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Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't 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
hyperlipidemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...
s; that is, an elevation of lipids in the blood. This is often due to
diet Diet may refer to: Food * Diet (nutrition), the sum of the food consumed by an organism or group * Dieting, the deliberate selection of food to control body weight or nutrient intake ** Diet food, foods that aid in creating a diet for weight loss ...
and lifestyle. Prolonged elevation of
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.


Types


Diagnosis


Classification

Physicians and basic researchers classify dyslipidemias in two distinct ways. One way is its presentation in the body (including the specific type of lipid that is increased). The other way is due to the underlying cause for the condition ( genetic, or secondary to another condition). This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. However, there are a few well-defined genetic conditions that are usually easy to identify. The three main blood levels collected to assess for dyslipidemia is
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as ...
s(TG),
high density lipoprotein 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 t ...
cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). High triglyceride levels (>1.7 mmol/L fasting) can indicate dyslipidemia. Triglycerides are transported through the blood by using very low density lipoproteins (VLDL) as a carrier. One thing to note when measuring triglyceride levels is that
fasting Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...
for 8–12 hours is required to get an accurate result as non-fasting TG results may be falsely elevated. If TG results are greater than 10 mmol/L, then this needs to be addressed since severe hypertriglceridemia is a risk factor for acute
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...
. Another blood level collected to assess dyslipidemia is HDL-C. HDL cholesterol is made up of very little lipids and a high amount of protein. It is beneficial in the body because it functions by going to the tissues and picking up extra cholestrol and fat. Due to the positive effects of HDL-C, it is named "good cholesterol" since it helps prevent plaque formation. Other functions of HDL-C is promoting cardiovascular health such as antioxidation effects, protection against
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
, maintenance of endothelial function, and maintaining low blood viscosity. Due to the positive functions of HDL cholesterol, a low level indicates dyslipidemia and is a risk factor for complications. Another diagnostic test that is often reviewed is LDL cholesterol. Low density lipoproteins are made up of cholesterol, TG, phospholipids, and
apolipoprotein Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoproteins ...
s. LDL-C molecules bind to the endothelium of blood vessels and cause plaque formation. Once plaques are formed, LDL-C floating in the bloodstream can attach to the plaques and cause further accumulation. In addition to plaque formation, LDL-C molecules can undergo oxidation. Oxidation can cause further accumulation of cholesterol and the release of
inflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include i ...
s, which damages the blood vessels. Due to the damaging effects of LDL-C, high levels increase the risk for cardiovascular disease and indicate dyslipidemia. Dyslipidemias can also be classified based on the underlying cause, whether it is primary, secondary, or a combination of both. Primary dyslipidemias are caused by
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s that can cause abnormal lipid levels without any other obvious risk factors. Those with primary dyslipidemias are at higher risk of getting complications of dyslipidemias, such as
atherosclerotic cardiovascular disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...
, at a younger age. Some common genetic disorders associated with primary dyslipidemias are homozygous or heterozygous hypercholesterolemia, familial hypertriglyceridemia,
combined hyperlipidemia Combined hyperlipidemia (or -aemia) is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electropho ...
, and HDL-C metabolism disorders. In familial hypercholesterolemia, a mutation in the ''LDLR, PCSK9,'' or ''APOB'' is usually the reason for this and these mutations result in high LDL cholesterol. In combined hyperlipidemia, there is an overproduction of apoB-100 in the liver. This causes high amounts of LDL and VLDL molecules to form. A unique sign of primary dyslipidemias is that patients will often present with acute pancreatitis or
xanthoma A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis) is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states. They are cutaneous manifestations of lipidosis in which lip ...
s on the skin, eyelids or around the cornea. In contrast to primary dyslipidemias, secondary dyslipidemas are based on modifiable environmental or lifestyle factors. Some diseases that are associated with a higher risk of dyslipidemia are uncontrolled
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, cholestatic liver disease,
chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
,
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...
, and
polycystic ovarian syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...
. What people eat can also have an influence, with excessive alcohol use, too much carbohydrates, and diets high in saturated fats having a higher risk. Some medications that may contribute to dyslipidemia are thiazide diuretics,
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...
s,
oral contraceptives Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combi ...
,
atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s (clozapine, olanzapine),
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...
s,
tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
, and
cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
. Other non-hereditary factors that increase the risk of dyslipidemias are smoking, pregnancy, and obesity.  The Fredrickson Classification seen below classifies dyslipidemias into categories:


