Learn More. Sign in via OpenAthens. Sign in via Shibboleth. AccessBiomedical Science. AccessEmergency Medicine. Case Files Collection. Clinical Sports Medicine Collection. Davis AT Collection. Davis PT Collection. Murtagh Collection. About Search. Enable Autosuggest. You have successfully created a MyAccess Profile for alertsuccessName. Both Nexlitol and Nexlizet can cause serious side effects. Your doctor can help you decide if one of these drugs would benefit your treatment plan.
Praluent alirocumab was approved by the FDA in as an add-on treatment for familial hypercholesterolemia. This is a genetic condition that causes severely high cholesterol.
Praluent was originally approved by the FDA in for treating heart disease and primary inherited hyperlipidemia. Alirocumab, the active drug in Praluent, is a monoclonal antibody.
This is a protein synthesized in a laboratory that behaves like antibodies made by the human body. Praluent comes as a liquid solution in a prefilled pen. You deliver it as an injection every 2 to 4 weeks, which can be done at home.
It has a number of reported possible side effects, so be sure to discuss with your doctor whether it would suit your treatment plan. You can make changes to your lifestyle to prevent high cholesterol or reduce your risk of developing hyperlipidemia:.
You may want to try a heart healthy eating plan like the Mediterranean diet , which includes a lot of the nutritious foods mentioned above. People with untreated hyperlipidemia have double the risk of developing coronary heart disease as those with normal-range cholesterol levels. Coronary heart disease can lead to heart attack, stroke, or other serious problems. You may be able to prevent complications and manage hyperlipidemia by making lifestyle choices, like:. If lifestyle choices are not sufficient, you can talk with your doctor about adding medications such as statins to help bring your cholesterol and triglycerides down to healthy levels.
A new study has shed light on the benefits and risks of people over 75 taking this medication. It found that older adults who stopped taking statins…. When should you start getting screened for high cholesterol? Is it always possible to manage high cholesterol with diet and exercise alone? Learn the…. New research finds that sugar-laden drinks can not only increase cholesterol levels, but reduce the amount of HDL good cholesterol in our bodies….
Your cholesterol can be tested without fasting. But for some,. Your provider may want you to take medicine for your cholesterol if lifestyle changes do not work. This will depend on:. You are more likely to need medicine to lower your cholesterol :.
There are several types of drugs to help lower blood cholesterol levels. The drugs work in different ways. Statins are one kind of drug that lowers cholesterol and has been proven to reduce the chance of heart disease. Other drugs are available if your risk is high and statins do not lower your cholesterol levels enough.
These include ezetimibe and PCSK9 inhibitors. High cholesterol levels can lead to hardening of the arteries , also called atherosclerosis.
This occurs when fat, cholesterol, and other substances build up in the walls of arteries and form hard structures called plaques. Over time, these plaques can block the arteries and cause heart disease, stroke, and other symptoms or problems throughout the body.
Disorders that are passed down through families often lead to higher cholesterol levels that are harder to control. Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia.
J Am Coll Cardiol. PMID: pubmed. Genest J, Libby P. However, as mentioned above, the inheritance does not follow a discrete Mendelian monogenic pattern. In a small minority of kindreds, the combined hyperlipidemia phenotype appears to segregate as an autosomal dominant trait often with variable penetrance , but the molecular cause remains unknown.
The reason that it clusters in families, similar to other familial HTGs, is due to the aggregation of many independent small effect polymorphisms within family units. Patients with combined hyperlipidemia have increased risk of atherosclerotic vascular disease [ 1 , 36 , 37 ]. Combined hyperlipidemia sometimes requires secondary factors for overt disease expression. These include poor diet, obesity, type 2 diabetes or hypothyroidism [ 37 ].
Combined hyperlipidemia is a polygenic trait, like most other HTG states. But in addition, combined hyperlipidemia patients also carry genetic variants or mutations that raise LDL cholesterol [ 6 , 9 , 28 ].
This complex genetic susceptibility tends to cluster in families, but because the susceptibility alleles are on different chromosomes, the susceptibility is not transmitted in a clear Mendelian manner.
The complex pattern of susceptibility alleles also explains why some family members display only certain components of the combined dyslipidemia pattern, namely isolated or some combination of high LDL cholesterol, high TG or depressed HDL cholesterol. The clustering of genetic susceptibility and secondary factors in families means that biochemical screening of family members and counselling are still indicated once an index case has been identified.
In our experience, combined hyperlipidemia patients are relatively refractory to usual treatments, and may require higher doses and combinations of lipid lowering agents, focusing on statins, which are the centerpiece of therapy for reduction of the LDL component of the phenotype.
Thus, depending on the degree of HTG, therapeutic goals vary with variation in the emphasis of non-pharmacologic and pharmacologic therapeutic strategies Table 5 , Table 6. However, non-pharmacologic interventions [ 34 ] must be optimized, since HTG is often exacerbated by modifiable factors. Dietary intervention remains the mainstay of therapy. Medium chain fatty acids can provide an alternate source of dietary fat given their direct absorption into the portal circulation with no reliance on chylomicron formation.
Given this strict dietary regimen, supplementation with essential fatty acids such as walnut oil or sunflower oil topically [ 38 ] and fat soluble vitamins must be considered. In apo C-II deficiency, plasma transfusions have been shown to have transient benefit [ 39 ]. Furthermore, there are some special situations that call for particular treatment strategies Table 6. Note that bile acid sequestrants should be avoided in patients with moderate to severe HTG due to their potential for further increasing TG levels.
But while randomized clinical trials clearly demonstrate the TG-lowering efficacy of fibrates, they have shown inconsistent impact on reduction of CVD [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].
