http://www.lactospore.com/glossary.htm
Atherogenic - Having the capacity to start or accelerate the process of atherogenesis (the
formation of lipid deposits in the arteries).
Atherosclerosis - The progressive narrowing and hardening of the arteries over time. This is
known to occur to some degree with aging, but other risk factors that accelerate this process have
been identified. These factors include: high cholesterol, high blood pressure, smoking, diabetes
and family history for atherosclerotic disease.
Hypercholesterolemia - Abnormal levels of serum cholesterol - Serum cholesterol > 200 mg/dL
(5.18 mmol/L). High risk 240 mg/dL (6.22 mmol/L) or more. High density lipoprotein fraction
of cholesterol (HDL) is protective, low density lipoprotein (LDL) is atherogenic
http://en.wikipedia.org/wiki/Hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia (British English) is the condition of
abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.[1] It is the most common
form of dyslipidemia (which also includes any decreased lipid levels).
Lipids (fat-soluble molecules) are transported in a protein capsule, and the size of that capsule, or
lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains
determines the fate of the particle and its influence on metabolism.
Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a
modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. In addition,
some forms may predispose to acute pancreatitis.
Hyperlipidemias may basically be classified as either familial (also called primary[2]) caused by specific
genetic abnormalities, or acquired (also called secondary)[2] when resulting from another underlying
disorder that leads to alterations in plasma lipid and lipoprotein metabolism.[2] Also, hyperlipidemia may
be idiopathic, that is, without known cause.
Hyperlipidemias may also be classified directly into which types of lipids are elevated, that is
hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of
Lipoprotein(a) may also be classified as a form of hyperlipidemia.
Familial (primary)
Familial hyperlipidemias are classified according to the Fredrickson classification which is based on
the pattern of lipoproteins on electrophoresis or ultracentrifugation.[3] It was later adopted by the World
Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the
different genes that may be partially responsible for some of these conditions. It remains a popular
system of classification, but is considered dated by many.
(Cat wording)
Hyperlipoproteinemia type I is a rare form of hyperlipoproteinemia associated with insufficient lipase.
Symptomatically, sufferers have abdominal pain from pancreatitis, a white appearance to the retina
given by lipid protein deposits, xanthomas on the skin, and enlargement of the spleen and pancreas.
Treatment is by diet control.
Type IIa, a more common form, is due to insufficient LDL receptors. Manifestations include
xanthelasmas (xanthoma found on the eyelids, a white or gray opaque ring in the corneal margin called
arcus senilis, and xanthomas found on the tendons. Treatment is by
1) A group of drugs called bile acid sequestrants such as Cholestyramine, Colesevelam, or Colestipol
may cause problems in the gastrointestinal tract (GI tract), such as constipation, diarrhea, and flatulence.
Some patients complain of the bad taste
2) Statins, which lower cholesterol by inhibiting enzymes which are used to produce cholesterol in the
liver. Lipitor, Crestor, and Zocor are among the more well known examples of statins. These lower
LDL, but have little effect to raise HDL. Unfortunately, statins have a number of adverse effects. They
can: raise liver enzymes, result in myalgias, muscle cramps, gastrointestinal symptoms, kidney
dysfunction, and polyneuropathy. Statins also interact with other cholesterol lowering medications and
with grapefruit which inhibits the metabolism of statins, keeping the serum level too high for too long .
3) Niacin, which reduces total cholesterol, triglycerides, and LDL’s while increasing the level of HDL’s.
Toxicity from too much niacin in the body can lead to flushing of the skin, itching, dry skin, and skin
rashes, though the effect is usually short-lived, lasting 15-30 minutes. High dose niacin can also elevate
blood sugar and cause more serum uric acid, exacerbating both diabetes and gout. Niacin is thought to
be teratogenic, causing birth defects in pregnant laboratory animals.
Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred
(2006). Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGrawHill. ISBN 0071422803.
Type IIb
http://en.wikipedia.org/wiki/Hypercholesterolemia
Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in
the blood.[1] It is not a disease but a metabolic derangement that can be secondary to many diseases and
can contribute to many forms of disease, most notably cardiovascular disease. It is closely related to the
terms "hyperlipidemia" (elevated levels of lipids) and "hyperlipoproteinemia" (elevated levels of
lipoproteins).[1]
Elevated cholesterol in the blood is due to abnormalities in the levels of lipoproteins, the particles that
carry cholesterol in the bloodstream. This may be related to diet, genetic factors (such as LDL receptor
mutations in familial hypercholesterolemia) and the presence of other diseases such as diabetes and an
underactive thyroid. The type of hypercholesterolemia depends on which type of particle (such as low
density lipoprotein) is present in excess.[1]
High cholesterol levels are treated with diets low in cholesterol, medications, and rarely with other
treatments including surgery (for particular severe subtypes). This[clarification needed] has also increased
emphasis on other risk factors for cardiovascular disease, such as high blood pressure.[1]
Signs and symptoms
Elevated cholesterol does not lead to specific symptoms unless it has been longstanding. Some types of
hypercholesterolemia lead to specific physical findings: xanthoma (deposition of cholesterol in patches
on the skin or in tendons), xanthelasma palpabrum (yellowish patches around the eyelids) and arcus
senilis (white discoloration of the peripheral cornea).[1]
Longstanding elevated hypercholesterolemia leads to accelerated atherosclerosis; this can express itself
in a number of cardiovascular diseases: coronary artery disease (angina pectoris, heart attacks), stroke
and short stroke-like episodes and peripheral vascular disease.[1][2][3]
There are a number of secondary causes for high cholesterol:
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
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Diabetes mellitus and metabolic syndrome
Kidney disease (nephrotic syndrome)
Hypothyroidism
Cushing's syndrome
Anorexia nervosa
Sleep deprivation
Zieve's syndrome
Family history
Antiretroviral drugs, like protease inhibitors and nucleoside reverse transcriptase inhibitors.
