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| {{Infobox disease
| | Alyson Meagher is the title her mothers and fathers gave her but she doesn't like when individuals use her full name. To climb is some thing I truly enjoy doing. Her family members life in Ohio. Credit authorising is how he tends to make cash.<br><br>Also visit my web site ... clairvoyance ([http://www.the-gay-tube.com/users/DPalladin the-gay-tube.com]) |
| | Name = Hypercholesterolemia
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| | Image = Cholesterol.svg
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| | Caption = Formula structure of [[cholesterol]]
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| | ICD10 = {{ICD10|E|78|0|e|70}}
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| | ICD9 = {{ICD9|272.0}}
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| | ICDO =
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| | OMIM =
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| | DiseasesDB = 6226
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| | MedlinePlus = 000403
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| | eMedicineSubj = med
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| | eMedicineTopic = 1073
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| | MeshID = D006937
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| }}
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| '''Hypercholesterolemia''' ([[American and British English spelling differences#Simplification of ae and oe|also spelled]] '''hypercholesterolaemia''') is the presence of high levels of [[cholesterol]] in the blood.<ref name=Durrington>{{cite journal|last=Durrington|first=P|title=Dyslipidaemia|journal=[[The Lancet]]|volume=362|issue=9385|pages=717–31|date=August 2003 |pmid=12957096|doi=10.1016/S0140-6736(03)14234-1|url=}}</ref> It is a form of "[[hyperlipidemia]]" (elevated levels of [[lipid]]s in the blood) and "hyperlipoproteinemia" (elevated levels of [[lipoprotein]]s in the blood).<ref name=Durrington/>
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| Cholesterol is a [[sterol]]; see the diagrammatic structure at the right. It is one of three major classes of [[lipid]]s which all animal cells utilize to construct their membranes and is thus manufactured by all animal cells. Plant cells do not manufacture cholesterol. It is also the precursor of the [[steroid hormone]]s, [[bile acid]]s and [[vitamin D]].
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| Since cholesterol is insoluble in water, it is transported in the blood plasma within protein particles ([[lipoproteins]]). Lipoproteins are classified by their density: [[very low density lipoprotein]] (VLDL), [[intermediate density lipoprotein]] (IDL), [[low density lipoprotein]] (LDL) and [[high density lipoprotein]] (HDL).<ref>{{cite journal |author=Biggerstaff KD, Wooten JS |title=Understanding lipoproteins as transporters of cholesterol and other lipids |journal=Adv Physiol Educ |volume=28 |issue=1–4 |pages=105–6 |date=December 2004 |pmid=15319192 |doi=10.1152/advan.00048.2003 |url=}}</ref> All the lipoproteins carry cholesterol, but elevated levels of the lipoproteins other than HDL (termed non-HDL cholesterol), particularly LDL-cholesterol are associated with an increased risk of [[atherosclerosis]] and [[coronary heart disease]].<ref>{{cite journal |author=Carmena R, Duriez P, Fruchart JC |title=Atherogenic lipoprotein particles in atherosclerosis |journal=Circulation |volume=109 |issue=23 Suppl 1 |pages=III2–7 |date=June 2004 |pmid=15198959 |doi=10.1161/01.CIR.0000131511.50734.44 |url=}}</ref> In contrast higher levels of HDL cholesterol are protective.<ref>{{cite journal |author=Kontush A, Chapman MJ |title=Antiatherogenic small, dense HDL--guardian angel of the arterial wall? |journal=Nat Clin Pract Cardiovasc Med |volume=3 |issue=3 |pages=144–53 |date=March 2006 |pmid=16505860 |doi=10.1038/ncpcardio0500 |url=}}</ref> Elevated levels of non-HDL cholesterol and LDL in the blood may be a consequence of [[diet (nutrition)|diet]], [[obesity]], inherited (genetic) diseases (such as [[LDL receptor]] mutations in [[familial hypercholesterolemia]]), or the presence of other diseases such as [[diabetes mellitus|diabetes]] and [[hypothyroidism|an underactive thyroid]].<ref name=Durrington/>
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| Reducing dietary fat is recommended to reduce total blood cholesterol and LDL in adults.<ref name=Hooper>{{cite journal |author=Hooper L, Summerbell CD, Thompson R, ''et al.'' |title=Reduced or modified dietary fat for preventing cardiovascular disease |journal=Cochrane Database Syst Rev |volume=5 |issue= |pages=CD002137 |year=2012 |pmid=22592684 |doi=10.1002/14651858.CD002137.pub3 |editor1-last=Hooper |editor1-first=Lee}}</ref> In people with very high cholesterol (e.g. familial hypercholesterolemia), diet is often insufficient to achieve the desired lowering of LDL and lipid lowering [[Pharmaceutical drug|medications]] which reduce cholesterol production or absorption are usually required.<ref name=Ito2011>{{cite journal |author=Ito MK, McGowan MP, Moriarty PM |title=Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia |journal=J Clin Lipidol |volume=5 |issue=3 Suppl |pages=S38–45 |date=June 2011 |pmid=21600528 |doi=10.1016/j.jacl.2011.04.001 |url=}}</ref> If necessary, other treatments such as LDL [[apheresis]] or even surgery (for particularly severe subtypes of familial hypercholesterolemia) are performed.<ref name = Ito2011/>
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| ==Signs and symptoms==
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| [[File:Xanthelasma palpebrarum.jpg|thumb|[[Xanthelasma|Xanthelasma palpebrarum]], yellowish patches consisting of cholesterol deposits above the eyelids. These are more common in people with [[familial hypercholesterolemia]].]]
