View source for Hypercholesterolemia

{{short description|High levels of cholesterol in the blood}}
{{Infobox medical condition (new)
| name = Hypercholesterolemia
| image = Lipemic plasma.jpg
| caption = 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 altered serum lipid levels, while the bag obtained from a normal donor contains regular serum lipid levels.
| pronounce =
| synonyms = Hypercholesterolaemia, high cholesterol
| field = [[Cardiology]]
| symptoms =
| complications = [[Atherosclerosis]], [[thrombosis]], [[embolism]], [[heart attack]], [[stroke]], [[coronary thrombosis]], [[fat embolism]], [[cardiovascular disease|cardiovascular]] and [[coronary heart disease]]
| onset =
| duration =
| types =
| causes = Poor diet, [[junk food]], [[fast food]], [[diabetes]], [[alcoholism]], [[monoclonal gammopathy]], [[Kidney dialysis|dialysis]] therapy, [[nephrotic syndrome]], [[hypothyroidism]], [[Cushing's syndrome]], [[anorexia nervosa]]
| risks =
| diagnosis =
| differential = [[Hyperlipidemia]], [[hypertriglyceridemia]]
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
<!-- Definition and symptoms -->
'''Hypercholesterolemia''', also called '''high cholesterol''', is the presence of high levels of [[cholesterol]] in the blood.<ref name=Durrington>{{cite journal | vauthors = Durrington P | title = Dyslipidaemia | journal = Lancet | volume = 362 | issue = 9385 | pages = 717–731 | date = August 2003 | pmid = 12957096 | doi = 10.1016/S0140-6736(03)14234-1 | s2cid = 208792416 }}</ref> It is a form of [[hyperlipidemia]] (high levels of [[lipid]]s in the blood), hyperlipoproteinemia (high levels of [[lipoprotein]]s in the blood), and [[dyslipidemia]] (any abnormalities of lipid and lipoprotein levels in the blood).<ref name=Durrington/>

<!-- Cause -->
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 type 2|type 2 diabetes]] and [[hypothyroidism|an underactive thyroid]].<ref name=Durrington/>

<!-- Mechanism -->
Cholesterol is one of three major classes of lipids produced and used by all animal cells to form membranes. Plant cells manufacture phytosterols (similar to cholesterol) but in small quantities.<ref>{{Cite journal| vauthors = Behrman EJ, Gopalan V |date= December 2005 |title=Cholesterol and Plants|journal=Journal of Chemical Education|volume=82|issue=12|pages=1791|doi=10.1021/ed082p1791|bibcode=2005JChEd..82.1791B|issn=0021-9584}}</ref> Cholesterol is the precursor of the [[steroid hormone]]s and [[bile acid]]s. 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 | vauthors = Biggerstaff KD, Wooten JS | title = Understanding lipoproteins as transporters of cholesterol and other lipids | journal = Advances in Physiology Education | volume = 28 | issue = 1–4 | pages = 105–106 | date = December 2004 | pmid = 15319192 | doi = 10.1152/advan.00048.2003 | s2cid = 30197456 }}</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 | vauthors = Carmena R, Duriez P, Fruchart JC | title = Atherogenic lipoprotein particles in atherosclerosis | journal = Circulation | volume = 109 | issue = 23 Suppl 1 | pages = III2–III7 | date = June 2004 | pmid = 15198959 | doi = 10.1161/01.CIR.0000131511.50734.44 | doi-access = free }}</ref> In contrast, higher HDL cholesterol levels are protective.<ref>{{cite journal | vauthors = Kontush A, Chapman MJ | title = Antiatherogenic small, dense HDL--guardian angel of the arterial wall? | journal = Nature Clinical Practice. Cardiovascular Medicine | volume = 3 | issue = 3 | pages = 144–153 | date = March 2006 | pmid = 16505860 | doi = 10.1038/ncpcardio0500 | s2cid = 27738163 }}</ref>

