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| | Each day application of a moisturizer will keep psoriasis at bay. However, Shark Cartilage has been used successfully for [http://www.dominionradio.info/sitemap/ treating Psoriasis], in particular AE 941 a shark cartilage extract. Mahonia aquifolium offers real hope to thousands of Psoriasis sufferers and is, without doubt, the safest & most effective herbal psoriasis treatment available. Keep way from eggs and animal fats as much as you can. An autoimmune disease, it is frequently hereditary, and has been linked to obesity, heart disease and diabetes. <br><br>People who suffer from the streptococcal infection are likely to get infected with the psoriasis. In some people it has no physically visible symptoms. This might be the reason why drinking causes major psoriasis flare ups. I recommend that you try the mentioned psoriasis scalp treatment oils and see which one gives you the best results. Most agree that those with exceptionally high IQs are much more likely to be afflicted with psoriasis. <br><br>What is the difference between psoriasis and eczema. ) starting to slip in some of the more luxurious ingredients that women have been enjoying the benefits of for years. It challenges the longstanding thinking about psoriasis. A few people have reported good results with the use of Coal Tar hair shampoos, however, these forms of products do not work successfully for all and might stain or even discolor the head of hair. Could it have anything to do with the overall toxicity level of the body. <br><br>With any recurring signs of psoriasis there is the handful of common inner body triggers that seems to be related to the skin disorder flare-ups. Later dermatology was enriched by new facts about the zest of the disease. One thing that may perhaps be indispensable is for you to have a high quality air filter installed in your home, or at least in the area where you sleep. This problem causes T cells to start treating healthy skin cells as if they were a wound that needed healing: they tell the body to create more skin cells, because they think this is needed to prevent the wound from getting infected. When the burning itch arrives, without even thinking about it, the sufferer will scratch it. <br><br>Castile soap is a type of natural soap made exclusively from vegetable oils, such as olive, coconut and jojoba oil. This can aid in reducing anxiety and can lift a person. Eating plan prepares with fish oil and also vegetable might boost the extent of the ailment. These are very simple ingredients that make the inflammation and also the itchy skin absolutely typical and you'd by no means really feel discomfort or under no circumstances feel the urge to scratch your skin regularly. A few may appear to work mainly because psoriasis is characterized by flare-ups and remissions. |
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| {{external links|date=April 2013}}
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| '''Low-density lipoprotein''' ('''LDL''') is one of the five major groups of [[lipoprotein]]s, which, in order of [[molecular size]], largest to smallest, are [[chylomicron]]s, [[very low-density lipoprotein]] (VLDL), [[intermediate-density lipoprotein]] (IDL), '''LDL''', and [[high-density lipoprotein]] (HDL). Lipoprotein molecules enable the transportation of [[lipids]] (fats), such as [[cholesterol]], [[phospholipids]], and [[triglycerides]], within the water around cells ([[extracellular fluid]]), including the [[blood]]stream. Studies have shown that higher levels of type-B LDL particles (as opposed to type-A LDL particles) are associated with health problems, including [[cardiovascular disease]].
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| Although the nickname is overly simplistic and thus misleading, LDL molecules are often informally called ''bad cholesterol'' because they can transport their content of many fat molecules into artery walls, attract [[macrophage]]s, and thus drive [[atherosclerosis]]. In contrast, [[high-density lipoprotein|HDL]] molecules are frequently referred to as ''good cholesterol'' or ''healthy cholesterol'', because they can remove fat molecules from [[macrophages]] in the wall of [[artery|arteries]].<ref>[http://www.americanheart.org/presenter.jhtml?identifier=180 LDL and HDL Cholesterol: What's Bad and What's Good?]</ref>
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| ==Testing==
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| [[Blood tests]] typically report LDL-C, the amount of cholesterol contained in LDL. In clinical context, mathematically calculated estimates of LDL-C are commonly used to estimate how much low density lipoproteins are driving progression of [[atherosclerosis]].