Diet
Body weight
Physical activity
Diet
While part of the circulating cholesterol originates from diet, and restricting cholesterol intake may
reduce blood cholesterol levels, there are various other links between the dietary pattern and cholesterol
levels. The American Heart Association compiles a list of the acceptable and unacceptable foods for
those who are diagnosed with hypercholesterolemia.
Dietary changes can potentially be very strong: when a group of Tarahumara Indians from Mexico with
no obesity or cholesterol problems were exposed to a Western diet, their risk profile worsened
significantly, with cholesterol levels rising over thirty percent.[4]
Carbohydrates
Evidence is accumulating that eating more carbohydrates - especially simpler, more refined
carbohydrates - increases levels of triglycerides in the blood, lowers HDL, and may shift the LDL
particle distribution pattern into unhealthy atherogenic patterns.[5]
Trans fats
An increasing number of researchers are suggesting that a major dietary risk factor for cardiovascular
diseases is trans fatty acids, and in the US the FDA has revised food labeling requirements to include
listing trans fat quantities.[6]
Genetics
Genetic abnormalities is in some cases completely responsible for hypercholesterolemia, such as in
familial hypercholesterolemia where there is one or more genetic mutations in, for example, the LDL
receptor.
Even when there is no single responsible mutation to explain hypercholesterolemia, genetic
predisposition still plays a major role, potentially adding to lifestyle factors and multiplying the risk of
late complications. Multiple genes are involved, and hypercholesterolemia where there is probably a
genetic predisposition is called polygenic hypercholesterolemia. The involved genes have yet to be
discovered.[7]
Screening
The U.S. Preventive Services Task Force (USPSTF) has evaluated screening for hypercholesterolemia.
They strongly recommends that clinicians routinely screen men aged 35 years and older and women
aged 45 years and older for lipid disorders and treat abnormal lipids in people who are at increased risk
of coronary heart disease (level A recommendation). They also recommend that clinicians routinely
screen younger adults (men aged 20 to 35 years and women aged 20 to 45 years) for lipid disorders if
they have other risk factors for coronary heart disease (level B recommendation).[10][11]
Treatment
A summary of treatment for both primary prevention[12] and secondary prevention.[13] has been
published. Two factors have been put forward for consideration when choosing therapy are the patient's
risk of coronary disease and their lipoprotein pattern.
1. Risk of coronary disease. To calculate the benefit of treatment, there are two online calculators
that can estimate baseline risk.[14][15] Combining the baseline risk with the relative risk reduction
of a treatment can lead to the absolute risk reduction of number needed to treat. For example, one
of the calculators projects that a patient had a 10% risk of coronary disease over ten years. As
noted below, the relative risk reduction of a statin is 30%. Thus, after 4–7 years of treatment with
a statin, a patient's risk will drop to 7%. This equates to an absolute risk reduction of 3%, or a
number needed to treat of 33. Thirty three such patients must be treated for 4–7 years for one to
benefit.
2. Lipoprotein patterns. (See hyperlipoproteinemia for details) The treatment depends on the type
of hypercholesterolemia. Clinical trials, starting in the 1970s, have repeatedly and increasingly
found that normal cholesterol values do not necessarily reflect healthy cholesterol values. This
has increasingly lead to the newer concept of dyslipidemia, despite normo-cholesterolemia. Thus
there has been increasing recognition of the importance of "lipoprotein subclass analysis" as an
important approach to better understand and change the connection between cholesterol transport
and atherosclerosis progression. Fredrickson Types IIa and IIb can be treated with diet, statins
(most prominently rosuvastatin, atorvastatin, simvastatin, or pravastatin), cholesterol absorption
inhibitors (ezetimibe), fibrates (gemfibrozil, bezafibrate, fenofibrate or ciprofibrate), vitamin B3
(niacin), bile acid sequestrants (colestipol, cholestyramine), LDL apheresis and in hereditary
severe cases liver transplantation.
Diet
In strictly controlled surroundings, such as a hospital ward dedicated to metabolism problems, a diet can
reduce cholesterol levels by 15%. In practice, dietary advice can provide a modest decrease in
cholesterol levels and may be sufficient in the treatment of mildly elevated cholesterol.[16]
Medications
While statins are effective in decreasing mortality in those who have had previous cardiovascular
disease there is not a mortality benefit in those at high-risk but without prior cardiovascular disease.[17]
No studies as of 2010 show improved clinical outcomes in children with high cholesterol even though
statins decrease cholesterol levels.[18]
Clinical practice guidelines
Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The
American College of Physicians has addressed hypercholesterolemia in patients with diabetes.[19] Their
four recommendations are:
1. Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and
morbidity for all patients (both men and women) with known coronary artery disease and type 2
diabetes.
