-
Endocrine Reviews Jul 2022Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for...
Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents-especially antisense RNA and monoclonal antibodies-targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms.
Topics: Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Risk Factors; Triglycerides
PubMed: 34676866
DOI: 10.1210/endrev/bnab037 -
European Heart Journal Jan 2020
Topics: Cardiovascular Diseases; Dyslipidemias; Heart Disease Risk Factors; Humans; Lipids; Risk Factors; Triglycerides
PubMed: 31504418
DOI: 10.1093/eurheartj/ehz455 -
Molecular Metabolism Aug 2021Non-alcoholic fatty liver disease, or as recently proposed 'metabolic-associated fatty liver disease' (MAFLD), is characterized by pathological accumulation of... (Review)
Review
BACKGROUND
Non-alcoholic fatty liver disease, or as recently proposed 'metabolic-associated fatty liver disease' (MAFLD), is characterized by pathological accumulation of triglycerides and other lipids in hepatocytes. This common disease can progress from simple steatosis to steatohepatitis, and eventually end-stage liver diseases. MAFLD is closely related to disturbances in systemic energy metabolism, including insulin resistance and atherogenic dyslipidemia.
SCOPE OF REVIEW
The liver is the central organ in lipid metabolism by secreting very low density lipoproteins (VLDL) and, on the other hand, by internalizing fatty acids and lipoproteins. This review article discusses recent research addressing hepatic lipid synthesis, VLDL production, and lipoprotein internalization as well as the lipid exchange between adipose tissue and the liver in the context of MAFLD.
MAJOR CONCLUSIONS
Liver steatosis in MAFLD is triggered by excessive hepatic triglyceride synthesis utilizing fatty acids derived from white adipose tissue (WAT), de novo lipogenesis (DNL) and endocytosed remnants of triglyceride-rich lipoproteins. In consequence of high hepatic lipid content, VLDL secretion is enhanced, which is the primary cause of complex dyslipidemia typical for subjects with MAFLD. Interventions reducing VLDL secretory capacity attenuate dyslipidemia while they exacerbate MAFLD, indicating that the balance of lipid storage versus secretion in hepatocytes is a critical parameter determining disease outcome. Proof of concept studies have shown that promoting lipid storage and energy combustion in adipose tissues reduces hepatic lipid load and thus ameliorates MAFLD. Moreover, hepatocellular triglyceride synthesis from DNL and WAT-derived fatty acids can be targeted to treat MAFLD. However, more research is needed to understand how individual transporters, enzymes, and their isoforms affect steatosis and dyslipidemia in vivo, and whether these two aspects of MAFLD can be selectively treated. Processing of cholesterol-enriched lipoproteins appears less important for steatosis. It may, however, modulate inflammation and consequently MAFLD progression.
Topics: Adipose Tissue; Animals; Disease Models, Animal; Dyslipidemias; Energy Metabolism; Fatty Acids; Hepatocytes; Humans; Lipid Droplets; Lipogenesis; Lipoproteins, VLDL; Liver; Non-alcoholic Fatty Liver Disease; Severity of Illness Index
PubMed: 33892169
DOI: 10.1016/j.molmet.2021.101238 -
Molecular Metabolism Dec 2020Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a global health problem. Cardiovascular diseases (CVD) are the most common cause of mortality in NAFLD... (Review)
Review
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a global health problem. Cardiovascular diseases (CVD) are the most common cause of mortality in NAFLD patients. NAFLD and CVD share several common risk factors including obesity, insulin resistance, and type 2 diabetes (T2D). Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense low-density lipoprotein (LDL) particles, and decreased high-density lipoprotein cholesterol (HDL-C) levels, is often observed in NAFLD patients.
SCOPE OF REVIEW
In this review, we highlight recent epidemiological studies evaluating the link between NAFLD and CVD risk. We further focus on recent mechanistic insights into the links between NAFLD and altered lipoprotein metabolism. We also discuss current therapeutic strategies for NAFLD and their potential impact on NAFLD-associated CVD risk.
MAJOR CONCLUSIONS
Alterations in hepatic lipid and lipoprotein metabolism are major contributing factors to the increased CVD risk in NAFLD patients, and many promising NASH therapies in development also improve dyslipidemia in clinical trials.