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| 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 [[Vertical auto profile|couple of laboratories]] in the United States. In 2008, the [[American Diabetes Association|ADA]] and [[American College of Cardiology|ACC]] recognized direct LDL particle measurement by [[Nuclear magnetic resonance|NMR]] as superior for assessing individual risk of cardiovascular events.<ref>John D. Brunzell, MD, FACP, Michael Davidson, MD, FACC, Curt D. Furberg, MD, PhD, Ronald B. Goldberg, MD, Barbara V. Howard, PhD, James H. Stein, MD, FACC, FACP and Joseph L. Witztum, MD Lipoprotein Management in Patients With Cardiometabolic Risk, J Am Coll Cardiol, 2008; 51:1512-1524. [http://content.onlinejacc.org/cgi/content/full/j.jacc.2008.02.034#BIB25]</ref>
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| ==Biochemistry==
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| ===Structure===
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| Each native LDL particle enables emulsification, i.e surrounding/packaging all fatty acids being carried, enabling these fats to move around the body within the water outside cells. Each particle contains a single [[apolipoprotein]] B-100 molecule ([[apolipoprotein B-100|Apo B-100]], a protein that has 4536 [[amino acid]] residues and a mass of 514 [[kDa]]), along with 80 to 100 additional ancillary proteins. Each LDL has a highly hydrophobic core consisting of polyunsaturated fatty acid known as ''[[Linoleic acid|linoleate]]'' and hundreds to thousands (about 1500 commonly cited as an average) esterified and non-esterified cholesterol molecules. This core also carries varying numbers of triglycerides and other fats and is surrounded by a shell of phospholipids and unesterified cholesterol, as well as the single copy of Apo B-100. LDL particles are approximately 22 nm (0.00000087 in.) in diameter and have a mass of about 3 million [[atomic mass unit|daltons]]. Since LDL particles contain a variable and changing number of fatty acid molecules, there is a distribution of LDL particle mass and size.<ref>{{Cite journal|author=Segrest JP, Jones MK, De Loof H, Dashti N |title=Structure of apolipoprotein B-100 in low density lipoproteins |journal=Journal of Lipid Research |volume=42 |issue=9 |pages=1346–67 |date=September 2001 |pmid=11518754 |url=http://www.jlr.org/cgi/pmidlookup?view=long&pmid=11518754}}</ref> Determining the structure of LDL has been a tough task because of its heterogeneous structure. The structure of LDL at human body temperature in native condition, with a resolution of about 16 Angstroms using cryo-electron microscopy, has been recently described.<ref>{{Cite journal|author=Kumar V, Butcher SJ, Katrina O,Engelhardt P,Heikkonen J, Kaski K, Ala-Korpela M, Kovanen PT. |title=Three-Dimensional cryoEM Reconstruction of Native LDL Particles to 16Å Resolution at Physiological Body Temperature |journal=PLoS ONE |date=May 2011|pmid=21573056 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018841 |doi=10.1371/journal.pone.0018841 |pmc=3090388 |volume=6 |issue=5 |pages=e18841}}</ref>
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| ===LDL subtype patterns===
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| 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 thought to be 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). According to one study, sizes 19.0–20.5 nm were designated as pattern B and LDL sizes 20.6–22 nm were designated as pattern A.<ref>http://onlinelibrary.wiley.com/doi/10.1002/clc.4960280510/pdf</ref>
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| Some in the medical community have suggested the correspondence between Pattern B and CHD is 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 is used more often.<ref>http://www.msnbc.msn.com/id/35058896/ns/health-heart_health/t/bad-cholesterol-its-not-what-you-think/#.T4Gkub_Owrg{{dead link|date=September 2013}}</ref>
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| 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.<ref name="pmid12417832">{{Cite journal|author=Superko HR, Nejedly M, Garrett B |title=Small LDL and its clinical importance as a new CAD risk factor: a female case study |journal=Progress in Cardiovascular Nursing |volume=17 |issue=4 |pages=167–73 |year=2002 |pmid=12417832 |doi=10.1111/j.0889-7204.2002.01453.x}}</ref><ref name="Warnick"/>
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| With continued research, decreasing cost, greater availability and wider acceptance of other ''lipoprotein subclass analysis'' assay methods, including [[NMR spectroscopy]],<ref>{{Cite journal|author=Otvos J |title=Measurement of triglyceride-rich lipoproteins by nuclear magnetic resonance spectroscopy |journal=Clin Cardiol |volume=22 |issue=6 Suppl |pages=II21–7 |date=June 1999 |pmid=10376193 |doi= |url=}}</ref> research studies have continued to show a stronger correlation between human clinically obvious cardiovascular events and quantitatively measured particle concentrations.{{Citation needed|date=September 2011}}
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| ===Transport into the cell===
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| When a cell requires additional cholesterol (beyond its current internal [[HMGCoA]] production pathway), it synthesizes the necessary [[LDL receptors]], and inserts them into the plasma membrane. The LDL receptors diffuse freely until they associate with [[clathrin]]-[[Caveolae|coated pits]]. LDL particles in the bloodstream bind to these extracellular LDL receptors. The clathrin-coated pits then form vesicles that are endocytosed into the cell.
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| After the clathrin coat is shed, the vesicles deliver the LDL and their receptors to early [[endosomes]], onto late endosomes to lysosomes. Here the cholesterol esters in the LDL are hydrolysed. The LDL receptors are recycled back to the plasma membrane.
