Hypertriglyceridemia
Encyclopedia
In medicine
, hypertriglyceridemia denotes high (hyper-) blood levels (-emia) of triglyceride
s, the most abundant fat
ty molecule in most organisms. It has been associated with atherosclerosis
, even in the absence of hypercholesterolemia
(high cholesterol
levels). It can also lead to pancreatitis
in excessive concentrations (i.e. when the triglyceride concentration is greater, and often very much greater, than 1000 mg/dl or 12 mmol/l). Very high triglyceride levels may also interfere with blood test
s; hyponatremia
may be reported spuriously (pseudohyponatremia).
A related term is "hyperglyceridemia" which refers to a high level of all glyceride
s, including monoglycerides, diglycerides and triglycerides.
), eruptive xanthoma
s (small lumps in the skin, sometimes itchy).
In other words, any study purporting to demonstrate an association of hypertriglyceridemia and atheroslerosis must not only have controlled for the classic atherosclerosis risk factors but also for the more recently recognized risk factors such as insulin resistance, levels of small, dense LDL, and apoB levels. The relationship among hypertriglyceridemia, atherosclerosis, and apoB is particularly instructive. Specifically, those forms of hypertriglyceridemia associated with high levels of apoB, but not those associated with low levels of apoB, are associated with atherosclerosis.
, as well as with niacin
, fibrate
s and statin
s (three classes of drugs). Increased fish oil
intake may substantially lower an individual's triglycerides.
Clinical practice guidelines by the National Cholesterol Education Program
(NCEP) suggest that pharmacotherapy should be considered for a triglycerides level over 200 mg/dL. The guidelines state "the sum of LDL + VLDL cholesterol (termed non-HDL cholesterol [total cholesterol - HDL cholesterol]) as a secondary target of therapy in persons with high triglycerides (200 mg/dL). The goal for non-HDL cholesterol in persons with high serum triglycerides can be set at 30 mg/dL higher than that for LDL cholesterol (Table 9) on the premise that a VLDL cholesterol level 30 mg/dL is normal."
Non–HDL cholesterol contains the highly atherogenic, small, dense lipoproteins that are associated with a high incidence of cardiovascular disease (CVD). Studies subsequent to the NCEP report have shown that the non–HDL cholesterol level predicts CVD in people who have diabetes. It may be superior to LDL cholesterol in this regard, and should be used as the primary lipid target in persons with diabetes.
supplementation in the form of fish oil has been found to be effective in decreasing levels of triglycerides and all cardiovascular events by 19% to 45%.
Gemfibrozil
twice daily in asymptomatic men ages 40–55 without heart disease was also found to be effective at reducing cardiac endpoints at 5 years (4.14% to 2.73%). This means that 71 people must take the treatment for five years to prevent one cardiac event (number needed to treat
of 71).
of men with known heart disease and HDL cholesterol of 40 mg/dl or less, 600 mg of gemfibrozil twice daily reduced cardiac endpoints (non-fatal myocardial infarction or death from coronary causes) at 5 years from 21.7% to 17.3%. This means that 23 patients must be treated for five years to prevent one cardiac event (number needed to treat
is 23).
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, hypertriglyceridemia denotes high (hyper-) blood levels (-emia) of triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s, the most abundant fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
ty molecule in most organisms. It has been associated with atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, even in the absence of hypercholesterolemia
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
(high cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels). It can also lead to pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
in excessive concentrations (i.e. when the triglyceride concentration is greater, and often very much greater, than 1000 mg/dl or 12 mmol/l). Very high triglyceride levels may also interfere with blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s; hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
may be reported spuriously (pseudohyponatremia).
A related term is "hyperglyceridemia" which refers to a high level of all glyceride
Glyceride
Glycerides, more correctly known as acylglycerols, are esters formed from glycerol and fatty acids.Glycerol has three hydroxyl functional groups, which can be esterified with one, two, or three fatty acids to form monoglycerides, diglycerides, and triglycerides.Vegetable oils and animal fats...
s, including monoglycerides, diglycerides and triglycerides.
Signs and symptoms
Modestly elevated triglyceride levels do not lead to any physical symptoms. Higher levels are associated with lipemia retinalis (white appearance of the retinaRetina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
), eruptive xanthoma
Xanthoma
A xanthoma , from Greek xanthos, ξανθος, "yellow", is a deposition of yellowish cholesterol-rich material in tendons or other body parts in various disease states...
s (small lumps in the skin, sometimes itchy).
Causes
- High carbohydrateCarbohydrateA carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
diet - IdiopathicIdiopathicIdiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
(constitutional) - ObesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
- Diabetes mellitusDiabetes mellitusDiabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
and insulin resistanceInsulin resistanceInsulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
- it is one of the defined components of metabolic syndromeMetabolic syndromeMetabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
(along with central obesityCentral obesityAbdominal obesity, colloquially known as belly fat or clinically as central obesity, is the accumulation of abdominal fat resulting in an increase in waist size...
, hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, and hyperglycemiaHyperglycemiaHyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
) - Excess alcoholAlcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
intake - renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, Nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine.... - Genetic predisposition; some forms of familial hyperlipidemiaHyperlipidemiaHyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
such as familial combined hyperlipidemiaCombined hyperlipidemiaIn medicine, combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL...
i.e. Type II hyperlipidemia - Lipoprotein lipase deficiencyLipoprotein lipase deficiencyLipoprotein lipase deficiency is caused by a mutation in the gene which codes lipoprotein lipase....
