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New Therapies for Lowering Triglyceride-Rich Lipoproteins: JACC Focus Seminar 3/4.
Rosenson, RS, Shaik, A, Song, W
Journal of the American College of Cardiology. 2021;(18):1817-1830
Abstract
Emerging evidence suggests that elevated concentrations of triglyceride-rich lipoprotein remnants (TRLs) derived from hepatic and intestinal sources contribute to the risk of atherosclerotic cardiovascular events. Natural selection studies support a causal role for elevated concentrations of remnant cholesterol and the pathways contributing to perturbations in metabolic pathways regulating TRLs with an increased risk of atherosclerotic cardiovascular disease events. New therapies targeting select catalytic pathways in TRL metabolism reduce atherosclerosis in experimental models, and concentrations of TRLs in patients with a vast range of triglyceride levels. Clinical trials with inhibitors of angiopoietin-like 3 protein and apolipoprotein C-III will be required to provide further guidance on the potential contribution of these emerging therapies in the paradigm of cardiovascular risk management in patients with elevated remnant cholesterol.
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Fasting, non-fasting and postprandial triglycerides for screening cardiometabolic risk.
Keirns, BH, Sciarrillo, CM, Koemel, NA, Emerson, SR
Journal of nutritional science. 2021;:e75
Abstract
Fasting triacylglycerols have long been associated with cardiovascular disease (CVD) and other cardiometabolic conditions. Evidence suggests that non-fasting triglycerides (i.e. measured within 8 h of eating) better predict CVD than fasting triglycerides, which has led several organisations to recommend non-fasting lipid panels as the new clinical standard. However, unstandardised assessment protocols associated with non-fasting triglyceride measurement may lead to misclassification, with at-risk individuals being overlooked. A third type of triglyceride assessment, postprandial testing, is more controlled, yet historically has been difficult to implement due to the time and effort required to execute it. Here, we review differences in assessment, the underlying physiology and the pathophysiological relevance of elevated fasting, non-fasting and postprandial triglycerides. We also present data suggesting that there may be a distinct advantage of postprandial triglycerides, even over non-fasting triglycerides, for early detection of CVD risk and offer suggestions to make postprandial protocols more clinically feasible.
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Changes in serum lipid levels during pregnancy in women with gestational diabetes. A narrative review.
Cibickova, L, Schovanek, J, Karasek, D
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2021;(1):8-12
Abstract
We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.
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4.
Triglyceride-Rich Lipoproteins and Their Remnants as Silent Promoters of Atherosclerotic Cardiovascular Disease and Other Metabolic Disorders: A Review.
Sascău, R, Clement, A, Radu, R, Prisacariu, C, Stătescu, C
Nutrients. 2021;(6)
Abstract
While targeting elevated serum levels of low-density lipoprotein cholesterol has been the mainstay of atherosclerosis prevention and treatment for decades, the evidence regarding the atherogenic role of hypertriglyceridemia is still controversial. Various epidemiological population-based studies on statin-treated subjects nominated triglycerides, triglyceride-rich lipoproteins (namely, chylomicrons and very-low-density lipoprotein particles), and their remnants as major determinants of the substantial residual cardiovascular risk. With the triglyceride-glucose index and triglyceride to high-density lipoprotein ratio emerging as surrogate indicators of peripheral artery disease and atherosclerotic cerebrovascular disease, one can conclude that further research addressing the intricate relationship between triglycerides and atherosclerosis is warranted. Therefore, this review aims to provide insight into the current clinical and epidemiological state of knowledge on the relationship between triglycerides and atherosclerotic cardiovascular disease. It also intends to highlight the connection between triglycerides and other metabolic disorders, including diabetes mellitus, and the potential benefits of triglyceride-lowering agents on cardiovascular outcomes and all-cause mortality.
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The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans.