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| ==Medical relevance - Atherosclerosis==
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| {{Refimprove section|date=April 2010}}
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| {{Advert|section|date=October 2013}}
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| Because LDL particles can also transport cholesterol into the [[artery]] wall, retained there by arterial [[proteoglycan]]s and attract [[macrophages]] that engulf the LDL particles and start the formation of [[Atheroma|plaque]]s, increased levels are associated with [[atherosclerosis]]. Over time [[vulnerable plaque]]s rupture, activate blood clotting and produce arterial [[stenosis]], which if severe enough results in [[myocardial infarction|heart attack]], [[cerebrovascular accident|stroke]], and [[peripheral artery occlusive disease|peripheral vascular disease]] symptoms and major debilitating events.
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| Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles.<ref>[http://www.npr.org/templates/story/story.php?storyId=15886898 Not All Calories Are Created Equal, Author Says]. Talk of the Nation discussion of the book ''[[Good Calories, Bad Calories]]'', by Gary Taubes. National Public Radio, 2 November 2007.</ref> The healthiest pattern A, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern B; high concentrations of small LDL particles (even though potentially carrying the same total cholesterol content as a low concentration of large particles) correlates with much faster growth of [[atheroma]], progression of [[atherosclerosis]] and earlier and more severe cardiovascular disease events and death. This video [http://www.youtube.com/watch?v=F0Y5hss1tZQ], examining autopsy specimens from an actual heart attack resulting in sudden death, shows the seqence. These videos, [http://www.youtube.com/watch?v=XLLBlBiboJI&NR=1] and [http://www.youtube.com/watch?v=w8wXdtoW-HQ&feature=related], illustrate the sequence of events and why, though the underlying process develops over decades, the symptoms are often of sudden onset.
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| LDL particles are formed as [[VLDL]] lipoproteins lose triglyceride through the action of [[lipoprotein lipase]] (LPL) and they become smaller and denser (i.e. fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters [http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/lipoprot.htm].
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| A hereditary form of high LDL is [[familial hypercholesterolemia]] (FH). Increased LDL is termed [[hyperlipoproteinemia type II]] (after the dated [[Fredrickson classification]]).
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| LDL particles pose a risk for [[cardiovascular disease]] when they invade the [[endothelium]] and become [[oxidize]]d, 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 [http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/lipoprot.htm] and [[free radicals]] in the endothelium.
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| ===Role in the innate immune system===
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| [[LDL]] lipoproteins interfere with the [[quorum sensing]] system that upregulates genes required for invasive [[Staphylococcus aureus]] infection. The mechanism of antagonism entails binding [[Apolipoprotein B]], to a S. aureus [[autoinducer]] pheromone, preventing signaling through its receptor. Mice deficient in apolipoprotein B are more susceptible to invasive bacterial infection.<ref name="Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection">{{Cite journal|author=Peterson MM, Mack JL, Hall PR, ''et al.'' |title=Apolipoprotein B Is an innate barrier against invasive Staphylococcus aureus infection |journal=Cell Host & Microbe |volume=4 |issue=6 |pages=555–66 |date=December 2008 |pmid=19064256 |doi=10.1016/j.chom.2008.10.001 |pmc=2639768}}</ref>
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| ===Lowering LDL===
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| {| class="wikitable" style="float:right; width:40em; border:solid 1px #999999; margin:0 0 1em 1em;"
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| ! colspan="5" style="background-color: #CCEEEE;" | Markers indicating a need for LDL Reduction
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| ! If the patient's cardiac risk is...
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| ! then the patient should consider LDL reduction if the count in mg/dL is over...
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| ! and LDL reduction is indicated if the count in mg/dL is over...