Screening

There is no clear consensus of when screening for dyslipidemia should be initiated. In general, those with a high risk of cardiovascular disease should be screened at a younger age with males between 25 and 30 years old and females between 30 and 35 years of age. Testing the general population under the age of 40 without symptoms is of unclear benefit. UpToDate suggests screening males at age 35 and females at age 45 in those without any risk of cardiovascular disease. All individuals regardless of age, should be screened if they have the risk factors listed below.Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J., Grégoire, J., Grover, S. A., Gupta, M., Hegele, R. A., Lau, D., Leiter, L. A., Leung, A. A., Lonn, E., Mancini, G., Manjoo, P., McPherson, R., Ngui, D., … Wray, W. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. ''The Canadian journal of cardiology'', ''37''(8), 1129–1150. https://doi-org.uml.idm.oclc.org/10.1016/j.cjca.2021.03.016 Cardiovascular risk can be determined using the
Framingham Risk Score The Framingham Risk Score is a sex-specific algorithm used to estimate the 10-year cardiovascular risk of an individual. The Framingham Risk Score was first developed based on data obtained from the Framingham Heart Study, to estimate the 10-year r ...
(FRS) and should be reassessed every 5 years for patients who are 40 to 75 years of age.


Risk Factors

Risk factors include:Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J., Grégoire, J., Grover, S. A., Gupta, M., Hegele, R. A., Lau, D., Leiter, L. A., Leung, A. A., Lonn, E., Mancini, G., Manjoo, P., McPherson, R., Ngui, D., … Wray, W. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. ''The Canadian journal of cardiology'', ''37''(8), 1129–1150. https://doi-org.uml.idm.oclc.org/10.1016/j.cjca.2021.03.016 * Family history of dyslipidemia * Current cigarette smoking * Diabetes mellitus * Hypertension * Obesity (BMI>30 kg/m2) * Atherosclerosis * Family history of premature coronary artery disease * HIV infection * Erectile dysfunction * Chronic kidney disease (eGFR < 60ml/min/1.73 m2) * Abdominal aneurysm * Chronic obstructive pulmonary disease * Clinical manifestations of hyperlipidemias (xanthelasmas, xanthomas, premature arcus cornealis) * Hypertensive disorders of pregnancy * Inflammatory bowel disease


Non-pharmacological Choices

An important non-pharmacological intervention in dyslipidemia is a diet aimed at reducing blood lipid levels and also weight loss if needed. These dietary changes should always be a part of treatment and the involvement of a dietician is recommended in the initial evaluation and also in follow-up as well. A 3-month trial of dietary changes is recommended in primary prevention before considering medication, but in secondary prevention and in individuals at high-risk, cholesterol-lowering medication is used in conjunction with diet modifications.Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J., Grégoire, J., Grover, S. A., Gupta, M., Hegele, R. A., Lau, D., Leiter, L. A., Leung, A. A., Lonn, E., Mancini, G., Manjoo, P., McPherson, R., Ngui, D., … Wray, W. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. ''The Canadian journal of cardiology'', ''37''(8), 1129–1150. https://doi-org.uml.idm.oclc.org/10.1016/j.cjca.2021.03.016 Recommended diets include the
DASH diet The DASH diet (Dietary Approaches to Stop Hypertension) is a dietary pattern promoted by the U.S.-based National Heart, Lung, and Blood Institute (part of the National Institutes of Health (NIH), an agency of the United States Department of Heal ...
,
Mediterranean diet The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incor ...
, Low-glycemic Index diet, Portfolio diet, and vegetarian diet. Patients should reduce their intake of saturated fats, dietary cholesterol, and alcohol, and increase their intake of total fibre (>30g/day), viscous soluble fibre (>10g/day), and omega-3 (EPA and DHA -4g/dused to lower TG only). They should also increase the proportion of mono-and polyunsaturated fats that they intake. Other lifestyle modifications include weight loss (5-10% of body weight loss) and reduction of abdominal obesity, 30–60 minutes per day of moderate-vigorous exercise, smoking cessation, stress management, and getting 6–8 hours of sleep at night.