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| Although hypercholesterolemia itself is [[asymptomatic]], longstanding elevation of serum cholesterol can lead to [[atherosclerosis]].<ref name="BMJ2008">{{cite journal |author=Bhatnagar D, Soran H, Durrington PN |title=Hypercholesterolaemia and its management |journal=BMJ |volume=337 |issue= |pages=a993 |year=2008 |pmid=18719012 |doi= 10.1136/bmj.a993|url=}}</ref> Over a period of decades, chronically elevated serum cholesterol contributes to formation of [[atheroma|atheromatous plaques]] in the arteries. This can lead to progressive [[stenosis]] (narrowing) or even complete [[Vascular occlusion|occlusion]] (blockage) of the involved arteries. Alternatively smaller plaques may rupture and cause a clot to form and obstruct blood flow.<ref>{{cite journal |author=Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R |title=Concept of vulnerable/unstable plaque |journal=Arterioscler. Thromb. Vasc. Biol. |volume=30 |issue=7 |pages=1282–92 |date=July 2010 |pmid=20554950 |doi=10.1161/ATVBAHA.108.179739 |url=}}</ref> A sudden occlusion of a coronary artery results in a [[myocardial infarction]] or heart attack. An occlusion of an artery supplying the brain can cause a [[stroke]]. If the development of the stenosis or occlusion is gradual blood supply to the tissues and organs slowly diminishes until organ function becomes impaired. At this point that tissue [[ischemia]] (restriction in blood supply) may manifest as specific [[symptom]]s. For example, temporary ischemia of the brain (commonly referred to as a [[transient ischemic attack]]) may manifest as temporary loss of vision, [[dizziness]] and impairment of [[equilibrioception|balance]], [[aphasia]] (difficulty speaking), [[paresis]] (weakness) and [[paresthesia]] (numbness or tingling), usually on one side of the body. Insufficient blood supply to the heart may manifest as [[angina pectoris|chest pain]], and ischemia of the eye may manifest as [[amaurosis fugax|transient visual loss in one eye]]. Insufficient blood supply to the legs may manifest as [[claudication|calf pain when walking]], while in the intestines it may present as [[Abdominal angina|abdominal pain after eating a meal]].<ref name=Durrington/><ref name=Grundy1998>{{cite journal |last1=Grundy |first1=SM |last2=Balady |first2=GJ |last3=Criqui|first3=MH |last5=Greenland |first5=P |last6=Hiratzka |first6=LF |last7=Houston-Miller |first7=N |last8=Kris-Etherton |first8=P |last9=Krumholz |first9=HM |title=Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA Task Force on Risk Reduction. American Heart Association |journal=[[Circulation (journal)|Circulation]] |volume=97 |issue=18 |pages=1876–87 |year=1998 |pmid=9603549 |url=http://circ.ahajournals.org/cgi/content/full/97/18/1876 |doi=10.1161/01.CIR.97.18.1876 |last4=Fletcher |first4=G |last10=Larosa |first10=J. |last11=Ockene |first11=I. S. |last12=Pearson |first12=T. A. |last13=Reed |first13=J. |last14=Washington |first14=R. |last15=Smith |first15=S. C. }}</ref>
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| Some types of hypercholesterolemia lead to specific physical findings. For example, familial hypercholesterolemia (Type IIa hyperlipoproteinemia) may be associated with [[xanthelasma|xanthelasma palpebrarum]] (yellowish patches underneath the skin around the eyelids),<ref name=Shields2008>{{cite book |last1=Shields |first1=C |last2=Shields |first2=J |title=Eyelid, conjunctival, and orbital tumors: atlas and textbook |publisher=Lippincott Williams & Wilkins |location=Hagerstown, Maryland |year=2008 |isbn=0-7817-7578-7 }}</ref> [[arcus senilis]] (white or gray discoloration of the peripheral [[cornea]]),<ref name=Zech2008>{{cite journal |title=Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia |author=Zech LA Jr, Hoeg JM |journal=Lipids Health Dis |date=2008-03-10 |volume=7 |page=7 |pmid=18331643 |doi=10.1186/1476-511X-7-7 |pmc=2279133}}</ref> and [[xanthoma]]ta (deposition of yellowish cholesterol-rich material) of the [[tendon]]s, especially of the fingers.<ref name=Andrews2006>{{cite book |last1=James|first1=WD |last2=Berger|first2=TG |title=Andrews' Diseases of the Skin: Clinical Dermatology |publisher=Saunders Elsevier|year=2006|pages=530–2 |isbn=0-7216-2921-0 |url=}}</ref><ref name=Rapini2007>{{cite book |last1=Rapini|first1=RP |last2=Bolognia|first2=JL |last3=Jorizzo|first3=JL |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis, Missouri |year=2007 |pages=1415–6 |isbn=1-4160-2999-0 }}</ref> Type III hyperlipidemia may be associated with xanthomata of the palms, knees and elbows.<ref name=Andrews2006/>
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| ==Causes==
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| Hypercholesterolemia is typically due to a combination of environmental and genetic factors.<ref name="BMJ2008"/> Environmental factors include [[obesity]] and [[dietary]] choices.<ref name=BMJ2008/> Genetic contributions are usually due to the additive effects of multiple genes, though occasionally may be due to a single gene defect such as in the case of [[familial hypercholesterolaemia]].<ref name=BMJ2008/> A number of secondary causes exist including: [[diabetes mellitus type 2]], [[obesity]], [[alcohol]], [[monoclonal gammopathy]], [[dialysis]], [[nephrotic syndrome]], [[obstructive jaundice]], [[hypothyroidism]], [[Cushing’s syndrome]], [[anorexia nervosa]], medications ([[thiazide diuretics]], [[ciclosporin]], [[glucocorticoids]], [[beta blockers]], [[retinoic acid]]).<ref name=BMJ2008/>
