High-density lipoprotein (HDL) is one of the five major groups 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. Lipoproteins are complex particles composed of multiple proteins which transport all
fat
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers specif ...
molecules (
lipid
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
s) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle (organized by one, two or three
ApoA). HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.
HDL particles are commonly referred to as "good cholesterol", because they transport fat molecules out of artery walls, reduce
macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
accumulation, and thus help prevent or even regress
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
.
[
]
Overview
Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. The lipids carried include cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils.
Cholesterol is biosynthesis, biosynthesized by all anima ...
, phospholipids
Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...
, and triglycerides
A triglyceride (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids.
Triglycerides are the main constituents of body fat in humans and oth ...
, amounts of each are variable.
HDL particles remove fats and cholesterol from cells, including within artery
An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
wall atheroma
An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the tunica intima, inner layer of an arterial wall.
The material consists of mostly macrophage, macrophage cells, or debris, containing lipids, calcium and a variabl ...
, and transport it back to the liver for excretion or re-use. Increasing concentrations of HDL particles in the blood are associated with decreasing accumulation of atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
within the walls of arteries, reducing the risk of sudden plaque ruptures, cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
, stroke
Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
and other vascular disease
Vascular disease is a class of diseases of the vessels of the circulatory system in the human body, body, including blood vessels – the arteries and veins, and the lymphatic vessels. Vascular disease is a subgroup of cardiovascular disease. Diso ...
s.[ People with higher levels of HDL-C tend to have fewer problems with ]cardiovascular diseases
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheuma ...
, while those with low HDL-C levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people.
However, a higher blood level of HDL is not necessarily protective against cardiovascular disease and may even be harmful in extremely high quantities, with an increased cardiovascular risk, especially in hypertensive patients.
Testing
Because of the high cost of directly measuring HDL particles, blood tests
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cho ...
commonly measure a surrogate value, HDL-cholesterol (HDL-C), i.e. the cholesterol associated with HDL particles.
HDL-C is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles, known as LDL-C, with HDL-C being nicknamed "good cholesterol" and LDL-C "bad cholesterol".
In healthy individuals, about 30% of blood cholesterol, along with other fats, is carried by HDL. This is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles, 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 called LDL-C. HDL particles remove fats and cholesterol from cells, including within artery
An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
wall atheroma
An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the tunica intima, inner layer of an arterial wall.
The material consists of mostly macrophage, macrophage cells, or debris, containing lipids, calcium and a variabl ...
, and transport it back to the liver for excretion or re-utilization; thus the cholesterol carried within HDL particles (HDL-C) is sometimes called "good cholesterol". Those with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheuma ...
, while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people.
The remainder of the serum cholesterol after subtracting the HDL is the non-HDL cholesterol. The concentration of these other components, which may cause atheroma
An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the tunica intima, inner layer of an arterial wall.
The material consists of mostly macrophage, macrophage cells, or debris, containing lipids, calcium and a variabl ...
, is known as the non-HDL-C. This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated.
Structure and function
With a size ranging from 5 to 17 nm, HDL is the smallest of the 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 ...
particles.[ It is the densest because it contains the highest proportion of ]protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
to lipids
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...
.[ Its most abundant ]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 lipoprotei ...
s are apo A-I and apo A-II. A rare genetic variant, ApoA-1 Milano
Apolipoprotein A-I Milano (also ETC-216, now MDCO-216) is a naturally occurring genetic mutation, mutated variant of the apolipoprotein A1 protein found in human high density lipoprotein, HDL, the lipoprotein particle that carries cholesterol from ...
, has been documented to be far more effective in both protecting against and regressing arterial disease, atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
.
The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles,[ whose NMR structure was published; the complexes are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1).] A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually causing the newly synthesized HDL to assume a spherical shape. HDL particles increase in size as they circulate through the blood and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, such as by interaction with the ABCG1
ATP-binding cassette sub-family G member 1 is a protein that in humans is encoded by the ''ABCG1'' gene. It is a homolog of the well-known ''Drosophila'' gene ''white''.
