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Hypercholesterolemia, also called high cholesterol, is the presence of high levels of
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
in the blood. It is a form of
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 ...
(high levels of
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s in the blood), hyperlipoproteinemia (high levels of
lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...
s in the blood), and
dyslipidemia 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 ar ...
(any abnormalities of lipid and lipoprotein levels in the blood). Elevated levels of non-HDL cholesterol and LDL in the blood may be a consequence of
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 ...
,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, inherited (genetic) diseases (such as
LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor ...
mutations in familial hypercholesterolemia), or the presence of other diseases such as
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
and an underactive thyroid. Cholesterol is one of three major classes of
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s produced and used by all animal cells to form membranes. Plant cells manufacture phytosterols (similar to cholesterol), but in rather small quantities. Cholesterol is the precursor of the
steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...
s and
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...
s. Since cholesterol is insoluble in water, it is transported in the blood plasma within protein particles (
lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...
). Lipoproteins are classified by their density:
very low density lipoprotein Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipo ...
(VLDL), intermediate density lipoprotein (IDL),
low density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
(LDL) and
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 ty ...
(HDL). All the lipoproteins carry cholesterol, but elevated levels of the lipoproteins other than HDL (termed non-HDL cholesterol), particularly LDL-cholesterol, are associated with an increased risk of
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
and
coronary heart 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 pla ...
. In contrast, higher levels of HDL cholesterol are protective. Avoiding
trans fats Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial p ...
and replacing
saturated fats A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched c ...
in adult diets with
polyunsaturated fats 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. The term often refers specifically to triglycerides (triple est ...
are recommended dietary measures to reduce total blood cholesterol and LDL in adults. In people with very high cholesterol (e.g., familial hypercholesterolemia), diet is often not sufficient to achieve the desired lowering of LDL, and lipid-lowering
medications A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
are usually required. If necessary, other treatments such as LDL
apheresis Apheresis ( ἀφαίρεσις (''aphairesis'', "a taking away")) is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation ...
or even surgery (for particularly severe subtypes of familial hypercholesterolemia) are performed. About 34 million adults in the United States have high blood cholesterol.


Signs and symptoms

Although hypercholesterolemia itself is
asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
, longstanding elevation of serum cholesterol can lead to
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
(hardening of arteries). Over a period of decades, elevated serum cholesterol contributes to formation of
atheromatous plaques An atheroma, or atheromatous plaque, is an abnormal and reversible accumulation of material in the inner layer of an arterial wall. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount o ...
in the arteries. This can lead to progressive narrowing of the involved arteries. Alternatively smaller plaques may rupture and cause a clot to form and obstruct blood flow. A sudden blockage of a coronary artery may result in a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
. A blockage of an artery supplying the brain can cause a
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
. If the development of the stenosis or occlusion is gradual, blood supply to the tissues and organs slowly diminishes until organ function becomes impaired. At this point tissue
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
(restriction in blood supply) may manifest as specific
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s. For example, temporary ischemia of the brain (commonly referred to as a
transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same Symptoms of stroke, symptoms associated with strokes, such as weakness or numbn ...
) may manifest as temporary loss of vision,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...
and impairment of
balance Balance or balancing may refer to: Common meanings * Balance (ability) in biomechanics * Balance (accounting) * Balance or weighing scale * Balance as in equality or equilibrium Arts and entertainment Film * ''Balance'' (1983 film), a Bulgaria ...
, difficulty speaking,
weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
or numbness or tingling, usually on one side of the body. Insufficient blood supply to the heart may cause
chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...
, and ischemia of the eye may manifest as transient visual loss in one eye. Insufficient blood supply to the legs may manifest as calf pain when walking, while in the intestines it may present as abdominal pain after eating a meal. Some types of hypercholesterolemia lead to specific physical findings. For example, familial hypercholesterolemia (Type IIa hyperlipoproteinemia) may be associated with
xanthelasma palpebrarum Xanthelasma is a sharply demarcated yellowish deposit of cholesterol underneath the skin. It usually occurs on or around the eyelids (''xanthelasma palpebrarum'', abbreviated XP). While they are neither harmful to the skin nor Pain, painful, these ...
(yellowish patches underneath the skin around the eyelids),
arcus senilis Arcus senilis (AS), also known as gerontoxon, arcus lipoides, arcus corneae, corneal arcus, arcus adiposus, or arcus cornealis, are rings in the peripheral cornea. It‘s usually caused by cholesterol deposits, so it may be a sign of high choleste ...
(white or gray discoloration of the peripheral
cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
), and
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 ...
ta (deposition of yellowish cholesterol-rich material) of the
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...
s, especially of the fingers. Type III hyperlipidemia may be associated with xanthomata of the palms, knees and elbows.