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| |-
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| | High, meaning a 20% or greater risk of heart attack within 10 years, or an extreme risk factor
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| | 70<ref name="BBDstatins">{{Citation |author1 =Consumer Reports|author1-link =Consumer Reports |author2 = Drug Effectiveness Review Project |author2-link =Drug Effectiveness Review Project |date=March 2013 |title=Evaluating statin drugs to treat High Cholesterol and Heart Disease: Comparing Effectiveness, Safety, and Price |publisher = Consumer Reports |work = Best Buy Drugs |page = 9 |url = http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/StatinsUpdate-FINAL.pdf |accessdate = 27 March 2013}}, which cites
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| *{{cite web |url= http://www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm |title=NHLBI, High Blood Cholesterol: What You Need to Know |author1=United States Department of Health and Human Services |authorlink1=United States Department of Health and Human Services |author2=National Heart, Lung, and Blood Institute |authorlink2=National Heart, Lung, and Blood Institute |author3=National Institutes of Health |authorlink3=National Institutes of Health |work=nhlbi.nih.gov |date=June 2005 |accessdate=27 March 2013}}</ref>
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| | 100<ref name="BBDstatins"/>
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| |-
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| | moderately high, meaning a 10-20% risk of heart attack within 10 years and more than 2 heart attack risk factors
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| | 100<ref name="BBDstatins"/>
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| | 130<ref name="BBDstatins"/>
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| |-
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| | moderate, meaning a 10% risk of heart attack within 10 years and more than 2 heart attack risk factors
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| | 130<ref name="BBDstatins"/>
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| | 160<ref name="BBDstatins"/>
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| |-
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| | low, meaning less than 10% risk of heart attack within 10 years and 1 or 0 heart attack risk factors
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| | 160<ref name="BBDstatins"/>
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| | 190<ref name="BBDstatins"/>
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| |-
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| |}
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| 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 and performs the first of 37 steps within the cholesterol production pathway, and present in every animal cell.
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| Also keep in mind that LDL particles carry many fat molecules; cholesterol, triglycerides, phospholipids and others. Thus even if the hundreds to thousands of cholesterol molecules within an average LDL particle were measured, this does not reflect the other fat molecules or even the number of LDL particles.
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| ====Pharmaceutical====
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| *[[Statin]]s reduce high levels of LDL particles by inhibiting 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 receptor]]s is increased, resulting in an increased clearance of LDL particles from the blood.
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| *[[Ezetimibe]] reduces intestinal absorption of cholesterol, thus can reduce LDL particle concentrations when combined with statins.<ref>[http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079524.htm]</ref>
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| *PCSK9 inhibitors, in phase 3 clinical trials, by several companies, appear to be far more effective for LDL reduction than the statins, even statins at high dose.
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| *[[Niacin]] (B<sub>3</sub>), lowers LDL by selectively inhibiting hepatic diacyglycerol acyltransferase 2, reducing [[triglyceride]] synthesis and VLDL secretion through a receptor HM74<ref>{{Cite journal|author=Meyers CD, Kamanna VS, Kashyap ML |title=Niacin therapy in atherosclerosis |journal=Current Opinion in Lipidology |volume=15 |issue=6 |pages=659–65 |date=December 2004 |pmid=15529025 |doi=10.1097/00041433-200412000-00006}}</ref> and HM74A or GPR109A.<ref name=pmid17238156>{{Cite journal|author=Soudijn W, van Wijngaarden I, Ijzerman AP |title=Nicotinic acid receptor subtypes and their ligands |journal=Medicinal Research Reviews |volume=27 |issue=3 |pages=417–33 |date=May 2007 |pmid=17238156 |doi=10.1002/med.20102}}</ref>
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| * Several CETP inhibitors have been researched to improve HDL concentrations, but so far, despite dramatically increasing HDL-C, have not had a consistent track record in reducing atherosclerosis disease events. Some have increased mortality rates compared with placebo.
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| *[[Clofibrate]] is effective at lowering cholesterol levels, but has been associated with significantly increased cancer and stroke mortality, despite lowered cholesterol levels.<ref>{{Cite journal|author= |title=WHO cooperative trial on primary prevention of ischemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Report of the Committee of Principal Investigators |journal=Lancet |volume=2 |issue=8403 |pages=600–4 |date=September 1984 |pmid=6147641}}</ref> Other, more recently developed and tested fibrates, e.g. fenofibric acid [http://www.rxabbott.com/pdf/trilipix_pi.pdf] 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.
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| *Some [[Tocotrienol]]s, especially delta- and gamma-tocotrienols, are being promoted as statin alternative non-prescription agents to treat high cholesterol, having been shown in vitro to have an effect. In particular, gamma-tocotrienol appears to be another HMG-CoA reductase inhibitor, and can reduce cholesterol production.<ref>{{Cite journal|last= Song |first= B.L. |coauthors= DeBose-Boyd, R.A.|year=2006 |title=Insig-Dependent Ubiquitination and Degradation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Stimulated by Delta- and Gamma-Tocotrienols |journal=J. Biol. Chem. |volume=281|issue=35 |pages=25054–25601 |doi= 10.1074/jbc.M605575200 |pmid= 16831864}}</ref> 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 benefits and complications of such agents compare with statins—molecular tools that have been analyzed in large numbers of human research and clinical trials since the mid-1970s.