2. Statins should be used for primary prevention against macrovascular complications in patients
(both men and women) with type 2 diabetes and other cardiovascular risk factors.
3. Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at
least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d;
pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another
statin").[20]
4. For those patients with type 2 diabetes who are taking statins, routine monitoring of liver
function tests or muscle enzymes is not recommended except in specific circumstances.
The National Cholesterol Education Program revised their guidelines;[21] however, their 2004 revisions
have been criticized for use of nonrandomized, observational data.[22]
In the UK, the National Institute for Health and Clinical Excellence (NICE) has made recommendations
for the treatment of elevated cholesterol levels, published in 2008.[23]
Alternative medicine
A survey by the National Center for Complementary and Alternative Medicine focused on who used
complementary and alternative medicine (CAM), what was used, and why it was used in the United
States by adults age 18 years and over during 2002. According to this survey, CAM was used to treat
cholesterol by 1.1% of U.S. adults who used CAM during 2002.[24] Consistent with previous studies, this
study found that the majority of individuals (i.e., 54.9%) used CAM in conjunction with conventional
medicine (page 6).[25]
A review of 84 clinical trials with phytosterols and/or phytostanols reported an average of 8.8%
lowering of LDL-cholesterol with a mean daily intake of 2.15 grams/day, administered 2-3 times a day
with meals. The dose:response figure shows that more than half of the response is achieved once intake
is more than 1.0 g/day.[26] In 2000 the Food and Drug Administration approved a Qualified Health Claim
for 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 grams/day of either esterified or non-esterified ("free")
phytosterols or phytostanols divided over two doses per day. Some researchers, however, are concerned
about diet supplementation with plant sterol esters and draw attention to significant safety issues. This is
why Health Canada, the federal department responsible for helping Canadians maintain and improve
their health, has not allowed these foods to be sold in Canada.[27]
http://en.wikipedia.org/wiki/Cholesterol
Cholesterol
Cholesterol is a waxy steroid metabolite found in the cell membranes and transported in the blood
plasma of all animals.[2] It is an essential structural component of mammalian cell membranes, where it
is required to establish proper membrane permeability and fluidity. In addition, cholesterol is an
important component for the manufacture of bile acids, steroid hormones, and fat-soluble vitamins
including Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol is the principal sterol
synthesized by animals, but small quantities are synthesized in other eukaryotes, such as plants and
fungi. It is almost completely absent among prokaryotes, which include bacteria.[3] Although cholesterol
is an important and necessary molecule for animals, a high level of serum cholesterol is an indicator for
diseases such as heart disease.
Since cholesterol is essential for all animal life, it is primarily synthesized from simpler substances
within the body. However, high levels in blood circulation, depending on how it is transported within
lipoproteins, are strongly associated with progression of atherosclerosis. For a person of about 68 kg
(150 pounds), typical total body cholesterol synthesis is about 1 g (1,000 mg) per day, and total body
content is about 35 g. Typical daily additional dietary intake, in the United States is 200–300 mg[citation
needed]
. The body compensates for cholesterol intake by reducing the amount synthesized.
Cholesterol is recycled. It is excreted by the liver via the bile into the digestive tract. Typically about
50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.
Phytosterols can compete cholesterol reabsorption in intestinal tract back into the intestinal lumen for
elimination.
Cholesterol is required to build and maintain membranes; it regulates membrane fluidity over the range
of physiological temperatures. Within the cell membrane, cholesterol also functions in intracellular
transport, cell signaling and nerve conduction.
Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver,
cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which
solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fatsoluble vitamins, Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol is an important
precursor molecule for the synthesis of Vitamin D and the steroid hormones, including the adrenal gland
hormones cortisol and aldosterone as well as the sex hormones progesterone, estrogens, and
testosterone, and their derivatives.
Some research indicates that cholesterol may act as an antioxidant.
Dietary Sources
Animal fats are complex mixtures of triglycerides, with lesser amounts of phospholipids and cholesterol.
As a consequence, all foods containing animal fat contain cholesterol to varying extents.[9] Major dietary
sources of cholesterol include cheese, egg yolks, beef, pork, poultry, and shrimp.[10]
Human breast milk also contains significant quantities of cholesterol.[11]
The amount of cholesterol present in plant-based food sources is generally much lower than animal
based sources.[10][12] In addition, plant products such as flax seeds and peanuts contain cholesterol-like
compounds called phytosterols, which are suggested to help lower serum cholesterol levels.[13]
Total fat intake, especially saturated fat and trans fat,[14] plays a larger role in blood cholesterol than
intake of cholesterol itself. Saturated fat is present in full fat dairy products, animal fats, several types of
oil and chocolate. Trans fats are typically derived from the partial hydrogenation of unsaturated fats,
and, in contrast to other types of fat, do not occur in significant amounts in nature. Research supports a
recommendation to minimize or eliminate trans fats from the diet due to their adverse health effects. [15]
Trans fat is most often encountered in margarine and hydrogenated vegetable fat, and consequently in
many fast foods, snack foods, and fried or baked goods.