Causes

Hypercholesterolemia is typically due to a combination of environmental and genetic factors. Environmental factors include weight,
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
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
.
Loneliness Loneliness is an unpleasant emotional response to perceived isolation. Loneliness is also described as social paina psychological mechanism which motivates individuals to seek social connections. It is often associated with a perceived lack ...
is also a risk factor.


Diet

Diet has an effect on blood cholesterol, but the size of this effect varies between individuals. A diet high in
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
or saturated fats increases total cholesterol and LDL.
Trans fats Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial p ...
have been shown to reduce levels of HDL while increasing levels of LDL. A 2016 review found tentative evidence that dietary cholesterol is associated with higher blood cholesterol. As of 2018 there appears to be a modest positive, dose-related relationship between cholesterol intake and LDL cholesterol.


Medical conditions and treatments

A number of other conditions can also increase cholesterol levels including
diabetes mellitus type 2 Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, alcohol use,
monoclonal gammopathy Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, espec ...
, dialysis therapy, nephrotic syndrome,
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 po ...
,
Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a ...
and
anorexia nervosa Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
. Several medications and classes of medications may interfere with lipid metabolism:
thiazide diuretics Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...
,
ciclosporin 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 ...
,
glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
,
beta blockers 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 ...
,
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...
,
antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
s), certain
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s and medications for HIV as well as
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...
s.


Genetics

Genetic contributions are usually due to the additive effects of multiple genes ("polygenic"), though occasionally may be due to a single gene defect such as in the case of
familial hypercholesterolaemia Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL cholesterol), in the blood and early cardiovascular disease. The most common mutatio ...
. In familial hypercholesterolemia, mutations may be present in the
APOB Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Function Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles (LDL—commonly known as "bad cholesterol" when in refer ...
gene (
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
), the
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
''
LDLRAP1 Low-density lipoprotein receptor adapter protein 1 is a protein that in humans is encoded by the ''LDLRAP1'' gene. The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTB) domain. The PTB domain has b ...
'' gene, autosomal dominant familial hypercholesterolemia (''HCHOLA3'') variant of the ''
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 ...
'' gene, or the LDL receptor gene. Familial hypercholesterolemia affects about one in 250 individuals.


Diagnosis

Cholesterol is measured in milligrams per deciliter (mg/dL) of blood in the United States and some other countries. In the United Kingdom, most European countries and Canada, millimoles per liter of blood (mmol/L) is the measure.High Cholesterol – Tests and Diagnosis
Mayo Clinic staff. Retrieved 2013-03-09.
For healthy adults, the UK National Health Service recommends upper limits of total cholesterol of 5 mmol/L, and low-density lipoprotein cholesterol (LDL) of 3 mmol/L. For people at high risk of cardiovascular disease, the recommended limit for total cholesterol is 4 mmol/L, and 2 mmol/L for LDL.Diagnosing High Cholesterol
NHS Choices. Retrieved 2013-03-09.
In the United States, the National Heart, Lung, and Blood Institute within the National Institutes of Health classifies total cholesterol of less than 200 mg/dL as "desirable", 200 to 239 mg/dL as "borderline high", and 240 mg/dL or more as "high".ATP III Guidelines At-A-Glance Quick Desk Reference
National Cholesterol Education Program. Retrieved 2013-03-09.
There is no absolute cutoff between normal and abnormal cholesterol levels, and values must be considered in relation to other health conditions and risk factors. Higher levels of total cholesterol increase the risk of cardiovascular disease, particularly coronary heart disease. Levels of LDL or non-HDL cholesterol both predict future coronary heart disease; which is the better predictor is disputed. High levels of small dense LDL may be particularly adverse, although measurement of small dense LDL is not advocated for risk prediction. In the past, LDL and VLDL levels were rarely measured directly due to cost. Levels of fasting
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 w ...
s were taken as an indicator of VLDL levels (generally about 45% of fasting triglycerides is composed of VLDL), while LDL was usually estimated by the Friedewald formula: LDL \approx total cholesterol – HDL – (0.2 x fasting triglycerides). However, this equation is not valid on nonfasting blood samples or if fasting triglycerides are elevated (>4.5 mmol/L or >∼400 mg/dL). Recent guidelines have, therefore, advocated the use of direct methods for measurement of LDL wherever possible. It may be useful to measure all lipoprotein subfractions (
VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipo ...
, IDL,
LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
, and HDL) when assessing hypercholesterolemia and measurement of apolipoproteins and lipoprotein (a) can also be of value. Genetic screening is now advised if a form of familial hypercholesterolemia is suspected.