Topics: Cardiovascular Diseases; Dyslipidemias; Humans; Lipid Metabolism; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Risk Factors
PubMed: 33010471
DOI: 10.1016/j.molmet.2020.101092 -
Atherosclerosis Nov 2019
Review
Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Consensus; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Lipids; Male; Middle Aged; Risk Assessment; Risk Factors; Risk Reduction Behavior; Treatment Outcome
PubMed: 31591002
DOI: 10.1016/j.atherosclerosis.2019.08.014 -
Nutrients Sep 2020Convincing evidence supports the intake of specific food components, food groups, or whole dietary patterns to positively influence dyslipidemia and to lower risk of... (Review)
Review
Convincing evidence supports the intake of specific food components, food groups, or whole dietary patterns to positively influence dyslipidemia and to lower risk of cardiovascular diseases (CVD). Specific macro- and micro-components of a predominantly plant-based dietary pattern are vegetable fats, dietary fibers, and phytonutrients such as phytosterols. This review summarizes the current knowledge regarding effects of these components on lowering blood lipids, i.e., low-density lipoprotein cholesterol (LDL-C) and on reducing CVD risk. The beneficial role of a plant-based diet on cardiovascular (CV) health has increasingly been recognized. Plant-based dietary patterns include a Mediterranean and Nordic diet pattern, the dietary approaches to stop hypertension (DASH), and Portfolio diet, as well as vegetarian- or vegan-type diet patterns. These diets have all been found to lower CVD-related risk factors like blood LDL-C, and observational study evidence supports their role in lowering CVD risk. These diet patterns are not only beneficial for dyslipidemia management and prevention of CVD but further contribute to reducing the impact of food choices on environmental degradation. Hence, the CV health benefits of a predominantly plant-based diet as a healthy and environmentally sustainable eating pattern are today recommended by many food-based dietary as well as clinical practice guidelines.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Diet, Healthy; Diet, Vegetarian; Dyslipidemias; Heart Disease Risk Factors; Humans
PubMed: 32883047
DOI: 10.3390/nu12092671 -
High Blood Pressure & Cardiovascular... May 2022Treating blood pressure (BP) alone may provide only limited benefits while it is recommendable to manage the total cardiovascular risk. To date, several studies have... (Review)
Review
Treating blood pressure (BP) alone may provide only limited benefits while it is recommendable to manage the total cardiovascular risk. To date, several studies have shown that concomitant treatment of hypertension and dyslipidemia with non-pharmacological approaches and/or metabolically neutral antihypertensive drugs and statins produce a significantly greater reduction of the risk of developing cardiovascular disease. Thus, in this review article, we summarize the available evidence regarding non-pharmacological and pharmacological approaches with a favourable effect on both BP and lipids.
Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Dyslipidemias; Humans; Hypertension
PubMed: 35334087
DOI: 10.1007/s40292-022-00507-8 -
Clinica E Investigacion En... May 2021
Topics: Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 33966806
DOI: 10.1016/j.arteri.2021.02.003 -
Atherosclerosis Jul 2021Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations... (Review)
Review
Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.
Topics: Apolipoproteins E; Dyslipidemias; Humans; Hyperlipoproteinemia Type II; Proprotein Convertase 9; Receptors, LDL
PubMed: 34058468
DOI: 10.1016/j.atherosclerosis.2021.05.007 -
Nutrients Sep 2021The progression of chronic kidney disease (CKD) leads to altered lipid metabolism. CKD patients exhibit high blood triglyceride (TG) levels, reduced concentrations and... (Review)
Review
The progression of chronic kidney disease (CKD) leads to altered lipid metabolism. CKD patients exhibit high blood triglyceride (TG) levels, reduced concentrations and functionality of high-density lipoproteins (HDL), and elevated levels of atherogenic small, dense, low-density lipoproteins (sdLDL). Disorders of lipid metabolism and other metabolic disturbances place CKD patients at high risk for cardiovascular disease (CVD). Extensive evidence supports the cardioprotective effects of unsaturated fatty acids, including their beneficial effect on serum cholesterol and TG levels. Dietary lipids might therefore be especially important in the nutritional management of CKD. We review current dietary recommendations for fat intake by CKD patients and suggest potential nutritional interventions by emphasizing dietary lipids that might improve the blood lipid profile and reduce cardiovascular risk in CKD.
Topics: Dyslipidemias; Humans; Lipids; Renal Insufficiency, Chronic
PubMed: 34579015
DOI: 10.3390/nu13093138