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| *[[Phytosterols]] are widely recognized as having a proven LDL cholesterol lowering efficacy.<ref>{{cite web | author = European Food Safety Authority, Journal | url = http://www.efsa.europa.eu/en/efsajournal/pub/1813.htm | title = Scientific opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations | year = 2010}}</ref> Current supplemental guidelines recommend doses of phytosterols in the 1.6-3.0 grams per day range (Health Canada, EFSA, ATP III,FDA) with a recent meta-analysis demonstrating an 8.8% reduction in LDL-cholesterol at a mean dose of 2.15 gram per day.<ref>{{cite journal|last=Demonty|first=I|coauthors=Ras, RT, van der Knaap, HC, Duchateau, GS, Meijer, L, Zock, PL, Geleijnse, JM, Trautwein, EA|title=Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.|journal=The Journal of nutrition|date=2009 0Feb|volume=139|issue=2|pages=271–84|pmid=19091798|doi=10.3945/jn.108.095125}}</ref> However, plant sterols and stanols, if absorbed (intestinal cells generally block), greatly accelerate progression of atherosclerosis more than cholesterol delivered into the arterial walls by lipoprotein particles{{citation needed|date=April 2013}}.
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| *[[Insulin]] induces HMG-CoA reductase activity, whereas [[glucagon]] diminishes HMG-CoA reductase activity.<ref>[http://themedicalbiochemistrypage.org/cholesterol.html#regulation Regulation of Cholesterol Synthesis ]</ref> While glucagon production is stimulated by dietary protein ingestion, insulin production is stimulated by dietary carbohydrate.{{citation needed|date=April 2013}} 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.
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| *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).<ref name=pmid17238156/>
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| *Lowering the blood lipid concentration of [[triglycerides]] helps lower the concentration of small LDL particles, because fat rich VLDL particles convert in the bloodstream into Small LDL particles.{{Vague|reason=Readers may not know triglycerides are part of VLDL, let alone how reducing former necessarily reduces latter|date=December 2009}}
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| ====Dietary====
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| *The most effective approach has been minimizing fat stores located inside the [[abdominal cavity]] (visceral body fat) in addition to minimizing total body fat.{{Citation needed|date=February 2011}} [[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]].
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| ===Importance of antioxidants===
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| Because LDL particles appear harmless until they are within the blood vessel walls and oxidized by free radicals,<ref>[http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=404450 Inhibition of in vitro human LDL oxidation by phenolic antioxidants from grapes and wines. Teissedre, P.L. : Frankel, E.N. : Waterhouse, A.L. : Peleg, H. : German, J.B.] J-sci-food-agric. Sussex : John Wiley : & : Sons Limited. Jan 1996. v. 70 (1) p. 55-61.</ref> it is postulated that ingesting [[antioxidants]] and minimizing free radical exposure may reduce LDL's contribution to atherosclerosis, though results are not conclusive.<ref>{{Cite journal|author=Esterbauer H, Puhl H, Dieber-Rotheneder M, Waeg G, Rabl H |title=Effect of antioxidants on oxidative modification of LDL |journal=Annals of Medicine |volume=23 |issue=5 |pages=573–81 |year=1991 |pmid=1756027 |doi=10.3109/07853899109150520}}</ref><ref name="PMID 15383655">{{cite journal |author=Stocker R, Keaney JF Jr |title=Role of oxidative modifications in atherosclerosis |journal=Physiol Rev |volume=84 |pages=1381–478 |year=2004 |doi=10.1152/physrev.00047.2003 |pmid=15383655 |issue=4}}</ref> Studies have reported the benefits of green tea in helping to reduce LDL; some studies have focused on the [[antioxidant]] qualities of the unfermented green tea leaves,<ref name=JAmCollNutr200804>{{cite journal|last=Tinahones|first=FJ|coauthors=Rubio MA, Garrido-Sánchez L, Ruiz C, Gordillo E, Cabrerizo L, Cardona F|title=Green tea reduces LDL oxidability and improves vascular function|journal=J Am Coll Nutr|date=April 2008|volume=27(2)|pages=209–13|accessdate=28 February 2012|pmid=18689551|issue=2}}</ref> others looked at green-tea compounds called catechins which are thought to decrease cholesterol absorption in the gut.<ref name=reuters20120228>{{cite news|last=Norton|first=Amy|title=Green tea may trim "bad" cholesterol: study|url=http://www.reuters.com/article/2011/11/17/us-tea-idUSTRE7AG0BD20111117|publisher=Reuters Health|accessdate=28 February 2012|date=17 November 2011}}</ref>
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| ==Estimation of LDL particles via cholesterol content==
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| Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available.
