatty liver disease (hepatic steatosis), but “it might be more important to know the molecular lipids in circulation rather than having to look at the weight of the child,” she adds. “The BMI [body mass index] measure doesn’t even work in adults.” </p></div><div><p paraid="1107184594" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{38}">In the latest study, published in <i>Nature Medicine</i> (<a href="https://doi.org/10.1038/s41591-024-03279-x" target="_blank" rel="noreferrer noopener">DOI: 10.1038/s41591-024-03279-x</a>), Legido-Quigley and her colleagues report an increase in ceramides (Cers), and a decrease in lysophospholipids and omega-3 fatty acids, with obesity metabolism. Cers, phosphatidylethanolamines (PEs) and phosphatidylinositols (PIs) were also associated with insulin resistance and cardiometabolic risk, while sphingomyelins (SMs) had inverse associations. Moreover, machine learning was used to reveal a panel of three lipids—Cers, PEs, and PIs—which predicts fatty liver disease on par with liver enzymes. </p></div><div><p paraid="264151914" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{131}">Sphingomyelins were significantly decreased across all established measures of cardiometabolic diseases, including insulin resistance—a marker of prediabetes, Legido-Quigley notes. Interestingly, SMs are also quite important in cognition, being a key component of white matter serving as a communication highway within the brain. </p></div><div><p paraid="1844866007" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{152}">This was the first time lipids correlated with diabetes in children was formally studied, she says, so there was a lot of unknowns from the start. Lipidology studies in adults have found that obese people have lower levels of omega-3 fatty acids than people of a healthy weight, and the shortage may also play a role in the development of diabetes. It was therefore easy to explain the finding that children with obesity also have less of those fatty acids available. </p></div><div><p paraid="1224451909" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{166}">Ceramides represent a lesser-known family of lipids that in adults are predictive of cardiovascular events five years out, says Legido-Quigley. Researchers elsewhere, including the Mayo and Cleveland clinics in the U.S., are actively forwarding the idea of measuring ceramide concentrations in human plasma for this and a variety of other clinical applications. To that end, a large, inter-laboratory and cross-platform trial just published in <i>Nature Communications</i> (<a href="https://doi.org/10.1038/s41467-024-52087-x" target="_blank" rel="noreferrer noopener">DOI: 10.1038/s41467-024-52087-x</a>) where shared reference materials were used to correct for quantitative biases and to help harmonize lipidomics. </p></div><div><p paraid="390866444" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{199}">It remains to be learned whether ceramides are increased as much with obesity metabolism in younger people as they are in adults. Moving forward, it may also be possible to explore the idea of treating fatty liver disease by getting SMs back to healthy concentrations through diet or pharmacological means. In the recent lipidomic analysis on overweight or obese children and adolescents, eight SMs were associated with a lower prevalence of fatty liver disease as well as dyslipidemia and insulin resistance. </p></div><div><p paraid="1962182518" paraeid="{9dea7ad3-bea5-4095-9333-5de62d56758b}{245}">Fatty liver disease is a common disorder in children that’s strongly linked to obesity. Over 30% of overweight and obesity study participants were burdened with the condition, which is difficult to detect because it is typically asymptomatic, says Legido-Quigley.  </p></div><div><p paraid="360100277" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{20}">Traditional lipids still move in relation to weight—e.g., the overweight/obesity group exhibited elevated levels of the “bad” LDL cholesterol type and weight loss led to a notably high reduction in triglycerides, she adds. It’s just that the picture for heart disease risk is considerably more complex than one or two nuanced metrics. “[Lipid profiling] will provide more precise information about the levels of ceramides ... and other lipids [in the blood] that are beneficial for patients.”  </p></div><div><p paraid="1802104027" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{52}">The genetic makeup of children is also going to have a bearing on heart health, irrespective of lifestyle interventions like weight loss and more exercise, says Legido-Quigley. “It could be that some of the genes making sphingomyelin are somehow impacted. We don’t know yet.”  </p></div><div><p paraid="1611914975" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{70}"><b>Big Data Technique</b></p></div><div><p paraid="390433623" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{80}">In the relatively new and rapidly growing field of systems medicine, creating personalized treatments for patients is an everyday endeavor, Legido-Quigley says. It’s an interdisciplinary field that uses a mix of molecular data types—lipidomics as well as genomics, proteomics, metabolomics, and transcriptomics—and analyzes thousands if not millions of data points in one go using big data techniques. Her lab applies these methods to answer clinical questions about metabolic diseases as well as neurodegenerative conditions such as Alzheimer’s. </p></div><div><p paraid="471683161" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{122}">The rising global prevalence of obesity in children and adolescents is particularly concerning, with the number of affected individuals expected to be over 250 million by 2030, she reports. For the latest study, the analyzed population consisted of 1,331 children and adolescents from the HOLBAEK study in Denmark, 186 of whom opted into a comprehensive, nonpharmacological obesity management program with follow-up visits at an obesity clinic at Holbaek Hospital. </p></div><div><p paraid="1004290023" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{158}">Plasma lipidomics and deep clinical phenotyping were performed on participants from the HOLBAEK study. The study also included two large, deeply phenotyped cohorts of children and adolescents recruited from schools across Zealand, Denmark, for a population-based study. </p></div><div><p paraid="527366550" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{186}">Lipid profiling was done using mass spectrometry equipment already installed at hospitals, says Legido-Quigley, which is used to screen for inherited metabolic disorders in babies via a heel prick test. The holdup in repurposing mass spectrometry in this way has been the time-intensive work of creating “pure compounds” to define each of the lipid species to ensure they are accurately identified and quantified.  </p></div><div><p paraid="353024470" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{208}">The obesity clinic cohort provided an opportunity to get readings after the lifestyle intervention, providing tangible evidence of its effectiveness in terms of decreased counts of lipids tied to diabetes risk, insulin resistance, and blood pressure despite limited improvements in some children’s BMI, she says. The program offers holistic treatment that includes parental education, an assortment of supportive apps (e.g., nutrition, physical activity and screen time, motivational messages), and psychological support for the children.   </p></div><div><p paraid="358651388" paraeid="{7e8ef202-509f-4cac-bc57-ea4c434c4b80}{250}"><b>View to the Clinic</b></p></div><div><p paraid="1061619916" paraeid="{33c62679-33d0-4744-acc6-ba35057a46b3}{5}">For any type of lipid profiling test to be adopted in the clinic, it needs to be well designed and quantitative, Legido-Quigley. The method employed for the latest investigation with the children was only “semi-quantitative.”  </p></div><div><p paraid="15433973" paraeid="{33c62679-33d0-4744-acc6-ba35057a46b3}{35}">Legido-Quigley and her team have more recently refined their method for measuring the concentrations of various lipids to improve the accuracy of the laboratory-developed test, she shares.  In Steno Diabetes Centre, they implemented the approach by their collaborators in the Baker Heart and Diabetes Institute in Australia and are working with them in lipidomics data harmonization, which remains challenging even with quantitative methods.  </p></div><div><p paraid="1739720782" paraeid="{33c62679-33d0-4744-acc6-ba35057a46b3}{85}">She says she expects her lab’s test, which covers 700 lipids, will “very soon” become a commercially available diagnostic in the United States, albeit one without a reimbursement code. Major health insurers still consider the plasma ceramide testing for assessing cardiovascular risk experimental, investigational, or unproven, saying their clinical value has not been adequately established. </p></div><div><p paraid="1803176675" paraeid="{33c62679-33d0-4744-acc6-ba35057a46b3}{121}">Among the next steps for Legido-Quigley and her colleagues are looking at lipids found in the microbiome of the 1,331 children and adolescents from the HOLBAEK study to learn how they might be impacting obesity or gut health, based on a comparison of what is seen in the “average” microbiome. The investigators are also interested in learning if levels of ceramides seen in the blood of obese/overweight youngsters are as elevated as what has been described in adults—and perhaps shedding some new light on the role of sphingomyelins in the development of cardiometabolic disease across ages.  </p></div></div> <div id="trendmd-suggestions"></div> </div> <div id="comments-aaf37299-64e0-4030-8249-0d7368385d95_en" data-sf-role="comments-wrapper" class="sf-Comments"> <input type="hidden" data-sf-role="comments-settings" value="{"commentsThreadKey":"aaf37299-64e0-4030-8249-0d7368385d95_en","commentsThreadType":"Telerik.Sitefinity.News.Model.NewsItem","rootUrl":"/RestApi/comments-api/","isUserAuthenticatedUrl":"/RestApi/session/is-authenticated","commentsPerPage":50,"commentsTextMaxLength":100,"commentsAllowSubscription":false,"requiresCaptcha":false,"requiresAuthentication":false,"requiresApproval":false,"commentsAutoRefresh":false,"commentsRefreshInterval":3000,"commentsInitiallySortedDescending":true,"userAvatarImageUrl":"/SFRes/images/Telerik.Sitefinity.Resources/Images.DefaultPhoto.png","userDisplayName":"","isDesignMode":false,"commentsThread":{"key":"aaf37299-64e0-4030-8249-0d7368385d95_en","type":"Telerik.Sitefinity.News.Model.NewsItem","behavior":null,"commentsCount":0,"title":"The Case Against LDL and HDL Cholesterol Testing is Building","language":"en","isClosed":false,"groupKey":"Telerik.Sitefinity.Modules.News.NewsManager_newsProvider3","dataSource":"newsProvider3","author":{"key":"00000000-0000-0000-0000-000000000000","name":null,"email":null},"dateCreated":"0001-01-01T00:00:00","averageRating":null},"useReviews":false,"hasUserAlreadyReviewedUrl":"/RestApi/reviews-api","createCommentUrl":"/RestApi/reviews-api","alwaysUseUtc":false}" /> <input type="hidden" data-sf-role="comments-resources" value="{"readFullComment":"Read full comment","commentSingular":"comment","commentsPlural":"comments","subscribeLink":"Subscribe","unsubscribeLink":"Unsubscribe","subscribeToNewComments":"Subscribe to new comments","youAreSubscribedToNewComments":"You are subscribed to new comments","successfullySubscribedToNewComments":"You are successfully subscribed to new comments","successfullyUnsubscribedFromNewComments":"You are successfully unsubscribed","messageIsRequired":"Message is required!","nameIsRequired":"Author name is required!","invalidEmailFormat":"Invalid email format!","ratingIsRequired":"Rating is required!","readFullReview":"Read full review","reviewSingular":"review","reviewPlural":"reviews","subscribeToNewReviews":"Subscribe to new reviews","youAreSubscribedToNewReviews":"You are subscribed to new reviews","successfullySubscribedToNewReviews":"You are successfully subscribed to new reviews","thankYouReviewSubmited":"Thank you! 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The Case Against LDL and HDL Cholesterol Testing is Building