<!-- Treatment, prevention and epidemiology -->
Avoiding [[trans fats]] and replacing [[saturated fats]] in adult diets with [[polyunsaturated fats]] are recommended dietary measures to reduce total blood cholesterol and LDL in adults.<ref>{{cite web | title=Healthy diet – Fact sheet N°394 | url=https://www.who.int/mediacentre/factsheets/fs394/en/ | work=[[World Health Organization]] | date=September 2015 | access-date=July 6, 2016 }}</ref><ref name=BMJ2015/> In people with very high cholesterol (e.g., familial hypercholesterolemia), diet is often not sufficient to achieve the desired lowering of LDL, and lipid-lowering [[medications]] are usually required.<ref name=Ito2011>{{cite journal | vauthors = 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 = Journal of Clinical Lipidology | volume = 5 | issue = 3 Suppl | pages = S38–S45 | date = June 2011 | pmid = 21600528 | doi = 10.1016/j.jacl.2011.04.001 }}</ref> If necessary, other treatments such as LDL [[apheresis]] or even surgery (for particularly severe subtypes of familial hypercholesterolemia) are performed.<ref name = Ito2011/> About 34 million adults in the United States have high blood cholesterol.<ref name=GHR2016>{{cite web|title=Hypercholesterolemia|url=https://ghr.nlm.nih.gov/condition/hypercholesterolemia#expand-collapse-start|website=Genetics Home Reference|access-date=16 May 2016}}</ref>
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==Signs and symptoms==

[[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]].]]

Although hypercholesterolemia itself is [[asymptomatic]], longstanding elevation of serum cholesterol can lead to [[atherosclerosis]] (build-up of fatty plaques in the arteries, so-called 'hardening of the arteries').<ref name="BMJ2008">{{cite journal | vauthors = Bhatnagar D, Soran H, Durrington PN | title = Hypercholesterolaemia and its management | journal = BMJ | volume = 337 | pages = a993 | date = August 2008 | pmid = 18719012 | doi = 10.1136/bmj.a993 | s2cid = 5339837 }}</ref> Over decades, elevated serum cholesterol contributes to the formation of [[atheroma|atheromatous plaques]] in the arteries. This can lead to progressive [[stenosis|narrowing]] of the involved arteries. Alternatively, smaller plaques may rupture and cause a clot to form and obstruct blood flow.<ref>{{cite journal | vauthors = Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R | title = Concept of vulnerable/unstable plaque | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 30 | issue = 7 | pages = 1282–1292 | date = July 2010 | pmid = 20554950 | doi = 10.1161/ATVBAHA.108.179739 | doi-access =  }}</ref> A sudden blockage of a coronary artery may result in a heart attack. A blockage of an artery supplying the brain can cause a stroke. If the development of the stenosis or occlusion is gradual, the blood supply to the tissues and organs slowly diminishes until organ function becomes impaired. At this point 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]] or [[paresthesia|numbness or tingling]], usually on one side of the body. Insufficient blood supply to the heart may cause [[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 | vauthors = Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, Houston-Miller N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, Reed J, Washington R, Smith SC | display-authors = 6 | 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 | volume = 97 | issue = 18 | pages = 1876–1887 | date = May 1998 | pmid = 9603549 | doi = 10.1161/01.CIR.97.18.1876 | doi-access = free }}</ref>

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 | vauthors = Shields C, Shields J |title=Eyelid, conjunctival, and orbital tumors: atlas and textbook |publisher=Lippincott Williams & Wilkins |location=Hagerstown, Maryland |year=2008 |isbn=978-0-7817-7578-6 }}</ref> [[arcus senilis]] (white or gray discoloration of the peripheral [[cornea]]),<ref name=Zech2008>{{cite journal | vauthors = Zech LA, Hoeg JM | title = Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia | journal = Lipids in Health and Disease | volume = 7 | issue = 1 | pages = 7 | date = March 2008 | pmid = 18331643 | pmc = 2279133 | doi = 10.1186/1476-511X-7-7 | doi-access = free }}</ref> and [[xanthoma]]ta (deposition of yellowish cholesterol-rich material) of the [[tendon]]s, especially of the fingers.<ref name=Andrews2006>{{cite book | vauthors = James WD, Berger TG |title=Andrews' Diseases of the Skin: Clinical Dermatology |publisher=Saunders Elsevier|year=2006|pages=530–32 |isbn=978-0-7216-2921-6 }}</ref><ref name=Rapini2007>{{cite book | vauthors = Rapini RP, Bolognia JL, Jorizzo JL |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis, Missouri |year=2007 |pages=1415–16 |isbn=978-1-4160-2999-1 }}</ref> Type III hyperlipidemia may be associated with xanthomata of the palms, knees and elbows.<ref name=Andrews2006/>