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| The lipid profile does not measure LDL particles directly but instead estimates them using the Friedewald equation<ref name="Warnick">{{Cite journal|author=Warnick GR, Knopp RH, Fitzpatrick V, Branson L |title=Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints |journal=Clinical Chemistry |volume=36 |issue=1 |pages=15–9 |date=January 1990 |pmid=2297909 |url=http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=2297909}}</ref><ref name="pmid4337382">{{Cite journal|author=Friedewald WT, Levy RI, Fredrickson DS |title=Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge |journal=Clinical Chemistry |volume=18 |issue=6 |pages=499–502 |date=June 1972 |pmid=4337382 |url=http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=4337382}}</ref>
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| by subtracting the amount of cholesterol associated with other particles, such as [[High density lipoprotein|HDL]] and [[Very low-density lipoprotein|VLDL]], assuming a prolonged fasting state, etc.:
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| :<math>L \approx C - H - kT</math>
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| :where ''H'' is HDL cholesterol, ''L'' is LDL cholesterol, ''C'' is total cholesterol, ''T'' are triglycerides, and k is 0.20 if the quantities are measured in mg/dl and 0.45 if in mmol/l.
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| There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52 mmol/L (400 mg/dL). Even at triglyceride levels 2.5 to 4.5 mmol/L, this formula is considered inaccurate.<ref name="Sniderman">{{Cite journal|author=Sniderman AD, Blank D, Zakarian R, Bergeron J, Frohlich J |title=Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula |journal=Clinical Biochemistry |volume=36 |issue=7 |pages=499–504 |date=October 2003 |pmid=14563441 |doi=10.1016/S0009-9120(03)00117-6}}</ref> If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dl, may be used
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| :<math>L = C - H - 0.16T</math>
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| This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer.
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| However, the concentration of LDL particles, and to a lesser extent their size, has a slightly stronger correlation with individual clinical outcome than the amount of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct. There is increasing evidence and recognition of the value of more targeted and accurate measurements of LDL particles. Specifically, LDL particle number (concentration), and to a lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles [http://www.liposcience.com/userfiles/content/files/weightofevidence.pdf]. It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. If LDL particle concentration is used to predict cardiovascular events, many other correlates of these clinical outcomes, such as [[diabetes mellitus]], obesity and smoking, loose most of their predictive accuracy.
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| ===Normal ranges===
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| In the USA, the [[American Heart Association]], [[National Institutes of Health|NIH]], and [[National Cholesterol Education Program|NCEP]] provide a set of guidelines for fasting LDL-Cholesterol levels, estimated or measured, and risk for [[Coronary heart disease|heart disease]]. As of about 2005, these guidelines were:<ref>
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| {{Cite web
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| | url=http://www.americanheart.org/presenter.jhtml?identifier=4500
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| | title=Cholesterol Levels
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| | publisher=American Heart Association
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| | accessdate=2009-11-14
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| }}</ref><ref>
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| {{Cite web
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| | url=http://www.americanheart.org/downloadable/heart/119618151049911%20CholLevels%209_07.pdf
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| | title=What Do My Cholesterol Levels Mean?
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| | publisher=American Heart Association
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| | format=PDF
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| | date=September 2007
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| | accessdate=2009-11-14
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| }}</ref><ref>
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| {{Cite web
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| |url=http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf
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| |title=Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Executive Summary
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| | date=May 2001
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| | work=National Heart, Lung, and Blood Institute (NHLBI)
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| | publisher=National Institutes of Health
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| }}</ref>
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| {| class="wikitable"
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| ! Level [[kilogram|mg]]/[[litre|dL]]
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| ! Level [[mole (unit)|mmol]]/L
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| ! Interpretation
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| |-
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| | 25 to <50
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| | <1.3
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| | Optimal LDL cholesterol, levels in healthy young children before onset of atherosclerotic plaque in heart artery walls
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| |-
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| | <70
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| | <1.8
