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Deutsches Arzteblatt International Dec 2019Hypertriglyceridemia affects 15-20% of the adult population and is associated with overweight, metabolic syndrome, and diabetes mellitus. It is often discovered... (Review)
Review
BACKGROUND
Hypertriglyceridemia affects 15-20% of the adult population and is associated with overweight, metabolic syndrome, and diabetes mellitus. It is often discovered incidentally.
METHODS
This review is based on pertinent publications retrieved by a selective literature search, including current guidelines on hypertriglyceridemia.
RESULTS
Elevated triglyceride (TG) levels are causally linked to cardiovascular disease; TG levels above 1000 mg/dL (11.4 mmol/L) can induce acute pancreatitis. The individual risk of cardiovascular disease and of pancreatitis must be estimated in order to decide whether, and how, hypertriglyceridemia should be treated. Lifestyle modifications (cessation of alcohol consumption, reduced intake of rapidly metabolized carbohydrates), weight loss, and blood sugar control are the most effective ways to lower TG levels. The need to lower the low-density lipoprotein (LDL) concentration must be determined on the basis of the cardiovascular risk, independently of the success of the lifestyle changes. Few patients need specific drug treatment to lower the TG level. Fibrates can lower TG concentrations, but their efficacy in combination with statins has not been clearly shown in endpoint studies. A daily dose of 2-4 g omega-3 fatty acids can also lower TG levels. To date, only a single large-scale randomized, blinded trial has shown the efficacy of 4 g of eicosapentaenoic acid ethyl ester per day in lowering the risk in high-risk patients (number needed to treat = 21). Patients with the very rare purely genetic types of hypertriglyceridemia (familial chylomicronemia syndrome) should be treated in specialized outpatient clinics.
CONCLUSION
Hypertriglyceridemia is causally linked to cardiovascular disease and pancreatitis. Lifestyle modifications play a paramount role in its treatment.
Topics: Cardiovascular Diseases; Humans; Hypertriglyceridemia; Pancreatitis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Reduction Behavior
PubMed: 31888796
DOI: 10.3238/arztebl.2019.0825 -
Frontiers in Endocrinology 2020Elevations in plasma triglyceride are the result of overproduction and impaired clearance of triglyceride-rich lipoproteins-very low-density lipoproteins (VLDL) and... (Review)
Review
Elevations in plasma triglyceride are the result of overproduction and impaired clearance of triglyceride-rich lipoproteins-very low-density lipoproteins (VLDL) and chylomicrons. Hypertriglyceridemia is characterized by an accumulation in the circulation of large VLDL-VLDL-and its lipolytic products, and throughout the VLDL-LDL delipidation cascade perturbations occur that give rise to increased concentrations of remnant lipoproteins and small, dense low-density lipoprotein (LDL). The elevated risk of atherosclerotic cardiovascular disease in hypertriglyceridemia is believed to result from the exposure of the artery wall to these aberrant lipoprotein species. Key regulators of the metabolism of triglyceride-rich lipoproteins have been identified and a number of these are targets for pharmacological intervention. However, a clear picture is yet to emerge as to how to relate triglyceride lowering to reduced risk of atherosclerosis.
Topics: Cardiovascular Diseases; Humans; Hypertriglyceridemia; Triglycerides
PubMed: 32477261
DOI: 10.3389/fendo.2020.00252 -
International Journal of Environmental... Dec 2022Acute and chronic pancreatitis, until recently observed incidentally in pregnancy, has occurred much more frequently in the last 2-3 decades. Particularly severe... (Review)
Review
Acute and chronic pancreatitis, until recently observed incidentally in pregnancy, has occurred much more frequently in the last 2-3 decades. Particularly severe complications for the mother and fetus may be a consequence of acute pancreatitis. Therefore, it is important to know more about the diagnostic and therapeutic possibilities of pancreatic diseases in the course of pregnancy. Epidemiology, causes, clinical characteristics, differential diagnosis, and complex management are presented in this review. Particular emphasis is on the prevention of acute pancreatitis (AP) through the proper diagnosis and treatment of cholelithiasis and hypertriglyceridemia, both before and during pregnancy. The most up-to-date reports and management strategies are presented. This publication contributes to a wide group of scientists and practitioners better understanding the discussed issues, and indicates the directions of research for the future.
Topics: Pregnancy; Female; Humans; Pancreatitis; Acute Disease; Pregnancy Complications; Hypertriglyceridemia; Cholelithiasis
PubMed: 36498253
DOI: 10.3390/ijerph192316179 -
Nutrients Dec 2022Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have... (Meta-Analysis)
Meta-Analysis Review
Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.
Topics: United States; Humans; COVID-19; Fatty Acids, Omega-3; Cardiovascular Diseases; Cholesterol, HDL; Triglycerides; Cholesterol; Hypertriglyceridemia; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Myocardial Infarction
PubMed: 36501174
DOI: 10.3390/nu14235146 -
European Heart Journal Jan 2020Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as... (Review)
Review
Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as important contributors to ASCVD while severe hypertriglyceridaemia raises risk of pancreatitis. While low-density lipoprotein is the primary treatment target for lipid lowering therapy, secondary targets that reflect the contribution of TRL such as apoB and non-HDL-C are recommended in the current guidelines. Reduction of severely elevated triglycerides is important to avert or reduce the risk of pancreatitis. Here we discuss interventions for hypertriglyceridaemia, including diet and lifestyle, established treatments such as fibrates and omega-3 fatty acid preparations and emerging therapies, including various biological agents.
Topics: Humans; Hypertriglyceridemia; Life Style; Triglycerides
PubMed: 31764986
DOI: 10.1093/eurheartj/ehz785 -
Frontiers in Endocrinology 2020Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for... (Review)
Review
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.