Function
The protein encoded by this gene is a member of the superfamily ...
transporter and the phospholipid transport protein (PLTP).[
HDL transports cholesterol mostly to the ]liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
or steroidogenic organs such as adrenal
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
s, ovary
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...
, and testes
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone.
The ...
by both direct and indirect pathways. HDL is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester transfer protein (CETP).[ This protein exchanges triglycerides of ]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, LDL, low-density ...
against cholesteryl esters of HDL. As the result, VLDLs are processed to 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 ...
, which are removed from the circulation by the 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 ...
pathway. The triglycerides are not stable in HDL, but are degraded by hepatic lipase
Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC (for "lipase, hepatic"), is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referre ...
so that, finally, small HDL particles are left, which restart the uptake of cholesterol from cells.[
The cholesterol delivered to the liver is excreted into the ]bile
Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
and, hence, intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
either directly or indirectly after conversion into 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 in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
s. Delivery of HDL cholesterol to adrenals, ovaries, and testes is important for the synthesis of 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). Wit ...
s.[
Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden ]macrophages
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
of atherosclerotic
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...
arteries
An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
, termed foam cell
Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger myocardial infarction and stroke.
Foam cells are fat-laden cells with a M2 macro ...
s, to the liver for secretion into the bile. This pathway has been termed ''reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine.
Enhancing reverse cholesterol transport is considered a po ...
'' and is considered as the classical protective function of HDL toward atherosclerosis.
HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and its protein and lipid constituents help to inhibit oxidation
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
, inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, activation of the endothelium, coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
, and platelet aggregation
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...
. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known which are the most important. In addition, a small subfraction of HDL lends protection against the protozoan parasite ''Trypanosoma brucei
''Trypanosoma brucei'' is a species of parasitic Kinetoplastida, kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is excl ...
brucei''. This HDL subfraction, termed trypanosome lytic factor (TLF), contains specialized proteins that, while very active, are unique to the TLF molecule.
In the stress response
The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first describ ...
, serum amyloid A, which is one of the acute-phase proteins
Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute-p ...
and an apolipoprotein, is under the stimulation of cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s (interleukin 1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
, interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene.
In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...
), and cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone.
Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
produced in the adrenal cortex
The adrenal cortex is the outer region and also the largest part of the adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. I ...
and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...
.
It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles. This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either electrophoresis
Electrophoresis is the motion of charged dispersed particles or dissolved charged molecules relative to a fluid under the influence of a spatially uniform electric field. As a rule, these are zwitterions with a positive or negative net ch ...
(the original method developed in the 1970s) or newer NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...
methods (See also nuclear magnetic resonance
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...
and spectroscopy
Spectroscopy is the field of study that measures and interprets electromagnetic spectra. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum.
Spectro ...
), developed in the 1990s.
Subfractions
Five subfractions of HDL have been identified. From largest (and most effective in cholesterol removal) to smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c.
Epidemiology
Men tend to have noticeably lower HDL concentrations, with smaller size and lower cholesterol content, than women. Men also have a greater incidence of atherosclerotic
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...
heart disease. Studies confirm the fact that HDL has a buffering role in balancing the effects of the hypercoagulable state in type 2 diabetics and decreases the high risk of cardiovascular complications in these patients. Also, the results obtained in this study revealed that there was a significant negative correlation between HDL and activated partial thromboplastin time (APTT).
Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
s such as ischemic stroke and myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for atherosclerotic
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...
diseases.
Data from the landmark Framingham Heart Study
The Framingham Heart Study is a long-term, ongoing cardiovascular cohort study of residents of the city of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of partic ...
showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high.
Even people with very low LDL levels achieved by statin
Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease.
Low-density lipoprotein (LDL) carriers of cholesterol play ...
treatment are exposed to increased risk if their HDL levels are not high enough.
Very high HDL-C levels (≥80 mg/dL in men, ≥100 mg/dL in women) appears to be detrimental to cardiovascular outcomes. Several genetic conditions cause abnormally low or high HDL-C levels, often without the expected change in cardiovascular disease rates. In fact, when many known correlates of CVD risks are controlled for, HDL-C does not have any correlation with cardiovascular event risks. In this way, HDL-C only seems to serve as an imperfect, but easy-to-measure, proxy for a healthy lifestyle. What does correlate well with CVD risks even when these factors are controlled for is a direct measure of the capability for reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine.