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| ===Diet===
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| [[File:Lipemic plasma.jpg|thumb|alt=A color photograph of two bags of thawed fresh frozen plasma. The bag on the left was obtained from a donor with hypercholesterolemia, and contains cloudy yellow fluid, while the bag obtained from a normal donor contains clear yellow fluid.|Two bags of [[fresh frozen plasma]]. The bag on the left was obtained from a [[Blood donation|donor]] with [[Hyperlipidemia]], while the other bag was obtained from a donor with normal [[Blood lipids|serum lipid]] levels.]]
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| Diet has an important effect on blood cholesterol but the size of this effect varies substantially between individuals.<ref>{{cite journal |author=Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines JA |title=Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis |journal=Am. J. Clin. Nutr. |volume=65 |issue=6 |pages=1747–64 |date=June 1997 |pmid=9174470 |doi= |url=}}</ref> Approximately 50% of non-esterified cholesterol is absorbed in the intestine,<ref name = Lichtenstein>{{cite journal |author=Lichtenstein AH |title=Intestinal cholesterol metabolism |journal=Ann. Med. |volume=22 |issue=1 |pages=49–52 |date=February 1990 |pmid=2184845 |doi=10.3109/07853899009147241 |url=}}</ref> but inter-individual variations in the efficiency of uptake, and the effect of other dietary components such as plant sterols and fiber content affect absorption.<ref name = Lichtenstein/> Moreover, when dietary cholesterol intake goes down, production (principally by the liver<ref name = Stryer>{{cite book |author=Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. |title=Biochemistry |publisher=W.H. Freeman |location=San Francisco |year=2007 |pages= |isbn=0-7167-8724-5 |oclc= |doi= |accessdate=}}</ref>) typically increases, though not always with complete compensation, so that reductions in blood cholesterol can be modest. Reductions in fat intake, particularly saturated fats, also reduce blood cholesterol.<ref>{{cite journal |author=Sacks FM, Katan M |title=Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease |journal=Am. J. Med. |volume=113 Suppl 9B |issue= |pages=13S–24S |date=December 2002 |pmid=12566134 |doi= |url=}}</ref> Dietary sucrose and fructose can raise LDL cholesterol levels in the blood.<ref>{{cite journal|last=Schaefer|first=EJ|coauthors=Gleason, JA; Dansinger, ML|title=Dietary fructose and glucose differentially affect lipid and glucose homeostasis|journal=The Journal of nutrition|date=June 2009|volume=139|issue=6|pages=1257S–1262S|pmid=19403705|doi=10.3945/jn.108.098186|pmc=2682989}}</ref> In the United States, the National Lipid Association Expert Panel on Familial Hypercholesterolemia recommends that people with familial hypercholesterolemia restrict intakes of total fat to 25 - 35% of energy intake; that saturated fatty acids should make up less than 7% of energy intake, and that cholesterol intake should be less than 200 mg per day.<ref name =Ito2011/> There is also evidence that inclusion of 2 g per day of plant stanol or sterol esters and 10 to 20 g per day of soluble fiber decrease dietary cholesterol absorption.<ref name =Ito2011/> Dietary changes can typically achieve reductions of 10 to 15% in blood cholesterol.<ref name =Ito2011/>
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| Maintaining a healthy body weight through increased physical activity and appropriate caloric intake is also important. Overweight or obese individuals can lower blood cholesterol by losing weight - on average a kilogram of weight loss can reduce LDL cholesterol by 0.8 mg/dL.<ref name =Ito2011/>
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| ===Genetics===
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| Genetic abnormalities are in some cases completely responsible for hypercholesterolemia, such as in familial hypercholesterolemia where there is one or more [[genetic mutation]]s in the [[autosomal dominant]] [[APOB]] gene, the [[autosomal recessive]] [[LDLRAP1]] gene, autosomal dominant [[familial hypercholesterolemia]] (HCHOLA3) variant of the [[PCSK9]] gene, or the [[LDLR|LDL receptor gene]].<ref name=ghr>{{cite web |url=http://ghr.nlm.nih.gov/condition=hypercholesterolemia |work=Genetics Home Reference |title=Hypercholesterolemia |publisher=U.S. National Institutes of Health |accessdate=5 December 2013 }}</ref>
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| Even when there is no single mutation responsible for hypercholesterolemia, genetic predisposition still plays a major role in combination with sedentary lifestyle, obesity, or an [[atherogenic diet]].<ref name=Citko2010>{{cite web |title=Polygenic Hypercholesterolemia |author=Citkowitz E, Isley WL |year=2010 |work=eMedicine |publisher=[[Medscape]] |url=http://emedicine.medscape.com/article/121424-overview |accessdate=2010-11-04}}</ref>
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| ==Diagnosis==