A change in diet in addition to other lifestyle modifications may help reduce blood cholesterol. Avoiding
animal products may decrease the cholesterol levels in the body not only by reducing the quantity of
cholesterol consumed but also by reducing the quantity of cholesterol synthesized. Those wishing to
reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily
calories from saturated fat and less than 200 mg of cholesterol per day.
The view that a change in diet (to be specific, a reduction in dietary fat and cholesterol) can lower blood
cholesterol levels,[17] and thus reduce the likelihood of development of, among others, coronary artery
disease (CAD) leading to coronary heart disease (CHD) has been challenged. An alternative view is that
any reductions to dietary cholesterol intake are counteracted by the organs such as the liver, which will
increase or decrease production of cholesterol to keep blood cholesterol levels constant.[18] Another view
is that although saturated fat and dietary cholesterol also raise blood cholesterol, these nutrients are not
as effective at doing this as is animal protein.
About 20–25% of total daily cholesterol production occurs in the liver; other sites of high synthesis rates
include the intestines, adrenal glands, and reproductive organs.
Cholesterol is only slightly soluble in water; it can dissolve and travel in the water-based bloodstream at
exceedingly small concentrations. Since cholesterol is insoluble in blood, it is transported in the
circulatory system within lipoproteins. In addition to providing a soluble means for transporting
cholesterol through the blood, lipoproteins have cell-targeting signals that direct the lipids they carry to
certain tissues. For this reason, there are several types of lipoproteins within blood called, in order of
increasing density, chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density
lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The more
cholesterol and less protein a lipoprotein has the less dense it is. The cholesterol within all the various
lipoproteins is identical, although some cholesterol is carried as the "free" alcohol and some is carried as
fatty acyl esters referred to as cholesterol esters. However, the different lipoproteins contain
apolipoproteins, which serve as ligands for specific receptors on cell membranes. In this way, the
lipoprotein particles are molecular addresses that determine the start- and endpoints for cholesterol
transport.
The American Heart Association provides a similar set of guidelines for total (fasting) blood cholesterol
levels and risk for heart disease:
Level mg/dL
Interpretation
< 200
Desirable level corresponding to lower risk for heart disease
200–240
Borderline high risk
> 240
High risk
However, as today's testing methods determine LDL ("bad") and HDL ("good") cholesterol separately,
this simplistic view has become somewhat outdated. (see articles below)
http://en.wikipedia.org/wiki/High-density_lipoprotein
HDL
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins which, in order of
sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL and HDL, which enable lipids like
cholesterol and triglycerides to be transported within the water-based bloodstream. In healthy
individuals, about thirty percent of blood cholesterol is carried by HDL.[1]
Blood tests typically report HDL-C, the amount of cholesterol contained in HDL particles. It is often
contrasted with low density or LDL cholesterol or LDL-C. HDL particles are able to remove cholesterol
from atheroma[citation needed] within arteries and transport it back to the liver for excretion or re-utilization,
which is the main reason why the cholesterol carried within HDL particles, termed HDL-C, is
sometimes called "good cholesterol". Those with higher levels of HDL-C seem to have fewer problems
with cardiovascular diseases, while those with low HDL-C cholesterol levels (less than 40 mg/dL or
about 1 mmol/L) have increased rates for heart disease.[1][citation needed]. However, see the clarifications
below about estimating HDL particles via cholesterol content versus directly measuring HDL particles
and function. Additionally, those few individuals producing an abnormal, apparently more efficient,
HDL ApoA1 protein variant called ApoA-1 Milano, have low measured HDL-C levels yet very low
rates of cardiovascular events even with high blood cholesterol values[citation needed].
Structure and function
HDL is the smallest of the lipoprotein particles. They are the densest because they contain the highest
proportion of protein. Their most abundant apolipoproteins are apo A-I and apo A-II.[2] The liver
synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble
cholesterol-free flattened spherical lipoprotein particles. They 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 making the newly synthesized HDL spherical. They increase in size as
they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules
from cells and other lipoproteins, for example by the interaction with the ABCG1 transporter and the
phospholipid transport protein (PLTP).
HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals, ovary, and
testes by 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 against cholesteryl esters of HDL. As the result, VLDLs
are processed to LDL, which are removed from the circulation by the LDL receptor pathway. The
triglycerides are not stable in HDL, but degraded by hepatic lipase 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 and, hence, intestine either directly or
indirectly after conversion into bile acids. Delivery of HDL cholesterol to adrenals, ovaries, and testes is
important for the synthesis of steroid hormones.
Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid-laden
macrophages of atherosclerotic arteries, termed foam cells, to the liver for secretion into the bile. This
pathway has been termed reverse cholesterol transport and is considered as the classical protective
function of HDL toward atherosclerosis.
However, HDL carries many lipid and protein species, several of which have very low concentrations
but are biologically very active. For example, HDL and their protein and lipid constituents help to
inhibit oxidation, inflammation, activation of the endothelium, coagulation, and platelet aggregation. All
these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet
known what are the most important.
