Hypertriglyceridemia | |
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Other names | Elevated levels of triglycerides |
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Blood samples of a young patient with extreme hypertriglyceridemia | |
Specialty | Endocrinology |
Complications | Heart disease, pancreatitis |
Risk factors | Metabolic dysfunction-associated steatotic liver disease, atherosclerosis, alcoholism, metabolic syndrome |
Differential diagnosis | Hyperlipidemia, atheroma, hypercholesterolemia, hypercalcemia |
Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and high triglyceride levels are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels) and predispose to cardiovascular disease.
Chronically elevated serum triglyceride levels are a component of metabolic syndrome and metabolic dysfunction-associated steatotic liver disease, both of which typically involve obesity and contribute significantly to cardiovascular mortality in industrialised countries as of 2021. Extreme triglyceride levels also increase the risk of acute pancreatitis.
Hypertriglyceridemia itself is usually symptomless, although high levels may be associated with skin lesions known as xanthomas . [1]
Most people with elevated triglycerides experience no symptoms. Some forms of primary hypertriglyceridemia can lead to specific symptoms: both familial chylomicronemia and primary mixed hyperlipidemia include skin symptoms (eruptive xanthoma), eye abnormalities (lipemia retinalis), hepatosplenomegaly (enlargement of the liver and spleen), and neurological symptoms. Some experience attacks of abdominal pain that may be mild episodes of pancreatitis. Eruptive xanthomas are 2–5 mm papules, often with a red ring around them, that occur in clusters on the skin of the trunk, buttocks and extremities. [2] Familial dysbetalipoproteinemia causes larger, tuberous xanthomas; these are red or orange and occur on the elbows and knees. Palmar crease xanthomas may also occur. [1] [2]
The diagnosis is made on blood tests, often performed as part of screening. Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders ("secondary hypertriglyceridemia") or whether no such underlying cause exists ("primary hypertriglyceridemia"). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia. [1]
Acute pancreatitis may occur in people whose triglyceride levels are above 1000 mg/dL (11.3 mmol/L). [1] [2] [3] Hypertriglyceridemia is associated with 1–4% of all cases of pancreatitis. The symptoms are similar to pancreatitis secondary to other causes, although the presence of xanthomas or risk factors for hypertriglyceridemia may offer clues. [3]
The diagnosis is made on blood tests, often performed as part of screening. The normal triglyceride level is less than 150 mg/dL (1.7 mmol/L). [1] [5] Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders ("secondary hypertriglyceridemia") or whether no such underlying cause exists ("primary hypertriglyceridaemia"). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia. [1]
The National Cholesterol Education Program has set guidelines for triglyceride levels: [7] [8]
Level | Interpretation | |
---|---|---|
(mg/dL) | (mmol/L) | |
< 150 | < 1.70 | Normal range – low risk |
150–199 | 1.70–2.25 | Slightly above normal |
200–499 | 2.26–5.65 | Some risk |
500 or higher | > 5.65 | Very high – high risk |
These levels are tested after fasting 8 to 12 hours. Triglyceride levels remain temporarily higher for a period after eating.
The AHA recommends an optimal triglyceride level of 100 mg/dL (1.1 mmol/L) or lower to improve heart health. [9]
In 2016, the United States Preventive Services Task Force concluded that testing the general population under the age of 40 without symptoms is of unclear benefit. [10] [11]
Lifestyle changes including weight loss, exercise and dietary modification may improve hypertriglyceridemia. [12] [1] [13] [14] This may include dietary changes such as restriction of fat and carbohydrates (specifically fructose [13] [15] and sugar-sweetened beverages [1] ) and increased consumption of omega-3 fatty acids from algae, nuts, and seeds. [16] [17]
The decision to treat hypertriglyceridemia with medication depends on the levels and on the presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate class. Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main drug treatment for moderate hypertriglyceridemia where reduction of cardiovascular risk is required. [1] Medications are recommended in those with high levels of triglycerides that are not corrected with lifestyle modifications, with fibrates being recommended first. [1] [18] [19] Epanova (omega-3-carboxylic acids) is another prescription drug used to treat very high levels of blood triglycerides. [20]
As of 2006, the prevalence of hypertriglyceridemia in the United States was 30%. [5]
Analysis of the genes in depression and anxiety showed those linked solely to depression were also linked to hypertriglyceridemia. [21]
The word hypertriglyceridemia uses combining forms of hyper- + triglyceride + -emia , thus corresponding to "high triglyceride levels in the blood" or "too many triglycerides in the blood".[ citation needed ]
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.
Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins, such as cholesterol, in the blood (hyperlipidemia). The American Heart Association recommends the descriptor 'lipid lowering agent' be used for this class of drugs rather than the term 'hypolipidemic'.
In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid. They are used for a range of metabolic disorders, mainly hypercholesterolemia, and are therefore hypolipidemic agents.
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.
Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases, which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for cardiovascular disease, abnormal levels do not mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia.
Chylomicrons, also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids, such as fats and cholesterol, from the intestines to other locations in the body, within the water-based solution of the bloodstream. ULDLs are one of the five major groups lipoproteins are divided into based on their density. A protein specific to chylomicrons is ApoB48.
Combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis it shows as a hyperlipoproteinemia type IIB. It is the most commonly inherited lipid disorder, occurring in around one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 have this disorder.
Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat abnormal blood lipid levels. It is generally less preferred than statins. Use is recommended together with dietary changes and exercise. It is unclear if it changes the risk of heart disease. It is taken by mouth.
Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.
Fenofibrate (sold under the brand name Tricor among others, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein cholesterol. Its use is recommended together with dietary changes.
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.
Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead to problems with the pancreas and liver, which in turn can lead to diabetes. The disorder only occurs if a child acquires the defective gene from both parents. It is managed by restricting fat in diet to less than 20 g/day.
Blood lipids are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its influence on metabolism. Examples of these lipids include cholesterol and triglycerides. The concentration of blood lipids depends on intake and excretion from the intestine, and uptake and secretion from cells. Hyperlipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood, and is a major risk factor for cardiovascular disease.
Ethyl eicosapentaenoic acid, sold under the brand name Vascepa among others, is a medication used to treat dyslipidemia and hypertriglyceridemia. It is used in combination with changes in diet in adults with hypertriglyceridemia ≥ 150 mg/dL. Further, it is often required to be used with a statin.
Familial hypertriglyceridemia is a genetic disorder characterized by the liver overproducing very-low-density lipoproteins (VLDL). As a result, an affected individual will have an excessive number of VLDL and triglycerides on a lipid profile. This genetic disorder usually follows an autosomal dominant inheritance pattern. The disorder presents clinically in patients with mild to moderate elevations in triglyceride levels. Familial hypertriglyceridemia is typically associated with other co-morbid conditions such as hypertension, obesity, and hyperglycemia. Individuals with the disorder are mostly heterozygous in an inactivating mutation of the gene encoding for lipoprotein lipase (LPL). This sole mutation can markedly elevate serum triglyceride levels. However, when combined with other medications or pathologies it can further elevate serum triglyceride levels to pathologic levels. Substantial increases in serum triglyceride levels can lead to certain clinical signs and the development of acute pancreatitis.
A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in blood lipid concentrations. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases.
Omega−3-carboxylic acids (Epanova) is a formerly marketed yet still not a Food and Drug Administration (FDA)-approved prescription medication–since taken off market by the manufacturer–used alongside a low fat and low cholesterol diet that lowers high triglyceride (fat) levels in adults with very high levels. This was the third class of fish oil-based drug, after omega−3-acid ethyl esters and ethyl eicosapentaenoic acid (Vascepa), to be approved for use as a drug. The first approval in the United States by the FDA was granted 05 May 2014. These fish oil drugs are similar to fish oil dietary supplements, but the ingredients are better controlled and have been tested in clinical trials. Specifically, Epanova contained at least 850 mg omega−3-acid ethyl esters per 1 g capsule.
Volanesorsen, sold under the brand name Waylivra, is a triglyceride-reducing drug. It is a second-generation 2'-O-methoxyethyl (2'-MOE) chimeric antisense therapeutic oligonucleotide (ASO) that targets the messenger RNA for apolipoprotein C3 (apo-CIII).