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| {{See also|High-density lipoprotein#Recommended ranges|Low-density lipoprotein#Normal ranges}}
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| {| class="wikitable" style="float:right; width:40em; border:solid 1px #999999; margin:0 0 1em 1em;"
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| |-
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| ! colspan="4" style="background-color: #CCEEEE;" | Interpretation of Cholesterol levels
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| |-
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| ! cholesterol type
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| ! mg/dL
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| ! mmol/L
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| ! interpretation
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| |-
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| |rowspan="3"| total cholesterol
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| | under 200
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| | under 5.2
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| | desirable<ref name="BBDstatins">{{Cite journal |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 |postscript =<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}, 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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| |-
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| | 200-239
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| | 5.2-6.2
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| | borderline<ref name="BBDstatins"/>
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| |-
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| | over 240
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| | over 6.2
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| | high<ref name="BBDstatins"/>
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| |-
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| |rowspan="5"|[[LDL cholesterol]]
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| | under 100
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| | under 2.6
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| | most desirable<ref name="BBDstatins"/>
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| |-
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| | 100-129
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| | 2.6-3.3
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| | good<ref name="BBDstatins"/>
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| |-
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| | 130-159
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| | 3.4-4.1
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| | borderline high<ref name="BBDstatins"/>
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| |-
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| | 160-189
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| | 4.1-4.9
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| | high and undesirable<ref name="BBDstatins"/>
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| |-
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| | over 190
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| | over 4.9
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| | very high<ref name="BBDstatins"/>
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| |-
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| | rowspan="5"|[[HDL cholesterol]]
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| | under 40
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| | under 1.0
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| | undesirable; risk increased<ref name="BBDstatins"/>
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| |-
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| | 41-59
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| | 1.0-1.5
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| | okay, but not optimal<ref name="BBDstatins"/>
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| |-
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| | over 60
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| | over 1.55
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| | good; risk lowered<ref name="BBDstatins"/>
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| |-
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| |}
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| | |
| {| class="wikitable" style="float:right; width:40em; border:solid 1px #999999; margin:0 0 1em 1em;"
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| |-
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| ! colspan="4" style="background-color: #CCEEEE;" | Indications to lower LDL cholesterol
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| |-
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| ! Persons whose coronary risk is...
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| ! because they have...
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| ! should consider lowering LDL if the level is over...
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| ! and LDL reduction is indicated if the level is over...