Classification

Classically, hypercholesterolemia was categorized by lipoprotein
electrophoresis Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fie ...
and the
Fredrickson classification 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 ...
. Newer methods, such as "lipoprotein subclass analysis", have offered significant improvements in understanding the connection with atherosclerosis progression and clinical consequences. If the hypercholesterolemia is hereditary ( familial hypercholesterolemia), more often a
family history Genealogy () is the study of families, family history, and the tracing of their Lineage (anthropology), lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family a ...
of premature, earlier onset atherosclerosis is found.


Screening method

The
U.S. Preventive Services Task Force The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
in 2008 strongly recommends routine screening for men 35 years and older and women 45 years and older for lipid disorders and the treatment of abnormal lipids in people who are at increased risk of coronary heart disease. They also recommend routinely screening men aged 20 to 35 years and women aged 20 to 45 years if they have other risk factors for
coronary heart 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 pla ...
. In 2016 they concluded that testing the general population under the age of 40 without symptoms is of unclear benefit. In Canada, screening is recommended for men 40 and older and women 50 and older. In those with normal cholesterol levels, screening is recommended once every five years. Once people are on a statin further testing provides little benefit except possibly to determine compliance with treatment.


Treatment

Treatment recommendations have been based on four risk levels for heart disease. For each risk level, LDL cholesterol levels representing goals and thresholds for treatment and other action are made. The higher the risk category, the lower the cholesterol thresholds. For those at high risk, a combination of lifestyle modification and statins has been shown to decrease mortality.


Lifestyle

Lifestyle changes recommended for those with high cholesterol include: smoking cessation, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight. Overweight or obese individuals can lower blood cholesterol by losing weight – on average a kilogram of weight loss can reduce LDL cholesterol by 0.8 mg/dl.


Diet

Eating a diet with a high proportion of vegetables, fruit, dietary fibre, and low in fats results in a modest decrease in total cholesterol. Eating dietary cholesterol causes a small rise in serum cholesterol, the magnitude of which can be predicted using the Keys and Hegsted equations. Dietary limits for cholesterol were proposed in United States, but not in Canada, United Kingdom, and Australia. However, in 2015 the
Dietary Guidelines Advisory Committee The United States Department of Agriculture (USDA) is the United States federal executive departments, federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, ...
in the United States removed its recommendation of limiting cholesterol intake. A 2020 Cochrane review found replacing saturated fat with polyunsaturated fat resulted in a small decrease in
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
by decreasing blood cholesterol. Other reviews have not found an effect from saturated fats on cardiovascular disease.
Trans fats Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial p ...
are recognized as a potential risk factor for cholesterol-related cardiovascular disease, and avoiding them in an adult diet is recommended. The
National Lipid Association The National Lipid Association (NLA) is an American non-profit multidisciplinary medical society that aims to enhance the practice of lipid management in clinical medicine. The NLA focuses on the prevention of cardiovascular disease and other lipid ...
recommends that people with familial hypercholesterolemia restrict intakes of total fat to 25–35% of energy intake, saturated fat to less than 7% of energy intake, and cholesterol to less than 200 mg per day. Changes in total fat intake in low calorie diets do not appear to affect blood cholesterol. Increasing soluble fiber consumption has been shown to reduce levels of LDL cholesterol, with each additional gram of soluble fiber reducing LDL by an average of 2.2 mg/dL (0.057 mmol/L). Increasing consumption of whole grains also reduces LDL cholesterol, with whole grain oats being particularly effective. Inclusion of 2 g per day of
phytosterols Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phytos ...
and phytostanols and 10 to 20 g per day of soluble fiber decreases dietary cholesterol absorption. A diet high in
fructose Fructose, or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galacto ...
can raise LDL cholesterol levels in the blood.