- Deficiency of this water soluble enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, that hydrolyzes triglycerideTriglycerideA triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s in lipoproteinLipoproteinA lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s, leads to elevated levels of triglycerides in the blood. - Lysosomal acid lipase deficiencyLysosomal Acid Lipase DeficiencyLysosomal Acid Lipase Deficiency happens when the body does not produce enough active LAL enzyme. Under normal conditions, the body produces an enzyme called lysosomal acid lipase . This enzyme plays an important role in breaking down fatty material in the body...
or Cholesteryl ester storage diseaseCholesteryl ester storage diseaseCholesteryl Ester Storage Disease is the late onset phenotype for Lysosomal Acid Lipase Deficiency, a Lysosomal storage disease, which also has an early onset phenotype known as Wolman disease that primarily affects infants. CESD can present in childhood but often goes unrecognized until... - Certain medications e.g. isotretinoinIsotretinoinIsotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
, estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, hydrochlorothiazideHydrochlorothiazideHydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...
diuretics, beta blockers, protease inhibitors - HypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(underactive thyroid) - Systemic Lupus ErythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
- Glycogen storage disease type 1.
Relationship of Hypertriglyceridemia to Atherosclerosis
Since triglycerides are not a component of the atherosclerotic plaque, it is not intuitively obvious whether hypertriglyceridemia promotes atherosclerosis. Numerous studies (summarized in references ) have examined the relationship between hypertriglyceridemia and atherosclerosis with a definitive answer still not apparent. In large part, the conflicting results reflect whether various other relevant risk factors for atherosclerosis were examined and taken into account. Specifically, the following are all risk factors for atherosclerosis and all are also associated with (not necessarily in a causal way) hypertriglyceridemia:- obesity
- diabetes and insulin resistanceInsulin resistanceInsulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
- metabolic syndromeMetabolic syndromeMetabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
- presence of other dyslipidemias associated themselves both with high triglycerides and atherosclerosis (e.g. mixed hyperlipidemia, low HDL (hypoalphalipoproteinemiaHypoalphalipoproteinemiaHypoalphalipoproteinemia is a high-density lipoprotein deficiency, inherited in an autosomal dominant manner.It can be associated with LDL receptor.Associated regions and genes include:Niacin is sometimes prescribed to raise HDL levels....
), Familial dysbetalipoproteinemiaFamilial dysbetalipoproteinemiaFamilial dysbetalipoproteinemia is a condition characterized by increased LDL, triglyceride, and cholesterol levels, and decreased HDL levels...
(type III hyperlipoproteinemia), etc.) - high levels of small, dense LDL
- high levels of apolipoprotein BApolipoprotein BApolipoprotein B is the primary apolipoprotein of low-density lipoproteins , which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation...
(apoB)
In other words, any study purporting to demonstrate an association of hypertriglyceridemia and atheroslerosis must not only have controlled for the classic atherosclerosis risk factors but also for the more recently recognized risk factors such as insulin resistance, levels of small, dense LDL, and apoB levels. The relationship among hypertriglyceridemia, atherosclerosis, and apoB is particularly instructive. Specifically, those forms of hypertriglyceridemia associated with high levels of apoB, but not those associated with low levels of apoB, are associated with atherosclerosis.
Treatment
Treatment of hypertriglyceridemia is by restriction of carbohydrates and fat in the dietDiet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
, as well as with niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
, fibrate
Fibrate
In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia , and are therefore hypolipidemic agents.- Members :...
s and statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s (three classes of drugs). Increased fish oil
Fish oil
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid , and docosahexaenoic acid , precursors of certain eicosanoids that are known to reduce inflammation throughout the body, and are thought to have many health benefits.Fish do not...
intake may substantially lower an individual's triglycerides.
Clinical practice guidelines by the National Cholesterol Education Program
National Cholesterol Education Program
The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. Its goal is to reduce increased cardiovascular disease rates due to hypercholesterolemia in the United States of America...
(NCEP) suggest that pharmacotherapy should be considered for a triglycerides level over 200 mg/dL. The guidelines state "the sum of LDL + VLDL cholesterol (termed non-HDL cholesterol [total cholesterol - HDL cholesterol]) as a secondary target of therapy in persons with high triglycerides (200 mg/dL). The goal for non-HDL cholesterol in persons with high serum triglycerides can be set at 30 mg/dL higher than that for LDL cholesterol (Table 9) on the premise that a VLDL cholesterol level 30 mg/dL is normal."
Non–HDL cholesterol contains the highly atherogenic, small, dense lipoproteins that are associated with a high incidence of cardiovascular disease (CVD). Studies subsequent to the NCEP report have shown that the non–HDL cholesterol level predicts CVD in people who have diabetes. It may be superior to LDL cholesterol in this regard, and should be used as the primary lipid target in persons with diabetes.
Primary prevention
Omega-3 fatty acidOmega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
supplementation in the form of fish oil has been found to be effective in decreasing levels of triglycerides and all cardiovascular events by 19% to 45%.
Gemfibrozil
Gemfibrozil
Gemfibrozil is the generic name for an oral drug used to lower lipid levels. It belongs to a group of drugs known as fibrates. It is most commonly sold as the brand name, Lopid...
twice daily in asymptomatic men ages 40–55 without heart disease was also found to be effective at reducing cardiac endpoints at 5 years (4.14% to 2.73%). This means that 71 people must take the treatment for five years to prevent one cardiac event (number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
of 71).
Secondary prevention
A randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
of men with known heart disease and HDL cholesterol of 40 mg/dl or less, 600 mg of gemfibrozil twice daily reduced cardiac endpoints (non-fatal myocardial infarction or death from coronary causes) at 5 years from 21.7% to 17.3%. This means that 23 patients must be treated for five years to prevent one cardiac event (number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
is 23).