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| |-
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| | high
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| | greater than 20% risk of heart attack in 10 years, or an extreme risk factor such as coronary heart disease, diabetes, peripheral-artery disease, carotid-artery disease, or aortic aneurysm
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| | 70 mg/dL, 3.88 mmol/dL especially if there are risk factors<ref name="BBDstatins2">{{Cite journal |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 |postscript =<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}, which cites
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| *{{cite PMID|15249516}}</ref>
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| | 100 mg/dL, 5.55 mmol/dL<ref name="BBDstatins2"/>
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| |-
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| | moderately high
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| | a 10-20% risk of heart attack in 10 years and two or more risk factors
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| | 100 mg/dL, 5.55 mmol/dL<ref name="BBDstatins2"/>
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| | 130 mg/dL, 7.21 mmol/dL<ref name="BBDstatins2"/>
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| |-
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| | moderate
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| | less than 10% risk of heart attack in 10 years and two or more risk factors
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| | 130 mg/dL, 7.21 mmol/dL<ref name="BBDstatins2"/>
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| | 160 mg/dL, 8.88 mmol/dL<ref name="BBDstatins2"/>
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| |-
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| | low
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| | No risk factors or only one
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| | 160 mg/dL, 8.88 mmol/dL<ref name="BBDstatins2"/>
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| | 190 mg/dL, 10.5 mmol/dL<ref name="BBDstatins2"/>
| |
| |-
| |
| |}
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| Cholesterol is measured as milligrams per deciliter (mg/dL) of blood in the United States and some other countries. In the United Kingdom, most European countries, and Canada, millimoles per liter of blood (mmol/L) is the measure.<ref name="MayoClinic">[http://www.mayoclinic.com/health/high-blood-cholesterol/DS00178/DSECTION=tests-and-diagnosis High Cholesterol – Tests and Diagnosis], Mayo Clinic staff. Retrieved 2013-03-09.</ref>
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| For healthy adults, the UK National Health Service recommends total cholesterol of 5 mmol/L or less, and low-density lipoprotein cholesterol (LDL) of 3 mmol/L or less. For people at high risk of cardiovascular disease, the recommendation for total cholesterol is 4 mmol/L or less, and 2 mmol/L or less for LDL.<ref name="NHScholesterol">[http://www.nhs.uk/Conditions/Cholesterol/Pages/Diagnosis.aspx Diagnosing High Cholesterol], NHS Choices. Retrieved 2013-03-09.</ref>
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| In the United States, the National Heart, Lung, and Blood Institute within the National Institutes of Health classifies total cholesterol of less than 200 mg/dL as “desirable,” 200 to 239 mg/dL as “borderline high,” and 240 mg/dL or more as “high.”<ref name="NHLBIcholesterol">[http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf ATP III Guidelines At-A-Glance Quick Desk Reference], National Cholesterol Education Program. Retrieved 2013-03-09.</ref>
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| There is not an absolute cutoff between normal and abnormal cholesterol levels and interpretation of values needs to be made in relation to other health conditions and risk factors.
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| Higher levels of total cholesterol increase the risk of cardiovascular disease, particularly coronary heart disease. Levels of LDL or non-HDL cholesterol both predict future coronary heart disease, which is the better predictor is disputed.<ref name = "ESC 2011">{{cite journal |author=Reiner Z, Catapano AL, De Backer G, ''et al.'' |title=ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) |journal=Eur. Heart J. |volume=32 |issue=14 |pages=1769–818 |date=July 2011 |pmid=21712404 |doi=10.1093/eurheartj/ehr158 |url=}}</ref> High levels of small dense LDL may be particularly adverse, although measurement of small dense LDL is not advocated for risk prediction.<ref name = "ESC 2011" /> In the past LDL and VLDL levels were rarely measured directly due to cost. Levels of fasting [[triglyceride]]s were taken as an indicator of VLDL levels (generally about 45% of fasting triglycerides is composed of VLDL), while LDL was usually estimated by the Friedewald formula:
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|
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| LDL <math>\approx</math> total cholesterol - HDL - (0.2 x fasting triglycerides).