Topics: Disease Management; Genetic Predisposition to Disease; Humans; Hypertriglyceridemia; Triglycerides
PubMed: 32982991
DOI: 10.3389/fendo.2020.00616 -
Frontiers in Endocrinology 2020The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When... (Review)
Review
The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situation is termed the multifactorial chylomicronemia syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk.
Topics: Humans; Hyperlipoproteinemia Type I; Hypertriglyceridemia; Pancreatitis
PubMed: 33193106
DOI: 10.3389/fendo.2020.593931 -
Current Atherosclerosis Reports Sep 2021Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in... (Review)
Review
PURPOSE OF REVIEW
Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well.
RECENT FINDINGS
NHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP). Residual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.
Topics: Acute Disease; Adult; Angiopoietin-Like Protein 3; Angiopoietin-like Proteins; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypertriglyceridemia; Nutrition Surveys; Pancreatitis; Triglycerides
PubMed: 34515873
DOI: 10.1007/s11883-021-00962-z -
Molecular Metabolism Jun 2021Recent studies suggest that excess dietary fructose contributes to metabolic dysfunction by promoting insulin resistance, de novo lipogenesis (DNL), and hepatic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Recent studies suggest that excess dietary fructose contributes to metabolic dysfunction by promoting insulin resistance, de novo lipogenesis (DNL), and hepatic steatosis, thereby increasing the risk of obesity, type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), and related comorbidities. Whether this metabolic dysfunction is driven by the excess dietary calories contained in fructose or whether fructose catabolism itself is uniquely pathogenic remains controversial. We sought to test whether a small molecule inhibitor of the primary fructose metabolizing enzyme ketohexokinase (KHK) can ameliorate the metabolic effects of fructose.
METHODS
The KHK inhibitor PF-06835919 was used to block fructose metabolism in primary hepatocytes and Sprague Dawley rats fed either a high-fructose diet (30% fructose kcal/g) or a diet reflecting the average macronutrient dietary content of an American diet (AD) (7.5% fructose kcal/g). The effects of fructose consumption and KHK inhibition on hepatic steatosis, insulin resistance, and hyperlipidemia were evaluated, along with the activation of DNL and the enzymes that regulate lipid synthesis. A metabolomic analysis was performed to confirm KHK inhibition and understand metabolite changes in response to fructose metabolism in vitro and in vivo. Additionally, the effects of administering a single ascending dose of PF-06835919 on fructose metabolism markers in healthy human study participants were assessed in a randomized placebo-controlled phase 1 study.
RESULTS
Inhibition of KHK in rats prevented hyperinsulinemia and hypertriglyceridemia from fructose feeding. Supraphysiologic levels of dietary fructose were not necessary to cause metabolic dysfunction as rats fed the American diet developed hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis, which were all reversed by KHK inhibition. Reversal of the metabolic effects of fructose coincided with reductions in DNL and inactivation of the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP). We report that administering single oral doses of PF-06835919 was safe and well tolerated in healthy study participants and dose-dependently increased plasma fructose indicative of KHK inhibition.
CONCLUSIONS
Fructose consumption in rats promoted features of metabolic dysfunction seen in metabolic diseases such as T2D and NASH, including insulin resistance, hypertriglyceridemia, and hepatic steatosis, which were reversed by KHK inhibition.
Topics: Adult; Animals; Cells, Cultured; Cohort Studies; Diet, Carbohydrate Loading; Enzyme Inhibitors; Fructokinases; Fructose; Healthy Volunteers; Hepatocytes; Humans; Hypertriglyceridemia; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley; Signal Transduction; Treatment Outcome
PubMed: 33667726
DOI: 10.1016/j.molmet.2021.101196 -
Lipids in Health and Disease Oct 2022Lipid-lowering therapy is important, and the distribution of lipid levels and the incidence of hyperlipidemia may vary in different subgroups of the population. We aimed...
BACKGROUND
Lipid-lowering therapy is important, and the distribution of lipid levels and the incidence of hyperlipidemia may vary in different subgroups of the population. We aimed to explore the distribution of lipid levels and the prevalence of hyperlipidemia in subpopulations with subgroup factors, including age, sex, race, and smoking status.
METHODS
Our study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, ultimately enrolling and analyzing 15,499 participants. A cross-sectional analysis was performed to assess the distribution of lipids and prevalence of hyperlipidemia in subpopulations, and multifactorial logistic regression analyses were performed for the prevalence of hyperlipidemia, adjusted for age, sex, race and smoking status.
RESULTS
Blacks had significantly lower mean serum total cholesterol and triglycerides and higher serum high-density lipoprotein cholesterol (HDL-C) than whites (P < 0.001). In contrast, Mexican Americans had markedly higher mean serum triglycerides and lower serum HDL-C than whites (P < 0.001). Furthermore, the prevalence of hypercholesterolemia and hypertriglyceridemia was lower in blacks than in whites (P = 0.003 and P < 0.001, respectively), while the prevalence of hypertriglyceridemia was significantly higher in Mexican Americans than in whites (P = 0.002). In addition, total cholesterol and triglyceride levels were significantly higher in women aged 65 years or older and markedly higher than in men in the same age group (P < 0.001). In addition, overall mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels were higher in smokers than in nonsmokers (P = 0.01, P < 0.001, and P = 0.005, respectively).
CONCLUSION
Based on NHANES data, the mean lipid levels and prevalence of hyperlipidemia differed by sex, age, race, and smoking status.
Topics: Male; Female; Humans; Hyperlipidemias; Nutrition Surveys; Prevalence; Cross-Sectional Studies; Cholesterol, HDL; Triglycerides; Hypertriglyceridemia
PubMed: 36307819
DOI: 10.1186/s12944-022-01721-y