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| | Optimal LDL cholesterol, corresponding to lower rates of progression, promoted as a target option for those known to clearly have advanced symptomatic cardiovascular disease
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| |-
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| | <100
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| | <2.6
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| | Optimal LDL cholesterol, corresponding to lower, but not zero, rates for symptomatic cardiovascular disease events
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| |-
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| | 100 to 129
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| | 2.6 to 3.3
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| | Near optimal LDL level, corresponding to higher rates for developing symptomatic cardiovascular disease events
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| |-
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| | 130 to 159
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| | 3.3 to 4.1
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| | Borderline high LDL level, corresponding to even higher rates for developing symptomatic cardiovascular disease events
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| |-
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| | 160 to 199
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| | 4.1 to 4.9
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| | High LDL level, corresponding to much higher rates for developing symptomatic cardiovascular disease events
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| |-
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| | >200
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| | >4.9
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| | Very high LDL level, corresponding to highest increased rates of symptomatic cardiovascular disease events
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| |}
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| Over time, with more clinical research, these recommended levels keep being reduced because LDL reduction, including to abnormally low levels, was the most effective strategy for reducing cardiovascular death rates in one large [[double blind]], randomized clinical trial of men with hypercholesterolemia;<ref name="pmid7566020 ">{{Cite journal|author=Shepherd J, Cobbe SM, Ford I, ''et al.'' |title=Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group |journal=The New England Journal of Medicine |volume=333 |issue=20 |pages=1301–7 |date=November 1995 |pmid=7566020 |doi=10.1056/NEJM199511163332001}}</ref> far more effective than coronary angioplasty/stenting or bypass surgery <ref>{{Cite journal|author=William E. Boden, M.D., ''et al.'' |title=Optimal Medical Therapy with or without PCI for Stable Coronary Disease |journal=The New England Journal of Medicine |volume=356 |pages=1503–1516|date=April 2007 |DOI= 10.1056/NEJMoa070829 }}</ref>
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| For instance, for people with known atherosclerosis diseases, the 2004 updated [[American Heart Association]], NIH and NCEP recommendations are for LDL levels to be lowered to less than 70 mg/dL, unspecified how much lower. This low level of less than 70 mg/dL was recommended for primary prevention of 'very-high risk patients' and in secondary prevention as a 'reasonable further reduction'. Lack of evidence for such a recommendation is discussed in an article in the [[Annals of internal medicine]].<ref>[http://www.annals.org/content/145/7/520.full Narrative Review: Lack of Evidence for Recommended Low-Density Lipoprotein Treatment Targets: A Solvable Problem]</ref> It should also be noted that statin drugs involved in such clinical trials have [[Pleiotropy (drugs)|numerous physiological effects]] beyond simply the reduction of LDL levels.
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| It has been estimated from the results of multiple human pharmacologic LDL lowering trials{{Citation needed|date=October 2007}} that LDL should be lowered to about 50 to reduce cardiovascular event rates to near zero. For reference, from longitudinal population studies following progression of atherosclerosis-related behaviors from early childhood into adulthood,{{Citation needed|date=October 2007}} it has been discovered that the usual LDL in childhood, before the development of [[fatty streaks]], is about 35 mg/dL. However, all the above values refer to chemical measures of lipid/cholesterol concentration within LDL, not measured Low Density Lipoprotein concentrations, the accurate approach.
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| The feasibility of these figures has been questioned by sceptics, claiming that many members of the AHA and NIH are heavily associated with pharmaceutical companies giving them bias towards lowering cholesterol levels and such guidelines giving rise to increased use of cholesterol lowering medicine such as statins.{{Citation needed|date=October 2011}}
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| A study was conducted measuring the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits in the US from 1995 to 2004. It was found that although LDL cholesterol reporting and control for diabetes and coronary heart disease visits improved continuously between 1995 and 2004, neither the 1998 ADA guidelines nor the 2001 ATP III guidelines increased [http://www.cholesterolverlagen.nu/bloedcholesterol-verlagen/ldl-bloedcholesterol-verlagen.php LDL cholesterol] control for diabetes relative to coronary heart disease.<ref name=wang>{{cite journal|last=Wang|first=Y Richard|coauthors=G Caleb Alexander and David O Meltzer|title=Lack of Effect of Guideline Changes on LDL Cholesterol Reporting and Control for Diabetes Visits in the U.S., 1995–2004|journal=Diabetes Care|date=December 2005|volume=28|issue=12|pages=2942–2944|pmid=16306559|url=http://www.ncbi.nlm.nih.gov/pubmed?term=16306559|accessdate=2011-11-11}}</ref>
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| Moreover, there are publications<ref>[http://www.ncbi.nlm.nih.gov/pubmed/18000291 Low serum LDL cholesterol levels and the risk of fever, sepsis, and malignancy.]</ref> regarding the risks of low-LDL cholesterol too.