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| However, this equation is not valid on non-fasting blood samples or if fasting triglycerides are elevated >4.5 mmol/L (> ∼400 mg/dL). Recent guidelines have therefore advocated the use of direct methods for measurement of LDL wherever possible.<ref name = "ESC 2011"/>
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| It may be useful to measure all lipoprotein subfractions ( [[Very-low-density lipoprotein|VLDL]], [[Intermediate density lipoprotein|IDL]], [[low-density lipoprotein|LDL]], [[High-density lipoprotein|HDL]]) when assessing hypercholesterolemia and measurement of [[apolipoproteins]] and [[lipoprotein (a)]] can also be of value.<ref name = "ESC 2011"/> Genetic screening is now advised if a form of familial hypercholesterolemia is suspected.<ref name = "ESC 2011"/>
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| ===Classification===
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| {{main|Hyperlipidemia}}
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| Classically, hypercholesterolemia was categorized by lipoprotein [[electrophoresis]] and the [[hyperlipidemia#Classification|Fredrickson classification]]. Newer methods, such as "lipoprotein subclass analysis" have offered significant improvements in understanding the connection with atherosclerosis progression and clinical consequences.
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| If the hypercholesterolemia is hereditary ([[familial hypercholesterolemia]]), there is more
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| often a [[Family history (medicine)|family history]] of premature, earlier onset atherosclerosis.
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| ==Screening==
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| The [[U.S. Preventive Services Task Force]] (USPSTF) strongly recommends routine screening for men 35 years and older and women 45 years and older for lipid disorders and the treatment of abnormal lipids in people who are at increased risk of coronary heart disease. They also recommend routinely screening men aged 20 to 35 years and women aged 20 to 45 years if they have other risk factors for [[coronary heart disease]].<ref name=Pignone>{{cite web|title=Screening for Lipid Disorders: Recommendations and Rationale|author=U.S. Preventive Services Task Force|url=http://www.uspreventiveservicestaskforce.org/uspstf/uspschol.htm|accessdate=2010-11-04}}</ref> In Canada screening is recommended for men 40 and older and women 50 and older.<ref>{{cite journal|last=Genest|first=J|coauthors=Frohlich, J, Fodor, G, McPherson, R, Working Group on Hypercholesterolemia and Other, Dyslipidemias|title=Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update|journal=Canadian Medical Association Journal |date=2003-10-28|volume=169|issue=9|pages=921–4|pmid=14581310|pmc=219626}}</ref> In those with normal cholesterol levels screening is recommended once every five years.<ref>{{cite journal|last=National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel|first=III)|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) final report|journal=Circulation|date=2002-12-17|volume=106|issue=25|pages=3143–421|pmid=12485966}}</ref> Once people are on a statin further testing provides little benefit except to possibly determine compliance with treatment.<ref>{{cite journal|last=Spector|first=R|coauthors=Snapinn, SM|title=Statins for secondary prevention of cardiovascular disease: the right dose|journal=Pharmacology|year=2011|volume=87|issue=1–2|pages=63–9|pmid=21228612|doi=10.1159/000322999}}</ref>
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| ==Treatment==
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| Recommendations for both [[primary prevention]]<ref name=pmid16620402>{{cite journal
| |
| |last=Pignone|first=M
| |
| |title=Primary prevention: dyslipidaemia
| |
| |journal=Clin Evid
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| |issue=14
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| |pages=142–50
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| |pmid=16620402
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| |year=2005
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| |url=http://clinicalevidence.com/ceweb/conditions/cvd/0215/0215.jsp
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| |accessdate=2010-11-04}}</ref> and [[secondary prevention]]<ref name=pmid16973010>{{cite journal
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| |last=Gami|first=A
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| |title=Secondary prevention of ischaemic cardiac events
| |
| |journal=Clin Evid
| |
| |issue=15|pages=195–228|pmid=16973010
| |
| |year=2006
| |
| |url=http://clinicalevidence.com/ceweb/conditions/cvd/0206/0206_guidelines.jsp
| |
| |accessdate=2010-11-04}}</ref> have been published. For those at high risk a combination of lifestyle modification and [[statins]] has been shown to decrease mortality.<ref name="BMJ2008"/>
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| ===Lifestyle===