Borén, J, Packard, CJ, Taskinen, MR
Frontiers in endocrinology. 2020;:474
Abstract
Cardiovascular disease (CVD) is the leading cause of death globally. It is well-established based on evidence accrued during the last three decades that high plasma concentrations of cholesterol-rich atherogenic lipoproteins are causatively linked to CVD, and that lowering these reduces atherosclerotic cardiovascular events in humans (1-9). Historically, most attention has been on low-density lipoproteins (LDL) since these are the most abundant atherogenic lipoproteins in the circulation, and thus the main carrier of cholesterol into the artery wall. However, with the rise of obesity and insulin resistance in many populations, there is increasing interest in the role of triglyceride-rich lipoproteins (TRLs) and their metabolic remnants, with accumulating evidence showing they too are causatively linked to CVD. Plasma triglyceride, measured either in the fasting or non-fasting state, is a useful index of the abundance of TRLs and recent research into the biology and genetics of triglyceride heritability has provided new insight into the causal relationship of TRLs with CVD. Of the genetic factors known to influence plasma triglyceride levels variation in APOC3- the gene for apolipoprotein (apo) C-III - has emerged as being particularly important as a regulator of triglyceride transport and a novel therapeutic target to reduce dyslipidaemia and CVD risk (10).
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Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy.
Santos-Baez, LS, Ginsberg, HN
Frontiers in endocrinology. 2020;:616
Abstract
Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.
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Progress in the seasonal variations of blood lipids: a mini-review.
Ma, X, Yan, H, Zhang, H, Wang, M, Zhang, Q, Zhou, X
Lipids in health and disease. 2020;(1):108
Abstract
The seasonal variations of blood lipids have recently gained increasing interest in this field of lipid metabolism. Elucidating the seasonal patterns of blood lipids is particularly helpful for the prevention and treatment of cardiovascular and cerebrovascular diseases. However, the previous results remain controversial and the underlying mechanisms are still unclear. This mini-review is focused on summarizing the literature relevant to the seasonal variability of blood lipid parameters, as well as on discussing its significance in clinical diagnoses and management decisions.
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2018 Guidelines for the management of dyslipidemia.
Rhee, EJ, Kim, HC, Kim, JH, Lee, EY, Kim, BJ, Kim, EM, Song, Y, Lim, JH, Kim, HJ, Choi, S, et al
The Korean journal of internal medicine. 2019;(4):723-771
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9.
Current Role of Lipoprotein Apheresis.
Thompson, G, Parhofer, KG
Current atherosclerosis reports. 2019;(7):26
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Abstract
PURPOSE OF REVIEW Lipoprotein apheresis is a very efficient but time-consuming and expensive method of lowering levels of low-density lipoprotein cholesterol, lipoprotein(a)) and other apoB containing lipoproteins, including triglyceride-rich lipoproteins. First introduced almost 45 years ago, it has long been a therapy of "last resort" for dyslipidaemias that cannot otherwise be managed. In recent years new, very potent lipid-lowering drugs have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current setting. RECENT FINDINGS Lipoprotein apheresis still plays an important role in managing patients with homozygous FH and some patients with other forms of hypercholesterolaemia and cardiovascular disease. In particular, patients not achieving treatment goals despite modern lipid-lowering drugs, either because these are not tolerated or the response is insufficient. Recently, lipoprotein(a) has emerged as an important cardiovascular risk factor and lipoprotein apheresis has been used to decrease lipoprotein(a) concentrations in patients with marked elevations and cardiovascular disease. However, there is considerable heterogeneity concerning the recommendations by scientific bodies as to which patient groups should be treated with lipoprotein apheresis. Lipoprotein apheresis remains an important tool for the management of patients with severe drug-resistant dyslipidaemias, especially those with homozygous FH.
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Postprandial Hypertriglyceridaemia Revisited in the Era of Non-fasting Lipid Profiles: Executive Summary of a 2019 Expert Panel Statement.
Kolovou, GD, Watts, GF, Mikhailidis, DP, Pérez-Martínez, P, Mora, S, Bilianou, H, Panotopoulos, G, Katsiki, N, Ooi, TC, Lopez-Miranda, J, et al
Current vascular pharmacology. 2019;(5):538-540