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| ==Direct measurement of LDL particle concentrations==
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| There are several competing methods for measurement of lipoprotein particle size although the evidence in favor of their superiority to existing methods is weak, even by the statements of proponents.<ref>{{cite journal|pmid=20531184 | doi=10.1097/MOL.0b013e32833b7756 | volume=21 | issue=4 | title=Lipoprotein subfractions and cardiovascular disease risk |date=August 2010 | author=Krauss RM | journal=Current Opinion in Lipidology | pages=305–11}}</ref> Direct LDL particle measurement by [[NMR]] was mentioned by the [[American Diabetes Association|ADA]] and [[American College of Cardiology|ACC]], in a 28 March 2008 joint consensus statement,<ref>[http://content.onlinejacc.org/cgi/content/full/j.jacc.2008.02.034#BIB25]</ref> as having advantages for predicting individual risk of atherosclerosis disease events, but the statement noted that the test is not widely available and is more expensive (about $98.00 US without insurance coverage) than existing tests. Furthermore the authors also said it is "...unclear whether LDL particle size measurements add value to measurement of LDL particle concentration." Since the later 1990s, because of the development of NMR measurements, it has been possible to clinically measure lipoprotein particles at lower cost [under $100 US (including shipping) versus the previous costs of >$400 to >$5,000] and high accuracy. There are also other (less expensive) homogeneous assays for LDL, however most only estimate LDL.
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| Using NMR, as pioneered by researcher [[Jim Otvos]] and the North Carolina State University academic research spinoff company [http://www.liposcience.com LipoScience], the total LDL particle concentrations, in nmol/L plasma, are typically subdivided by percentiles referenced to the 5,382 men and women, not on any lipid medications, who participated in the MESA trial.<ref>[http://www.mesa-nhlbi.org/]</ref>
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| ===Optimal ranges===
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| The LDL particle concentrations are typically categorized by percentiles, <20%, 20–50%, 50th–80th%, 80th–95% and >95% groups of 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.
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| {| class="wikitable"
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| ! MESA Percentile
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| ! LDL particles [[mole (unit)|nmol]]/L
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| ! Interpretation
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| |-
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| | 0–20%
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| | <1,000
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| | Those with lowest rate of cardiovascular disease events & low (optimal) LDL particle concentration
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| |-
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| | 20–50%
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| | 1,000–1,299
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| | Those with moderate rate of cardiovascular disease events & moderate LDL particle concentration
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| |-
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| | 50–80%
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| | 1,300–1,599
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| | Those with Borderline-High rate of cardiovascular disease events & higher LDL particle concentration
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| |-
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| | 89–95%
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| | 1,600–2,000
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| | Those with High rate of cardiovascular disease events and even higher LDL particle concentration
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| |-
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| | >95%
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| | >2,000
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| | Those with very high rate of cardiovascular disease events and highest LDL particle concentration
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| |}
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| The lowest incidence of atherosclerotic events over time occurs within the <20% group, with increased rates for the higher groups. Multiple other measures, including particle sizes, small LDL particle concentrations, total and large [[High-density lipoprotein|HDL]] particle concentrations, along with estimations of [[insulin resistance]] pattern and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are also routinely provided.
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| ==See also==
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| <div style="-moz-column-count:3; column-count:3;">
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| * [[Catechin]]
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| * [[Cholesterol]]
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| * [[Lysosomal acid lipase deficiency]]
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| * [[Cholesteryl ester storage disease]]
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| * [[Coenzyme Q10]]
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| * [[Flavonoid]]
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| * [[Glutathione]]
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| * [[Health effects of tea]]
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| * [[High density lipoprotein]]
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| * [[LDL receptor]]
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| * [[Lipid profile]]
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| * [[Lipoprotein(a)]]
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| * [[Lipoprotein-X]]
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| * [[Melatonin]]
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| * [[Polyphenol antioxidant]]
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| * [[Saturated fat]]
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| * [[Stanol ester]]
| |
| * [[Sterol ester]]
| |
| * [[Triglyceride]]
| |
| * [[Vitamin A]]
| |
| * [[Vitamin C]]
| |
| * [[Vitamin E]]
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| </div>
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| | |
| ==Footnotes==
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| {{Reflist}}
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| ==External links==
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| *[http://www.youtube.com/watch?v=XPguYN7dcbE Fat (LDL) Degradation]: PMAP [[The Proteolysis Map]]-animation
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| *[http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm Adult Treatment Panel III Full Report]
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| *[http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm ATP III Update 2004]
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| * LDL Cholesterol at [http://labtestsonline.org/understanding/analytes/ldl/tab/test Lab Tests Online]
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| *{{Cite journal|author=O'Keefe JH, Cordain L, Harris WH, Moe RM, Vogel R |title=Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal |journal=Journal of the American College of Cardiology |volume=43 |issue=11 |pages=2142–6 |date=June 2004 |pmid=15172426 |doi=10.1016/j.jacc.2004.03.046}}
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| {{Lipoproteins}}
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| {{Vascular diseases}}
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| {{Use dmy dates|date=September 2010}}
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| {{DEFAULTSORT:Low-Density Lipoprotein}}
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| [[Category:Cardiology]]
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| [[Category:Lipid disorders]]
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| [[Category:Lipoproteins]]
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