Can lipoprotein subfractions replace traditional lipids in risk prediction of cardiovascular disease?

Can lipoprotein subfractions replace traditional lipids in risk prediction of cardiovascular diseaseThe possibility to quantify subfractions of lipid components has been largely improved by advances in lipidomics technology. Increasing evidence suggest that quantification of lipoprotein subfractions may provide additional information that is missing in today's evaluation of CVD risk, thus potentially leading to a better outcome.One paper has been submitted for publication exploring lipoprotein subfractions as early risk markers of myocardial infarction using data from HUNT. There seems to be important gender specific risk markers for myocardial infarction among lipoprotein subfractions, although the study was underpowered to draw definite conclusion on gender. From this study, we realized the importance of taking statin-treatment into account when considering the clinical relevance of new biomarkers. Sperstad S, Sæther J, Klevjer M, Giskeødegård G, Bathen T, Røsbjørgen R, Dalen H, Bye A Lipidomics profiling in the search for new myocardial infarction risk markers (submitted, Plos1) Another paper was published on the association between lipoprotein subfractions and cardiorespiratory fitness, one of the most important risk factors for CVD. Non-symptomatic patients seemed to have lipid profiles associated with insulin resistance, which might be the first step in the transition to CVD in participants with low aerobic fitness. Nodeland M, Klevjer M, Sæther JC, Giskeødegård G, Bathen TF, Wisløff U, Bye A. Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 Fitness study, Atherosclerosis. Another study was published on the association between plaque burden and lipoprotein subfractions. The study included 60 patients with suspected coronary atherosclerosis. They were examined and divided into three groups based on the extent of plaque formation in 14 segments of the coronary arteries, which supply the heart with blood. The total levels of triglycerides and HDL and LDL cholesterol were similar in all groups, but when we looked more closely at subfractions of the different particle types, we found differences that may be important for plaque formation. The patients with the most advanced plaques had higher levels of small and dense LDL particles, and also higher levels of cholesterol and other fatty substances within these particles. LDL cholesterol is often referred to as "the bad cholesterol", but it is probably primarily the small and dense LDL particles that can penetrate the artery wall and contribute to the calcification of the arteries. However, we also found that these differences were not present in patients using cholesterol-lowering statins. Sæther JC, Klevjer M, Giskeødegård G, Bathen T, Gigante B, Gjære S, Myhra M, Vesterbekkmo E, Wiseth R, Madssen E, Bye A. Small LDL subfractions are associated with coronary atherosclerosis despite no differences in conventional lipids, Physiological Genomics. Another study was completed, focusing on the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy. In this study, Lp(a) and HDL-4-free cholesterol showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurements of lipoprotein subfractions in patients on lipid-lowering therapy may provide additional information on lipid content in coronary atheromatous plaques compared to conventional lipid measures. Sæther JC, Vesterbekkmo E, Gigante B, Giskeødegård GF, Bathen TF, Follestad T, Wiseth R Madssen E, Bye A The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy (submitted, American Heart journal).

Can lipoprotein subfractions replace traditional lipids in risk prediction of cardiovascular diseaseThe possibility to quantify subfractions of lipid components has been largely improved by advances in lipidomics technology. Increasing evidence suggest that quantification of lipoprotein subfractions may provide additional information that is missing in today's evaluation of CVD risk, thus potentially leading to a better outcome.As risk prediction forms the basis of the National Guidelines for Individual Primary Prevention of CVD, it is extremely important to provide healthcare personnel with the most accurate risk prediction tools, as these determines all further interventions in the individual patients. With the new and improved NORRISK 2 algorithm, we are in the progress of improving CVD risk prediction in Norway. However, a large group of patients still develops severe atherosclerosis or unexpected CVD events despite being categorized at “low-risk” by the currently available risk prediction tools. In the near future, with technological progress, it is likely that new risk markers will emerge to improve the risk prediction models. In Norway, with our unique access to large population-based cohorts and well-characterized patient registries, we should make the most out of these resources, and be in front in biomarker discovery. Primary aims 1. Determine if circulating lipoprotein subfractions are associated with parameters related to atherosclerotic burden and plaque composition in the coronary arteries (WP1) Status February 2022: - One Master thesis has been delivered (Sigri Bakken Sperstad, SINTEF) exploring lipoprotein subfractions as early risk markers of myocardial infarction using data from HUNT. There seems to be important gender specific risk markers for myocardial infarction among lipoprotein subfractions. - One "hovedoppgave" thesis is delivered and published on the association between lipoprotein subfractions and cardiorespiratory fitness, one of the most important risk factors for CVD. Non-symptomatic patients seem to have lipid profiles associated with insulin resistance, which might be the first step in the transition to CVD in participants with low aerobic fitness. - One study on the association between plaque burden and lipoprotein subfractions are ready for publication during spring 2022. 2. Determine if circulating lipoprotein subfractions can add value on top of the traditional risk factors in the currently used algorithms for CVD risk (WP2) Status February 2022: - One study is at the data analysis stage, exploring the circulating lipoprotein subfractions can add value on top of the traditional risk factors in the currently used algorithms for CVD risk. Will be published autumn 2022.

Lipoprotein subfractions in CVD risk predictionThe possibility to quantify subfractions of lipid components has been largely improved by advances in lipidomics technology. Increasing evidence suggest that quantification of lipoprotein subfractions may provide additional information that is missing in today's evaluation of CVD risk, thus potentially leading to a better outcome.As risk prediction forms the basis of the National Guidelines for Individual Primary Prevention of CVD, it is extremely important to provide healthcare personnel with the most accurate risk prediction tools, as these determines all further interventions in the individual patients. With the new and improved NORRISK 2 algorithm, we are in the progress of improving CVD risk prediction in Norway. However, a large group of patients still develops severe atherosclerosis or unexpected CVD events despite being categorized at “low-risk” by the currently available risk prediction tools. In the near future, with technological progress, it is likely that new risk markers will emerge to improve the risk prediction models. In Norway, with our unique access to large population-based cohorts and well-characterized patient registries, we should make the most out of these resources, and be in front in biomarker discovery. Primary aims 1. Determine if circulating lipoprotein subfractions are associated with parameters related to atherosclerotic burden and plaque composition in the coronary arteries (WP1) Status February 2021: All results are collected, statistical analyses are performed. The only thing left is to write the discussion of the paper. 2. Determine if circulating lipoprotein subfractions can add value on top of the traditional risk factors in the currently used algorithms for CVD risk (WP2) Status February 2021: Data from HUNT and all patient registries are ordered and expected to arrive during the next couple of months. Case and controls will then be selected, and samples will be shipped for lipidomics analysis. A pilot has been run by a master student, and we are currently examining the data. There seems to be important gender specific risk markers for myocardial infarction among lipoprotein subfractions.