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| Lifestyle changes recommended for those with high cholesterol include: smoking cessation, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight. A diet that emphasizes low-cholesterol foods, restricts [[saturated fats]],<ref name="BMJ2008"/> and avoids trans fat is also recommended.<ref name="urlHow Can I Lower High Cholesterol?">{{cite web | url = http://www.heart.org/idc/groups/heart-public/@wcm/@hcm/documents/downloadable/ucm_300460.pdf | title = How Can I Lower High Cholesterol | author = | authorlink = | coauthors = | date = | format = | work = | publisher = American Heart Association | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2011-04-03}}</ref> In strictly controlled surroundings, dietary changes can reduce cholesterol levels by 15 percent. In practice, dietary advice can provide a modest decrease in cholesterol levels and may be sufficient in the treatment of mildly elevated cholesterol.<ref name=Tang1998>{{cite journal|author=Tang JL, Armitage JM, Lancaster T, Silagy CA, Fowler GH, Neil HA|title=Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects|journal=BMJ|volume=316|issue=7139|pages=1213–20|year=1998|pmid=9552999|pmc=28525|url=http://www.bmj.com/cgi/content/abstract/316/7139/1213|accessdate=2010-11-04|doi=10.1136/bmj.316.7139.1213}}</ref>
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| ===Medication===
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| [[Statins]] (or HMG-CoA reductase inhibitors) are commonly used to treat hypercholesterolemia if diet is ineffective. Other agents that may be used include: [[fibrate]]s, [[nicotinic acid]] and [[cholestyramine]].<ref name=NICE67>{{NICE|67|Lipid modification|2008}}</ref> These however are only recommended if statins are not tolerated.<ref name=NICE67/> Statins can reduce total cholesterol by approximately 50% in the majority of people;<ref name = "ESC 2011"/> effects appear similar regardless of the statin used.<ref name=CMAJ11/> While statins are effective in decreasing mortality in those who have had previous [[cardiovascular disease]], there is debate over whether or not they are effective in those with high cholesterol but no other health problems.<ref name=AIM2010/> One review did not find a mortality benefit in those at high-risk but without prior cardiovascular disease.<ref name=AIM2010>{{cite journal|journal=Arch Intern Med|title=Statins and All-Cause Mortality in High-Risk Primary Prevention: A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants|year=2010|author=Ray et al|volume=170|issue=12|url=http://archinte.ama-assn.org/cgi/content/full/170/12/1024|accessdate=2010-11-04|doi=10.1001/archinternmed.2010.182|pmid=20585067|last2=Seshasai|first2=S. R. K.|last3=Erqou|first3=S.|last4=Sever|first4=P.|last5=Jukema|first5=J. W.|last6=Ford|first6=I.|last7=Sattar|first7=N.|pages=1024–31}}</ref> Other reviews concluded that there is a mortality benefit<ref name=CMAJ11>{{cite journal|last=Tonelli|first=M|coauthors=Lloyd, A, Clement, F, Conly, J, Husereau, D, Hemmelgarn, B, Klarenbach, S, McAlister, FA, Wiebe, N, Manns, B, for the Alberta Kidney Disease, Network|title=Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis|journal=CMAJ : Canadian Medical Association |date=2011-11-08|volume=183|issue=16|pages=E1189–E1202|pmid=21989464|doi=10.1503/cmaj.101280|pmc=3216447}}</ref><ref>{{cite journal|last=Mills|first=EJ|coauthors=Wu, P, Chong, G, Ghement, I, Singh, S, Akl, EA, Eyawo, O, Guyatt, G, Berwanger, O, Briel, M|title=Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials|journal=QJM : monthly journal of the Association of Physicians|date=February 2011|volume=104|issue=2|pages=109–24|pmid=20934984|doi=10.1093/qjmed/hcq165}}</ref><ref>{{cite journal|author=Cholesterol Treatment Trialists' (CTT) Collaborators | title=The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials| journal=Lancet | year=2012| volume=Online first | doi=10.1016/S0140-6736(12)60367-5}}</ref> but concerns regarding the quality of the evidence persist.<ref name=Cochrane11/> With respect to [[quality of life]] there is limited evidence of improvement when statins are used in people without existing cardiovascular disease (i.e. for primary prevention).<ref name=Cochrane11>{{cite journal |author=Taylor F, Ward K, Moore TH, ''et al.'' |title=Statins for the primary prevention of cardiovascular disease |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004816 |year=2011 |pmid=21249663 |doi=10.1002/14651858.CD004816.pub4 |url= |editor1-last=Taylor |editor1-first=Fiona}}</ref> Statins decrease cholesterol in children with hypercholesterolemia but no studies as of 2010 show improved clinical outcomes<ref name=Leben2010>{{cite journal|author=Lebenthal Y, Horvath A, Dziechciarz P, Szajewska H, Shamir R|title=Are treatment targets for hypercholesterolemia evidence based? Systematic review and meta-analysis of randomised controlled trials|journal=Arch Dis Child|volume=95|issue=9|pages=673–80|year=2010|pmid=20515970|doi=10.1136/adc.2008.157024|url=}}</ref> and diet is the mainstay of therapy in childhood.<ref name = "ESC 2011"/>
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| ===Guidelines===
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| Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The [[American College of Physicians]] has addressed hypercholesterolemia in patients with [[diabetes]].<ref name=pmid15096336>{{cite journal|doi=10.1059/0003-4819-140-8-200404200-00012|author=Snow V, Aronson M, Hornbake E, Mottur-Pilson C, Weiss K|title=Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians|journal=Ann Intern Med|volume=140|issue=8|pages=644–9|year=2004|pmid=15096336|url=http://www.annals.org/cgi/content/full/140/8/644|accessdate=2010-11-04}}</ref> Their four recommendations are:
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| # 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.