Enhancing reverse cholesterol transport is considered a po ...
in a person's blood serum, the ''cholesterol efflux capacity'' (CEC).
Estimating HDL via associated cholesterol
Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg2+, then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques. Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then a colorimetric
Colorimetry is "the science and technology used to quantify and describe physically the human color perception".
It is similar to spectrophotometry, but is distinguished by its interest in reducing spectra to the physical correlates of color p ...
enzyme reaction measures cholesterol in the non-blocked HDL particles. HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can origina ...
can also be used. Subfractions (HDL-2C, HDL-3C) can be measured, but clinical significance of these subfractions has not been determined. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.
Recommended ranges
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 Heart, cardiac care in an effort to reduce disability ...
, NIH
The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
and NCEP provide a set of guidelines for fasting HDL levels and risk for heart disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
.
High LDL with low HDL level is an additional risk factor for cardiovascular disease.
Measuring HDL concentration and sizes
As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations and size (which indicates function) at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods.
Electrophoresis measurements
Since the HDL particles have a net negative charge and vary by density & size, ultracentrifugation combined with electrophoresis
Electrophoresis is the motion of charged dispersed particles or dissolved charged molecules relative to a fluid under the influence of a spatially uniform electric field. As a rule, these are zwitterions with a positive or negative net ch ...
have been utilized since before 1950 to enumerate the concentration of HDL particles and sort them by size with a specific volume of blood plasma. Larger HDL particles are carrying more cholesterol.
NMR measurements
Concentration and sizes of lipoprotein particles can be estimated using nuclear magnetic resonance
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...
fingerprinting.
Optimal total and large HDL concentrations
The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and being tracked in the MESA trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute.
The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles (the top quarter, >75%) and the highest concentrations of large HDL particles. Multiple additional measures, including LDL particle concentrations, small LDL particle concentrations, VLDL concentrations, estimations of insulin resistance
Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
Insulin is a horm ...
and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are routinely provided in clinical testing.
Increasing HDL levels
While higher HDL levels are correlated with lower risk of cardiovascular diseases, no medication used to increase HDL has been proven to improve health.[ As of 2017, numerous lifestyle changes and drugs to increase HDL levels were under study.][
HDL lipoprotein particles that bear apolipoprotein C3 are associated with increased, rather than decreased, risk for ]coronary heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
.
Diet and exercise
Certain changes in diet and exercise may have a positive impact on raising HDL levels:
* Decreased intake of simple carbohydrates.
* Aerobic exercise
Aerobic exercise, also known as cardio, is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. "Aerobic" is defined as "relating to, involving, or requiring oxygen", and refers to the use of ...
* Weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
* Avocado
The avocado, alligator pear or avocado pear (''Persea americana'') is an evergreen tree in the laurel family (Lauraceae). It is native to Americas, the Americas and was first domesticated in Mesoamerica more than 5,000 years ago. It was priz ...
consumption
* Magnesium
Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...
supplements raise HDL-C.
* Addition of soluble fiber
Dietary fiber (fibre in Commonwealth English) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition and can be grouped generally b ...
to diet
* Consumption of omega-3 fatty acids
Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their c ...
such as fish oil or flax oil
* Increased intake of unsaturated fat
An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fatty acid chain is Monounsaturated fat, monounsaturated if it contains one double bond, and polyunsaturated fat, polyunsaturated i ...
s
* Removal of trans fat
Trans fat is a type of unsaturated fat that occurs in foods. Small amounts of trans fats occur naturally, but large amounts are found in some processed foods made with partially hydrogenated oils. Because consumption of trans fats is associated ...
ty acids from the diet
Most saturated fats
A saturated fat is a type of fat in which the fatty acid chains have all single bonds between the carbon atoms. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone, and fatty acids that each contai ...
increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol.
Recreational drugs
HDL levels can be increased by smoking cessation
Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...
, or mild to moderate alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
intake.
Cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...
in unadjusted analyses, past and current cannabis use was not associated with higher HDL-C levels. A study performed in 4635 patients demonstrated no effect on the HDL-C levels (P=0.78) he mean (standard error) HDL-C values in control subjects (never used), past users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively
Exogenous anabolic androgenic steroids, particularly 17α-alkylated anabolic steroids and others administered orally, can reduce HDL-C by 50 percent or more. Other androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...
agonists such as selective androgen receptor modulators
Selective may refer to:
* Selective school, a school that admits students on the basis of some sort of selection criteria
** Selective school (New South Wales)
See also
* Selective breeding, the process of breeding for specific traits
* Select ...
can also lower HDL. As there is some evidence that the HDL reduction is caused by increased reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine.
Enhancing reverse cholesterol transport is considered a po ...
, it is unknown if AR agonists' HDL-lowering effect is pro- or anti- atherogenic.
Pharmaceutical drugs and niacin
Pharmacological therapy to increase the level of HDL cholesterol includes use of 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 choles ...
s and niacin
Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan.
Nicotinic acid is also a prescription medication. Amounts f ...
. Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids.
Niacin
Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan.
Nicotinic acid is also a prescription medication. Amounts f ...
(nicotinic acid, a form of vitamin B3
Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms, or vitamers: nicotinic acid (niacin), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within th ...
) increases HDL by selectively inhibiting hepatic diacylglycerol acyltransferase
Diglyceride acyltransferase (or ''O''-acyltransferase), DGAT, catalyzes the formation of triglycerides (triacylglycerols) from diacylglycerol and acyl-CoA. The reaction catalyzed by DGAT is considered the terminal and only committed step in the ...
2, reducing triglyceride
A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids.
Triglycerides are the main constituents of body fat in humans and other vertebrates ...
synthesis and 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, LDL, low-density ...
secretion through a receptor HM74 otherwise known as niacin receptor 2
Hydroxycarboxylic acid receptor 3 (HCA3), also known as niacin receptor 2 (NIACR2) and GPR109B, is a protein which in humans is encoded by the ''HCAR3'' gene. HCA3, like the other hydroxycarboxylic acid receptors HCA1 and HCA2, is a G protein- ...
and HM74A / GPR109A, niacin receptor 1.
Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%, making it the most powerful agent to increase HDL-cholesterol. A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events. Niacin products sold as "no-flush", ''i.e.'' not having side-effects such as "niacin flush
Flush may refer to:
Places
* Flush, Kansas, a community in the United States
Architecture, construction and manufacturing
* Flush cut, a type of cut made with a French flush-cut saw or diagonal pliers
* Flush deck, in naval architecture
* F ...
", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation. Both fibrates and niacin increase artery toxic homocysteine
Homocysteine (; symbol Hcy) is a non-proteinogenic α-amino acid. It is a homologous series, homologue of the amino acid cysteine, differing by an additional methylene bridge (). It is biosynthesized from methionine by the removal of its terminal ...
, an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 extended-release niacin (Niaspan) study was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke.
In contrast, while the use of statin
Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease.
Low-density lipoprotein (LDL) carriers of cholesterol play ...
s is effective against high levels of 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 ...
cholesterol, most have little or no effect in raising HDL cholesterol. Rosuvastatin
Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat dyslipidemia, abnormal lipids. It is recommended to be used with dietary changes, exer ...
and pitavastatin
Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins.
Pitavastatin is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis.
It was ...
, however, have been demonstrated to significantly raise HDL levels.
Lovaza has been shown to increase HDL-C. However, the best evidence to date suggests it has no benefit for primary or secondary prevention of cardiovascular disease.
The PPAR modulator GW501516 has shown a positive effect on HDL-C and an antiatherogenic where LDL is an issue. However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats.
See also
* Asymmetric dimethylarginine
* Cardiovascular disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
* Cholesteryl ester storage disease
Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) or Wolman disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an import ...
* Endothelium
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
* Lipid profile
A lipid profile or lipid panel is a Test panel, panel of blood tests used to find abnormalities in blood lipid ( such as cholesterol and triglycerides) concentrations. The results of this test can identify certain Inborn error of lipid metabolis ...
* Lysosomal acid lipase deficiency
Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) or Wolman disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an import ...
References
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