==Causes==
[[File:Cholesterol.svg|thumb|Formula structure of [[cholesterol]]]]
Hypercholesterolemia is typically due to a combination of environmental and genetic factors.<ref name="BMJ2008"/> Environmental factors include weight, [[Dieting|diet]], and [[Stress (biology)|stress]].<ref name=BMJ2008/><ref name="Calderon_1999">{{cite journal | vauthors = Calderon R, Schneider RH, Alexander CN, Myers HF, Nidich SI, Haney C | title = Stress, stress reduction and hypercholesterolemia in African Americans: a review | journal = Ethnicity & Disease | volume = 9 | issue = 3 | pages = 451–62 | date = 1999 | pmid = 10600068 | doi = | url = }}</ref> [[Loneliness]] is also a risk factor.<ref name="Cacioppo_2010">{{cite journal | vauthors = Hawkley LC, Cacioppo JT | title = Loneliness matters: a theoretical and empirical review of consequences and mechanisms | journal = Annals of Behavioral Medicine | volume = 40 | issue = 2 | pages = 218–227 | date = October 2010 | pmid = 20652462 | pmc = 3874845 | doi = 10.1007/s12160-010-9210-8 }}</ref>

===Diet===
Diet affects blood cholesterol, but the size of this effect varies between individuals.<ref name="ReferenceA">{{cite journal | vauthors = Mannu GS, Zaman MJ, Gupta A, Rehman HU, Myint PK | title = Evidence of lifestyle modification in the management of hypercholesterolemia | journal = Current Cardiology Reviews | volume = 9 | issue = 1 | pages = 2–14 | date = February 2013 | pmid = 22998604 | pmc = 3584303 | doi = 10.2174/157340313805076313 }}</ref><ref>{{cite journal | vauthors = 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 = The American Journal of Clinical Nutrition | volume = 65 | issue = 6 | pages = 1747–1764 | date = June 1997 | pmid = 9174470 | doi = 10.1093/ajcn/65.6.1747 | doi-access = free }}</ref>

A diet high in sugar or saturated fats increases total cholesterol and LDL.<ref>{{cite journal | vauthors = DiNicolantonio JJ, Lucan SC, O'Keefe JH | title = The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease | journal = Progress in Cardiovascular Diseases | volume = 58 | issue = 5 | pages = 464–472 | date = 2016 | pmid = 26586275 | pmc = 4856550 | doi = 10.1016/j.pcad.2015.11.006 }}</ref> [[Trans fats]] have been shown to reduce levels of [[high-density lipoprotein]] while increasing levels of LDL.<ref name="Ascherio_1997">{{cite journal | vauthors = Ascherio A, Willett WC | title = Health effects of trans fatty acids | journal = The American Journal of Clinical Nutrition | volume = 66 | issue = 4 Suppl | pages = 1006S–1010S | date = October 1997 | pmid = 9322581 | doi = 10.1093/ajcn/66.4.1006S | doi-access = free }}</ref>

A 2016 review found tentative evidence that dietary cholesterol is associated with higher blood cholesterol.<ref>{{cite journal | vauthors = Grundy SM | title = Does Dietary Cholesterol Matter? | journal = Current Atherosclerosis Reports | volume = 18 | issue = 11 | pages = 68 | date = November 2016 | pmid = 27739004 | doi = 10.1007/s11883-016-0615-0 | s2cid = 30969287 }}</ref> As of 2018 there appears to be a modest positive, dose-related relationship between cholesterol intake and LDL cholesterol.<ref>{{cite journal | vauthors = Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC | title = Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol | journal = The American Journal of Clinical Nutrition | volume = 109 | issue = 1 | pages = 7–16 | date = January 2019 | pmid = 30596814 | doi = 10.1093/ajcn/nqy273 | doi-access = free }}</ref>

===Medical conditions and treatments===
A number of other conditions can also increase cholesterol levels including [[diabetes mellitus type 2]], [[obesity]], [[alcohol (drug)|alcohol]] use, [[monoclonal gammopathy]], [[Kidney dialysis|dialysis]] therapy, [[nephrotic syndrome]], [[hypothyroidism]], [[Cushing's syndrome]] and [[anorexia nervosa]].<ref name=BMJ2008/> Several medications and classes of medications may interfere with lipid metabolism: [[thiazide diuretics]], [[ciclosporin]], [[glucocorticoids]], [[beta blockers]], [[retinoic acid]], [[antipsychotic]]s,<ref name=BMJ2008/> certain [[anticonvulsant]]s and medications for HIV as well as [[interferon]]s.<ref name="Herink">{{Cite book | vauthors = Herink M, Ito MK |chapter=Medication Induced Changes in Lipid and Lipoproteins |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK326739/|title=Endotext|date=2000-01-01|publisher=MDText.com, Inc.| veditors =  De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R |location=South Dartmouth (MA)|pmid=26561699 }}</ref>