Pharmacological Choices

Based on the
Framingham Risk Score The Framingham Risk Score is a sex-specific algorithm used to estimate the 10-year cardiovascular risk of an individual. The Framingham Risk Score was first developed based on data obtained from the Framingham Heart Study, to estimate the 10-year r ...
s, there are different thresholds that indicate whether treatment should be initiated. Individuals with a score of >20% are considered to have a high cardiovascular risk, a score of 10-19% indicates an intermediate risk, and patients with a score less than 10% are at low risk. Statin therapy and non-pharmacological interventions are indicated in those with high cardiovascular risk. In those at intermediate risk or low risk, the use of statin therapy depends on individual patient factors such as age, cholesterol levels, and risk factors.Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J., Grégoire, J., Grover, S. A., Gupta, M., Hegele, R. A., Lau, D., Leiter, L. A., Leung, A. A., Lonn, E., Mancini, G., Manjoo, P., McPherson, R., Ngui, D., … Wray, W. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. ''The Canadian journal of cardiology'', ''37''(8), 1129–1150. https://doi-org.uml.idm.oclc.org/10.1016/j.cjca.2021.03.016 Statins are considered the first-line agents but other drugs can be substituted if the lipid targets are not achieved with statin therapy or if they are not tolerated.


HMG-CoA Reductase Inhibitors (

Statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...
s)

Statins competitively inhibit hydroxymethylglutaryl (HMG) CoA reductase which is used in the biosynthesis of cholesterol and they include atorvastatin, lovastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin, and pitavastatin. These agents work to lower LDL-C levels and are also associated with a decrease in CVD mortality, CVD morbidity, and total deaths. They have a small effect on HDL-C levels as well.


Resins

Resins are bile acid sequesterants that work by preventing the intestinal re-uptake of bile acids, thus increasing their fecal loss. Resins include cholestyramine, colestipol, and colesevalem, and they all decrease LDL-C while increasing HDL-C levels slightly. The Lipid Research Council - Cardiovascular Primary Prevention Trial (LRC-CPPT) also showed that when these agents were used alone, they improved cardiovascular outcomes.


Fibrate In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), ...
s

The cholesterol lowering effect of fibrates is due to their ability to activate a nuclear receptor called peroxisome proliferator activated receptor alpha. They include fenofibrate, gemfibrozil, and bezafibrate and work to decrease triglycerides, increase HDL-C, and also decrease LDL-C which is variable depending on which drug is used. The FIELD Study showed that fenofibrate reduced both coronary revascularization as well as nonfatal myocardial infarctions (but not in patients with DM2).


PCSK9 Inhibitors

PCSK9 inhibitors are monoclonal antibodies that target an important protein in the degradation of LDL called proprotein convertase substilisin/kexin type 9 (
PCSK9 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (ortholog ...
). These agents reduce LDL-C, increase HDL-C, decrease triglycerides, and decrease lipoprotein(a). The FOURNIER and ODYSSEY trials showed that these agents also reduced the risk of cardiovascular events.


Cholesterol Absorption Inhibitors

Ezetimibe inhibits the intestinal absorption of cholesterol and can be used alone or with statins. Regarding cardiovascular events, patients with chronic kidney disease saw a reduction in vascular and major atherosclerotic events when on simvastatin and ezetimibe compared to placebo. This same combination was also shown to reduce death, major coronary events, and nonfatal stroke in patients after acute coronary syndromes.


Icosapent Ethyl Ethyl eicosapentaenoic acid (E-EPA, icosapent ethyl), 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 hypertrigly ...

This agent consists of eicosapentaenoic acid (EPA), an omega-3 fatty acid from fish oil and works to lower the hepatic production of triglycerides. In the REDUCE-IT trial, patients on statin therapy and 4g daily of icosapent ethyl saw a reduction in major cardiovascular events.


Microsomal Triglyceride Transfer Protein Inhibitors

Lomitapide Lomitapide , sold under the brand name Juxtapid in the US and Lojuxta in the EU, is a medication used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals. It has been tested in cli ...
works to inhibit the microsomal triglyceride transfer protein (MTP) which results in a reduction of LDL plasma levels.


References

\ {{Lipid metabolism disorders Lipid disorders ja:脂質異常症