In the stress response, serum amyloid A, which is one of the acute-phase proteins and an apolipoprotein,
is under the stimulation of cytokines (IL-1, IL-6), and cortisol produced in the adrenal cortex 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.
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.[3] This ratio of large HDL to total HDL
particles varies widely and is measured only by more sophisticated lipoprotein assays using either
electrophoresis (the original method developed in the 1970s) or newer NMR spectroscopy methods (See
also: NMR and spectroscopy), developed in the 1990s
Men tend to have noticeably lower HDL levels, with smaller size and lower cholesterol content, than
women. Men also have an increased incidence of atherosclerotic heart disease.
Epidemiology
Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective
value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low
concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for
atherosclerotic diseases.
Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of
heart disease increases 10-fold as the HDL varies from high to low[citation needed]. On the converse,
however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high[citation needed].
Even people with very low LDL levels are exposed to increased risk if their HDL levels are not high
enough.[4]
American Heart Association and NIH recommend the following guidelines for fasting HDL ranges.
Level (mg/dL…or g/L)
<40 for men, <50 for
women
40–59
>60
Interpretation
Low HDL cholesterol, heightened risk for heart disease
Medium HDL level
High HDL level, optimal condition considered
protective against heart disease
Raising HDL
Diet and lifestyle
Certain changes in lifestyle can have a positive impact on raising HDL levels:[15]

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





Aerobic exercise[16]
Weight loss[17]
Smoking cessation[17]
Removing trans fatty acids from the diet[18]
Mild to moderate alcohol intake[17] HDL transports cholesterol to the liver and cholesterol is
known to have a protective effect on the cell membrane.[citation needed] It is likely that this reflects
the liver's need for more cholesterol to protect itself from the alcohol.(see Fatty liver)[19]
Adding soluble fiber to diet[citation needed]
Using supplements such as omega 3 fish oil[20] or flax oil[citation needed]
Increasing intake of cis-unsaturated fats[21] and cholesterol, decreasing intake of trans-fats.
Avoiding supplements that contain omega 6 (Omega 6 reduces cholesterol but does not
discriminate between good and bad cholesterol) as well as limiting foods high in omega 6
(tilapia, most vegetable oils, nuts)[citation needed]
A high-fat, adequate-protein, low-carbohydrate ketogenic diet may have similar response to taking
niacin as described below (lowered LDL and increased HDL) through beta-hydroxybutyrate coupling
the Niacin receptor 1.[22]
Drugs
Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin.
Fibrates, however, have shown that they have no effect on overall deaths from all causes, despite their
effects on lipids.[23]
Niacin (B3), increases HDL by selectively inhibiting hepatic Diacylglycerol acyltransferase 2, reducing
triglyceride synthesis and VLDL secretion through a receptor HM74[24] otherwise known as Niacin
receptor 2 and HM74A / GPR109A,[22] Niacin receptor 1.
Pharmacologic (1- to 3-gram) doses increase HDL levels by 10–30%,[25] making it the most powerful
agent to increase HDL-cholesterol.[26][27] A randomized clinical trial demonstrated that treatment with
niacin can significantly reduce atherosclerosis progression and cardiovascular events.[28] However,
niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush", do not 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.[29] Both fibrates and niacin
increase artery toxic homocysteine, an effect that can be counteracted by also consuming a multivitamin
with relatively high amounts of the B-vitamins.[citation needed]
In contrast, while the use of statins is effective against high levels of LDL cholesterol, it has little or no
effect in raising HDL cholesterol.[26]
Torcetrapib, a drug developed by Pfizer to raise HDL by inhibition of cholesteryl ester transfer protein
(CETP), was terminated after a greater percentage of patients treated with torcetrapib-Lipitor
combination died compared with patients treated with Lipitor alone. Merck is currently researching a
similar molecule called anacetrapib
http://en.wikipedia.org/wiki/Low-density_lipoprotein
LDL
Low-density lipoprotein (LDL) is one of the five major groups of lipoproteins, which in order of size,
largest to smallest, are chylomicrons, VLDL, IDL, LDL and HDL, that enable lipids like cholesterol and
triglycerides to be transported within the water-based bloodstream. Blood tests typically report LDL-C,
the amount of cholesterol contained in LDL. Medically, mathematically calculated estimates of LDL-C
are commonly used to estimate how much low density lipoproteins are driving progression of
atherosclerosis. Direct LDL measurements are also available and better reveal individual issues but are
less often promoted or done due to slightly higher costs and being available from only a couple of
laboratories in the United States. In 28 March 2008, as part of a joint consensus statement by the ADA
and ACC, direct LDL particle measurement by NMR was recognized as superior for assessing
individual risk of cardiovascular events.[1] Since higher levels of LDL particles promote health problems
and cardiovascular disease, they are often called the bad cholesterol particles, (as opposed to HDL
particles, which are frequently referred to as good cholesterol or healthy cholesterol particles).[2]
LDL particles vary in size and density, and studies have shown that a pattern that has more small dense
LDL particles, called Pattern B, equates to a higher risk factor for coronary heart disease (CHD) than
does a pattern with more of the larger and less dense LDL particles (Pattern A). This is because the
smaller particles are more easily able to penetrate the endothelium. Pattern I, for intermediate, indicates
that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm).