Medication

Statins are the typically used medications, in addition to healthy lifestyle interventions. Statins can reduce total cholesterol by about 50% in the majority of people, and are effective in reducing the risk of cardiovascular disease in both people with and without pre-existing cardiovascular disease. In people without cardiovascular disease, statins have been shown to reduce all-cause mortality, fatal and non-fatal coronary heart disease, and strokes. Greater benefit is observed with the use of high-intensity statin therapy. Statins may improve
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
when used in people without existing cardiovascular disease (i.e. for primary prevention). Statins decrease cholesterol in children with hypercholesterolemia, but no studies as of 2010 show improved outcomes and diet is the mainstay of therapy in childhood. Other agents that may be used include
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, nicotinic acid, and
cholestyramine Colestyramine ( INN) or cholestyramine ( USAN) (trade names Questran, Questran Light, Cholybar, Olestyr) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong ion exchange resin, wh ...
. These, however, are only recommended if statins are not tolerated or in pregnant women. Injectable antibodies against the protein
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 ...
(
evolocumab Evolocumab (trade name Repatha) is a monoclonal antibody medication designed for the treatment of hyperlipidemia. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a pro ...
, bococizumab,
alirocumab Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a ...
) can reduce LDL cholesterol and have been shown to reduce mortality.


Guidelines

In the US, guidelines exist from the
National Cholesterol Education Program {{Primary sources, article, date=May 2011The 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 cardiovascula ...
(2004) and a joint body of professional societies led by the
American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...
. In the UK, the
National Institute for Health and Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...
has made recommendations for the treatment of elevated cholesterol levels, published in 2008, and a new guideline appeared in 2014 that covers the prevention of cardiovascular disease in general. The Task Force for the management of dyslipidaemias of the European Society of Cardiology and the European Atherosclerosis Society published guidelines for the management of dyslipidaemias in 2011.


Specific populations

Among people whose
life expectancy Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
is relatively short, hypercholesterolemia is not a risk factor for death by any cause including
coronary heart 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 pla ...
. Among people older than 70, hypercholesterolemia is not a risk factor for being hospitalized with
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
or angina. There are also increased risks in people older than 85 in the use of
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 ...
drugs. Because of this, medications which lower lipid levels should not be routinely used among people with limited life expectancy. The
American College of Physicians The American College of Physicians (ACP) is a national organization of internists, who specialize in the diagnosis, treatment, and care of adults.Sokanu "What is an Internist?" Retrieved October 20, 2014 With 161,000 members, ACP is the largest ...
recommends for hypercholesterolemia in people with
diabetes 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 ap ...
: # Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all adults with known coronary artery disease and type 2 diabetes. # Statins should be used for primary prevention against macrovascular complications in adults with type 2 diabetes and other cardiovascular risk factors. # Once lipid-lowering therapy is initiated, people with type 2 diabetes mellitus should be taking at least moderate doses of a statin. # For those people with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.


Alternative medicine

According to a survey in 2002,
alternative medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...
was used in an attempt to treat cholesterol by 1.1% of U.S. adults. Consistent with previous surveys, this one found the majority of individuals (55%) used it in conjunction with
conventional medicine Medicine is the science and Praxis (process), practice of caring for a patient, managing the diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, and Health promotion ...
. A systematic review of the effectiveness of
herbal medicine Herbal medicine (also herbalism) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. With worldwide research into pharmacology, some herbal medicines have been translated into modern remed ...
s utilized in
traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action ...
had inconclusive results due to the poor methodological quality of the included studies. A review of trials of
phytosterols Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phytos ...
and/or phytostanols, average dose 2.15 g/day, reported an average of 9% lowering of LDL-cholesterol. In 2000, the Food and Drug Administration approved the labeling of foods containing specified amounts of phytosterol esters or phytostanol esters as cholesterol-lowering; in 2003, an FDA Interim Health Claim Rule extended that label claim to foods or dietary supplements delivering more than 0.8 g/day of phytosterols or phytostanols. Some researchers, however, are concerned about diet supplementation with plant sterol esters and draw attention to lack of long-term safety data.


Epidemiology

Rates of high total cholesterol in the United States in 2010 are just over 13%, down from 17% in 2000. Average total cholesterol in the United Kingdom is 5.9 mmol/L, while in rural China and Japan, average total cholesterol is 4 mmol/L. Rates of coronary artery disease are high in Great Britain, but low in rural China and Japan.


Research directions

Gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
is being studied as a potential treatment.


References


External links

{{Medical resources , DiseasesDB = 6226 , ICD10 = {{ICD10, E, 78, 0, e, 70 , ICD9 = {{ICD9, 272.0 , OMIM = , MedlinePlus = 000403 , ICDO = , eMedicineSubj = med , eMedicineTopic = 1073 , MeshID = D006937 Cholesterol and steroid metabolism disorders Lipid metabolism disorders Medical conditions related to obesity