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| # 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.
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| # 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").<ref name=pmid15096337>{{cite journal|doi=10.1059/0003-4819-140-8-200404200-00013|last1=Vijan|first1=S|last2=Hayward|first2=RA|last3=American College Of|first3=Physicians|title=Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians|journal=Ann Intern Med|volume=140|issue=8|pages=650–8|year=2004|pmid=15096337|url=http://www.annals.org/cgi/content/full/140/8/650|accessdate=2010-11-04}}</ref>
| |
| # 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.
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| The [[National Cholesterol Education Program]] revised their guidelines;<ref name=pmid15358046>{{cite journal|author=Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ|title=Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines|journal=J Am Coll Cardiol|volume=44|issue=3|pages=720–32|year=2004|pmid=15358046|doi=10.1016/j.jacc.2004.07.001|url=}}</ref> however, their 2004 revisions have been criticized for use of nonrandomized, observational data.<ref name=pmid17015870>{{cite journal|last1=Hayward|first1=RA|last2=Hofer|first2=TP|last3=Vijan|first3=S|title=Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem|journal=Ann Intern Med|volume=145|issue=7|pages=520–30|year=2006|pmid=17015870|url=|doi=10.7326/0003-4819-145-7-200610030-00010}}</ref>
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| 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.<ref name=NICE67/>
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| | |
| The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) published the ESC/EAS Guidelines for the management of dyslipidaemias in 2011.<ref name ="ESC 2011"/>
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| ===Alternative medicine===
| |
| According to a survey in 2002, [[alternative medicine]] was used in an attempt to treat cholesterol by 1.1% of U.S. adults. Consistent with previous surveys, this one found that the majority of individuals (i.e., 55%) used it in conjunction with [[conventional medicine]].<ref name=NCCAM>{{cite journal |author=Barnes PM, Powell-Griner E, McFann K, Nahin RL |title=Complementary and Alternative Medicine Use Among Adults: United States, 2002 |journal=Advance Data from Vital and Health Statistics |issue=343 |date=May 27, 2004 |format=PDF |pages=6–9 |url=http://nccam.nih.gov/news/report.pdf |accessdate=2010-11-04 |version=http://nccam.nih.gov/news/2004/052704.htm }}</ref>
| |
| A review of trials of [[phytosterols]] and/or phytostanols reported an average of 9% lowering of LDL-cholesterol.<ref name=PMID1909>{{cite journal |author=Demonty I, 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=[[J Nutr]] |volume=139 |issue=2 |date=February 2009 |pages=271–84 |pmid=19091798 |doi=10.3945/jn.108.095125 }}</ref> In 2000 the Food and Drug Administration approved the labeling of foods containing specified amounts of phytosterol esters or phytostanol esters as cholesterol lowering; in 2003 an FDA Interim Health Claim Rule extended that label claim to foods or dietary supplements delivering more than 0.8 grams/day of phytosterols or phytostanols. Some researchers, however, are concerned about diet supplementation with plant sterol esters and draw attention to lack of long-term safety data.<ref name=Wein2009>{{cite journal|author=Weingärtner O. et al|title=Controversial role of plant sterol esters in the management of hypercholesterolaemia|journal=European Heart Journal |volume=30 |issue=4 |pages=404–9 |year=2009 |pmid=19158117 |pmc=2642922 |doi=10.1093/eurheartj/ehn580 |url=http://eurheartj.oxfordjournals.org/cgi/content/extract/30/4/404|last2=Bohm|first2=M.|last3=Laufs|first3=U. }}</ref>
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| ==Epidemiology==
| |
| Rates of high total cholesterol in the United States in 2010 are just over 13% down from 17% in 2000.<ref>{{cite web|last=Carrol|first=Margaret|title=Total and High-density Lipoprotein Cholesterol in Adults: National Health and Nutrition Examination Survey, 2009–2010|url=http://www.cdc.gov/nchs/data/databriefs/db92.pdf|publisher=CDC|date=April 2012}}</ref>
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| Average total cholesterol in the United Kingdom is 5.9 mmol/L while in rural China and Japan average total cholesterol is 4 mmol/L.<ref name="BMJ2008"/> Rates of coronary artery disease are high in Great Britain, but low in rural China and Japan.<ref name="BMJ2008"/>
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| ==References==
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| {{Reflist|3}}
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| {{Lipidemias}}
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| [[Category:Lipid metabolism disorders]]
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| [[Category:Medical conditions related to obesity]]
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