The correspondence between Pattern B and CHD has been suggested by some in the medical community
to be stronger than the correspondence between the LDL number measured in the standard lipid profile
test. Tests to measure these LDL subtype patterns have been more expensive and not widely available,
so the common lipid profile test has been used more commonly.
There has also been noted a correspondence between higher triglyceride levels and higher levels of
smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the larger,
less dense LDL.[4][5]
With continued research, decreasing cost, greater availability and wider acceptance of other lipoprotein
subclass analysis assay methods, including NMR spectroscopy,[6] research studies have continued to
show a stronger correlation between human clinically obvious cardiovascular event and quantitativelymeasured particle concentrations.
Because LDL particles can also transport cholesterol into the artery wall, retained there by arterial
proteoglycans and attract macrophages which engulf the LDL particles and start the formation of
plaques, increased levels are associated with atherosclerosis.
LDL particles pose a risk for cardiovascular disease when they invade the endothelium and becomes
oxidized, since the oxidized forms are more easily retained by the proteoglycans. A complex set of
biochemical reactions regulates the oxidation of LDL particles, chiefly stimulated by presence of
necrotic cell debries [6] and free radicals in the endothelium.
Lowering LDL
The mevalonate pathway serves as the basis for the biosynthesis of many molecules, including
cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) is
an essential component in the pathway.
Pharmaceutical
Statins (HMG-CoA reductase inhibitors) reduce high levels of LDL particles. Statins inhibit the enzyme
HMG-CoA reductase in cells, the rate-limiting step of cholesterol synthesis. To compensate for the
decreased cholesterol availability, synthesis of hepatic LDL receptors is increased, resulting in an
increased clearance of LDL particles from the blood.
Ezetimibe reduces intestinal absorption of cholesterol, thus can powerfully augment the LDL particle
concentrations when combined with any of the statins.
Niacin (B3), lowers LDL by selectively inhibiting hepatic diacyglycerol acyltransferase 2, reducing
triglyceride synthesis and VLDL secretion through a receptor HM74[9] and HM74A or GPR109A.[10]
Clofibrate is effective at lowering cholesterol levels, but has been associated with significantly increased
cancer and stroke mortality, despite lowered cholesterol levels.[11] Other, more recently developed and
tested fibrates, e.g. fenofibric acid [7] have had a better track record and are primarily promoted for
lowering VLDL particles (triglycerides), not LDL particles, yet can help some in combination with other
strategies.
Some Tocotrienols, especially d- and ?-tocotrienols, are being promoted as statin alternative nonprescription agents to treat high cholesterol, having been shown in vitro to have an effect. In
particular, ?-tocotrienol appears to be another HMG-CoA reductase inhibitor and can reduce cholesterol
production.[12] As with statins, this decrease in intra-hepatic (liver) LDL levels may induce hepatic LDL
receptor up-regulation, also decreasing plasma LDL levels. As always, a key issue is how the benefits
and complications of such agents will compare with the statins, molecular tools which have been
analyzed, since the mid-1970s, in large numbers of human research and clinical trials.
Dietary
The most effective approach has been minimizing visceral (in addition to total) body fat stores. Visceral
fat, which is more metabolically active than subcutaneous fat, has been found to produce many
enzymatic signals, e.g. resistin, which increase insulin resistance and circulating VLDL particle
concentrations, thus both increasing LDL particle concentrations and accelerating the development of
Diabetes Mellitus.
Insulin induces HMG-CoA reductase activity, whereas glucagon downregulates it.[13] While glucagon
production is stimulated by dietary protein ingestion, insulin production is stimulated by dietary
carbohydrate. The rise of insulin is, in general, determined by the digestion of carbohydrates into
glucose and subsequent increase in serum glucose levels. In non-diabetics, glucagon levels are very low
when insulin levels are high; however, those who have become diabetic no longer suppress glucagon
output after eating.
A ketogenic diet may have similar response to taking niacin (lowered LDL and increased HDL) through
beta-hydroxybutyrate, a ketone body, coupling the niacin receptor (HM74A).[10]
Lowering the blood lipid concentration of triglycerides helps lower the concentration of LDL particles,
because VLDL particles converted in the bloodstream into LDL particles.[vague]
Fructose, a component of sucrose as well as high-fructose corn syrup, upregulates hepatic VLDL
synthesis.[14]
Importance of antioxidants
Because LDL particles appear to be harmless until within the blood vessel walls and oxidized by free
radicals,[15] it is postulated that ingesting antioxidants and minimizing free radical exposure may reduce
LDL's contribution to atherosclerosis, though results are not conclusive.[16]
American Heart Association and NIH recommend the following guidelines for fasting LDL ranges and
estimated risk of heart disease. Current as of 2005
Level
(mg/dL…or
g/L)
25 to <50
<70
<100
100 to 129
130 to 159
160 to 199
>200
Interpretation
Optimal LDL cholesterol, levels in healthy young children before onset of
atherosclerotic plaque in heart artery walls
Optimal LDL cholesterol, corresponding to lower rates of progression, promoted as a
target option for those known to clearly have advanced symptomatic cardiovascular
disease
Optimal LDL cholesterol, corresponding to lower, but not zero, rates for symptomatic
cardiovascular disease events
Near optimal LDL level, corresponding to higher rates for developing symptomatic
cardiovascular disease events
Borderline high LDL level, corresponding to even higher rates for developing
symptomatic cardiovascular disease events
High LDL level, corresponding to much higher rates for developing symptomatic
cardiovascular disease events
Very high LDL level, corresponding to highest increased rates of symptomatic
cardiovascular disease events
http://en.wikipedia.org/wiki/Triglyceride
Triglycerides
A triglyceride is an ester derived from glycerol and three fatty acids.[1] It is the main constituent of
vegetable oil and animal fats. Triglycerides are formed by combining glycerol with three molecules of
fatty acid.