Addition of a fibrate to statin therapy seems to provide little additional benefit in CVD risk reduction. For instance, the Action to Control Cardiovascular Risk in Diabetes ACCORD study [ 52 ] showed no additional cardiovascular benefit when adding fenofibrate to simvastatin therapy in patients with type 2 diabetes.
Other post-hoc and pre-specified sub-group analyses demonstrated cardiovascular benefit among patients with high TG levels, with or without low HDL cholesterol levels. Thus, fibrates in the high TG patient subgroup may warrant serious consideration. The exact lipid-lowering mechanism of high-dose niacin remains unknown. However, niacin remains a suitable therapeutic option for some HTG patients, especially if a statin is not indicated or if the patient is intolerant of statin treatment.
Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, resulting in increased hepatic LDL receptor expression and enhanced cholesterol clearance from plasma. In addition, statins appear to have pleiotropic effects, including anti-inflammatory, anti-thrombotic, and anti-proliferative properties that may prevent plaque growth and rupture [ 62 ]. Unlike the other therapies discussed here, statins have proven cardiovascular morbidity and mortality benefit.
Combination therapy with a statin and fibrate can help normalize several components of the lipid profile, especially in patients with HLP type 2B and 3 [ 65 , 66 ]. In combination therapy with statins, fenofibrate is preferred to other fibrates, particular gemfibrozil, which has a higher rate of rhabdomyolysis when combined with a statin [ 67 ].
Ezetimibe is an intestinal cholesterol absorption inhibitor whose primary target is the NPC1L1 intestinal cholesterol transporter. Ezetimibe might be a useful adjunct therapy in patients with HTG. For instance, patients on a combination of fenofibrate mg plus ezetimibe vs. The TG-lowering efficacy is related to baseline TG values [ 70 ]. Thus, omega-3 fatty acids remain an important option in the management of HTG. HTG is commonly encountered in clinical practice, and is a clinically relevant cause of acute pancreatitis.
Recent genetic research has elucidated the polygenic nature of most cases of HTG, although the rare monogenic forms cause severe HTG and are informative biologically and biochemically.
Non-pharmacologic therapy is recommended to all patients with TG levels exceeding normal values while the decision to commence pharmacologic therapy depends on the degree of TG elevation. Further work is required to define the benefits of treating patients with mild to moderate HTG. Hegele is supported by the Jacob J. National Center for Biotechnology Information , U. Journal List Nutrients v. Published online Mar Amanda Brahm and Robert A.
Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC.
Abstract Hypertriglyceridemia HTG is commonly encountered in lipid and cardiology clinics. Keywords: dyslipidemia, polygenic, complex trait, mutation, single nucleotide polymorphism. Introduction Hypertriglyceridemia HTG is a common clinical diagnosis, sometimes defined when plasma triglyceride TG concentration rises above a threshold value, such as the 90th or 95th percentile for age and sex.
Table 1 Hypertriglyceridemia: some proposed clinical definitions. Open in a separate window. Table 2 Classification of hypertriglyceridemia modified Fredrickson. Clinical Features of Chylomicronemia Development of physical findings in HTG is less common today that in the past, likely due to earlier diagnosis and treatment. Table 3 Genes associated with autosomal recessive familial chylomicronemia.
Table 4 Common DNA polymorphisms associated with hypertriglyceridemia. Table 5 Therapeutic goals and treatment strategies in hypertriglyceridemia. Table 6 Managing hypertriglyceridemia in special situations. LPL-based gene therapies may be helpful future. Plasma transfusions may transiently help patients with APOC2 mutations. Gemfibrozil in the 3 rd trimester in pregnancy in HLP type 1.
Apheresis is of questionable value. Acute pancreatitis with severe hypertriglyceridemia -. Secondary Factors Contributing to Polygenic HTG Secondary non-genetic factors associated with HTG are covered in depth elsewhere [ 1 ] but briefly, these include: obesity, metabolic syndrome, diet with high positive energy-intake balance and high fat or high glycemic index, alcohol consumption, diabetes mainly type 2 , renal disease uremia or glomerulonephritis , pregnancy particularly in the third trimester , paraproteinemia, systemic lupus erythematosis, and some medications, including corticosteroids, oral estrogen, tamoxifen, thiazides, non-cardioselective beta-blockers, bile acid sequestrants, cyclophosphamide, antiretroviral drugs, and second generation antipsychotic agents.
Statins Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, resulting in increased hepatic LDL receptor expression and enhanced cholesterol clearance from plasma. Ezetimibe Ezetimibe is an intestinal cholesterol absorption inhibitor whose primary target is the NPC1L1 intestinal cholesterol transporter.
Conclusions HTG is commonly encountered in clinical practice, and is a clinically relevant cause of acute pancreatitis. Acknowledgments Hegele is supported by the Jacob J.
References 1. Yuan G. Hypertriglyceridemia: Its etiology, effects and treatment. Hegele R. Plasma lipoproteins: Genetic influences and clinical implications. Johansen C. Genetic determinants of plasma triglycerides. Lipid Res. Genetic bases of hypertriglyceridemic phenotypes.
The complex genetic basis of plasma triglycerides. Allelic and phenotypic spectrum of plasma triglycerides. Berglund L. Evaluation and treatment of hypertriglyceridemia: An endocrine society clinical practice guideline. A polygenic basis for four classical Frederickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia.
Feoli-Fonseca J. Familial lipoprotein lipase deficiency in infancy: Clinical, biochemical, and molecular study. Rahalkar A. Monogenic pediatric dyslipidemias: Classification, genetics and clinical spectrum. Hall L.
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