The enzyme pancreatic lipase acts at the ester bond, hydrolysing the bond and "releasing" the fatty acid.
In triglyceride form, lipids cannot be absorbed by the duodenum. Fatty acids, monoglycerides (one
glycerol, one fatty acid) and some diglycerides are absorbed by the duodenum, once the triglycerides
have been broken down.
Triglycerides, as major components of very-low-density lipoprotein (VLDL) and chylomicrons, play an
important role in metabolism as energy sources and transporters of dietary fat. They contain more than
twice as much energy (9 kcal/g or 38 kJ/g ) as carbohydrates and proteins. In the intestine, triglycerides
are split into monoacylglycerol and free fatty acids in a process called lipolysis, with the secretion of
lipases and bile, which are subsequently moved to absorptive enterocytes, cells lining the intestines. The
triglycerides are rebuilt in the enterocytes from their fragments and packaged together with cholesterol
and proteins to form chylomicrons. These are excreted from the cells and collected by the lymph system
and transported to the large vessels near the heart before being mixed into the blood. Various tissues can
capture the chylomicrons, releasing the triglycerides to be used as a source of energy. Fat and liver cells
can synthesize and store triglycerides. When the body requires fatty acids as an energy source, the
hormone glucagon signals the breakdown of the triglycerides by hormone-sensitive lipase to release free
fatty acids. As the brain cannot utilize fatty acids as an energy source (unless converted to a ketone), the
glycerol component of triglycerides can be converted into glucose, via gluconeogenesis, for brain fuel
when it is broken down. Fat cells may also be broken down for that reason, if the brain's needs ever
outweigh the body's.
Triglycerides cannot pass through cell membranes freely. Special enzymes on the walls of blood vessels
called lipoprotein lipases must break down triglycerides into free fatty acids and glycerol. Fatty acids
can then be taken up by cells via the fatty acid transporter (FAT).
In the human body, high levels of triglycerides in the bloodstream have been linked to atherosclerosis,
and, by extension, the risk of heart disease and stroke. However, the relative negative impact of raised
levels of triglycerides compared to that of LDL:HDL ratios is as yet unknown. The risk can be partly
accounted for by a strong inverse relationship between triglyceride level and HDL-cholesterol level.
The American Heart Association has set guidelines for triglyceride levels:
Level
(mg/dL…or
g/L)
<150
150-199
200-499
>500
Interpretation
Normal range, low risk
Borderline high
High
Very high: high risk
Please note that this information is relevant to triglyceride levels as tested after fasting 8 to 12 hours.
Triglyceride levels remain temporarily higher for a period of time after eating.
Diets high in carbohydrates, with carbohydrates accounting for more than 60% of the total caloric
intake, can increase triglyceride levels.[3] Of note is how the correlation is stronger for those with higher
BMI (28+) and insulin resistance (more common among overweight and obese) is a primary suspect
cause of this phenomenon of carbohydrate-induced hypertriglyceridemia.[4]
There is evidence that carbohydrate consumption causing a high glycemic index can cause insulin
overproduction and increase triglyceride levels in women.[5]
Adverse changes associated with carbohydrate intake, including triglyceride levels, are stronger risk
factors for heart disease in women than in men.[6]
Triglyceride levels are also reduced by exercise, omega-3 fatty acids from fish, flax seed oil, and other
sources. Recommendation in the U.S. is that one ingest up to 3 grams a day of such oils. It has been
found that residents in Western countries do not ingest sufficient quantity of food with omega-3. In
Europe, the recommendation is for up to 2 grams. However, omega-3 consumption should be balanced
with omega-6 fatty acids, in a ω-6/ω-3 ratio between 1:1 and 4:1 (i.e., no more than four grams omega-6
for every one of omega-3).[7][8]
Carnitine has the ability to lower blood triglyceride levels.[9] In some cases, fibrates have been used to
bring down triglycerides substantially.[10]
Heavy use of alcohol can elevate triglycerides levels.
http://en.wikipedia.org/wiki/Saturated_fat
Saturated Fats
Saturated fat is fat that consists of triglycerides containing only saturated fatty acid radicals. There are
many kinds of naturally occurring saturated fatty acids, which differ by the number of carbon atoms,
ranging from 3 carbons (propionic acid) to 36 (Hexatriacontanoic acid). Saturated fatty acids have no
double bonds between the carbon atoms of the fatty acid chain and are thus fully saturated with
hydrogen atoms.
Fat that occurs naturally in tissue contains varying proportions of saturated and unsaturated fat.
Examples of foods containing a high proportion of saturated fat include dairy products (especially cream
and cheese but also butter and ghee); animal fats such as suet, tallow, lard and fatty meat; coconut oil,
cottonseed oil, palm kernel oil, chocolate, and some prepared foods.[1]
Serum saturated fatty acid is generally higher in smokers, alcohol drinkers and obese people.
Cardiovascular diseases
In 2010, a meta-analysis of prospective cohort studies including 348,000 subjects found no statistically
significant relationship between cardiovascular disease and dietary saturated fat.[8][9] However, the
authors noted that randomized controlled clinical trials in which saturated fat was replaced with
polyunsaturated fat observed a reduction in heart disease, and that the ratio between polyunsaturated fat
and saturated fat may be a key factor.[8] In 2009, a systematic review of prospective cohort studies or
randomized trials concluded that there was "insufficient evidence of association" between intake of
saturated fatty acids and coronary heart disease, and pointed to strong evidence for protective factors
such as vegetables and a Mediterranean diet and harmful factors such as trans fats and foods with a high
glycemic index.[10]. Pacific island populations who obtain 30-60% of their total caloric intake from fully
saturated coconut fat have low rates of cardiovascular disease.[11]
An evaluation of data from Harvard Nurses' Health Study found that "diets lower in carbohydrate and
higher in protein and fat are not associated with increased risk of coronary heart disease in women.
When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of
coronary heart disease."[12]
Mayo Clinic highlighted oils that are high in saturated fats include coconut, palm oil and palm kernel
oil. Those of lower amounts of saturated fats, and higher levels of unsaturated (preferably
monounsaturated) fats like olive oil, peanut oil, canola oil, avocados, safflower, corn, sunflower, soy and
cottonseed oils are generally healthier.[13] However, high intake of saturated dairy fat does not appear to
increase the risk of cardiovascular disease.[14]
8. ^ a b Siri-Tarino PW, Sun Q, Hu FB, Krauss RM (March 2010). "Meta-analysis of prospective
cohort studies evaluating the association of saturated fat with cardiovascular disease". The
American Journal of Clinical Nutrition 91 (3): 535–46. doi:10.3945/ajcn.2009.27725.
PMID 20071648
9. ^ Siri-Tarino PW, Sun Q, Hu FB, Krauss RM (March 2010). "Saturated fat, carbohydrate, and
cardiovascular disease". The American Journal of Clinical Nutrition 91 (3): 502–9.
doi:10.3945/ajcn.2008.26285. PMID 20089734
10. Mente A, de Koning L, Shannon HS, Anand SS (April 2009). "A systematic review of the
evidence supporting a causal link between dietary factors and coronary heart disease". Arch.
Intern. Med. 169 (7): 659–69. doi:10.1001/archinternmed.2009.38. PMID 19364995. Free fulltext
A study published in 2001 found higher levels of monounsaturated fatty acids (especially oleic acid) in
the erythrocyte membranes of postmenopausal women who developed breast cancer.[15] However,
another study showed a direct relation between very high consumption of omega-6 polyunsaturated fats
and breast cancer in postmenopausal women.[16]
Some researchers have indicated that serum myristic acid[17][18] and palmitic acid[18] and dietary
myristic[19] and palmitic[19] saturated fatty acids and serum palmitic combined with alpha-tocopherol
supplementation[17] are associated with increased risk of prostate cancer in a dose-dependent manner.
These associations may, however, reflect differences in intake or metabolism of these fatty acids
between the precancer cases and controls, rather than being an actual cause.[18]
A prospective study of data from the NIH-AARP Diet and Health Study positively correlated saturated
fat intake with cancer of the small intestine.[20]
A 2004 statement released by the Centers for Disease Control (CDC) determined that "Americans need
to continue working to reduce saturated fat intake…"[21] Additionally, reviews by the American Heart
Association led the Association to recommend reducing saturated fat intake to less than 7% of total
calories according to its 2006 recommendations.[22][23] This concurs with similar conclusions made by
the World Health Organization (WHO) and the US Department of Health and Human Services, both of
which determined that reduction in saturated fat consumption would positively affect health and reduce
the prevalence of heart disease.[24][25][26]
The World Health Organization (WHO) has concluded that saturated fats negatively affect cholesterol
profiles, predisposing individuals to heart disease, and recommends avoiding saturated fats in order to
reduce the risk of a cardiovascular disease.[27][28]
Dr German and Dr Dillard of University of California and Nestle Research Center in Switzerland, in
their 2004 review, pointed out that "no lower safe limit of specific saturated fatty acid intakes has been
identified". No randomized clinical trials of low-fat diets or low-saturated fat diets of sufficient duration
have been carried out. The influence of varying saturated fatty acid intakes against a background of
different individual lifestyles and genetic backgrounds should be the focus in future studies.