===Genetics===
Genetic contributions typically arise from the combined effects of multiple genes, known as "polygenic," although in certain cases, they may stem from a single gene defect, as seen in [[familial hypercholesterolemia]].<ref name=BMJ2008/> In familial hypercholesterolemia, mutations may be present in the [[APOB]] gene ([[autosomal dominant]]), 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 |access-date=5 December 2013 }}</ref> Familial hypercholesterolemia affects about one in 250 individuals.<ref name="pmid28864697">{{cite journal | vauthors = Akioyamen LE, Genest J, Shan SD, Reel RL, Albaum JM, Chu A, Tu JV | title = Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis | journal = BMJ Open | volume = 7 | issue = 9 | pages = e016461 | date = September 2017 | pmid = 28864697 | pmc = 5588988 | doi = 10.1136/bmjopen-2017-016461 }}</ref>

The [[Litvaks|Lithuanian Jewish]] population may exhibit a genetic [[founder effect]].<ref>{{cite journal|pmc=1216062|title=A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases|publisher=[[American Society of Human Genetics]] via [[PubMed]]|pmid=15208782|doi=10.1086/423146|volume=75|issue=2|date=August 2004|journal=Am. J. Hum. Genet.|pages=282–93 | last1 = Slatkin | first1 = M}}</ref> One variation, G197del LDLR which is implicated in familial hypercholesterolemia, has been dated to the 14th century.<ref>{{citation|last=Durst |first=Ronen |others=Roberto Colombo, Shoshi Shpitzen, Liat Ben Avi, et al. |title=Recent Origin and Spread of a Common Lithuanian Mutation, G197del LDLR, Causing Familial Hypercholesterolemia: Positive Selection Is Not Always Necessary to Account for Disease Incidence among Ashkenazi Jews |journal=American Journal of Human Genetics |volume=68 |number=5 |date=May 2001 |pages=1172–1188 |doi=10.1086/320123|pmid=11309683 |pmc=1226098 }}</ref> The {{Clarify | text = utility| date = March 2024 | reason = Utility for research, for treatment, for what?  This unclear sentence probably isn't supported by the reference.}} of these variations has been the subject of debate.<ref>{{cite web|url=http://www.khazaria.com/genetics/abstracts-diseases.html|title=Jewish Genetics, Part 3: Jewish Genetic Diseases (Mediterranean Fever, Tay–Sachs, pemphigus vulgaris, Mutations)|website=www.khazaria.com|access-date=18 October 2018}}</ref>

==Diagnosis==
{{See also|High-density lipoprotein#Recommended ranges|Low-density lipoprotein#Normal ranges}}
{| class="wikitable" style="float:right; width:30em; border:solid 1px #999999; margin:0 0 1em 1em;"
|+Interpretation of cholesterol levels
|-
! Cholesterol type
! mmol/L
! mg/dL
! Interpretation
|-
|rowspan="3"| total cholesterol
| <5.2
| <200
| 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 |journal = Best Buy Drugs |page = 9 |url = http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/StatinsUpdate-FINAL.pdf |access-date = 27 March 2013 }} which cites
* {{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 |author-link1=United States Department of Health and Human Services |author2=National Heart Lung and Blood Institute |author-link2=National Heart, Lung, and Blood Institute |author3=National Institutes of Health |author-link3=National Institutes of Health |work=nhlbi.nih.gov |date=June 2005 |access-date=27 March 2013 |archive-url=https://web.archive.org/web/20130401072344/http://www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm |archive-date=1 April 2013 |url-status=dead }}</ref>
|-
| 5.2–6.2
| 200–239
| Borderline<ref name="BBDstatins"/>
|-
| >6.2
| >240
| High<ref name="BBDstatins"/>
|-
|rowspan="5"|LDL cholesterol
| <2.6
| <100
| Most desirable<ref name="BBDstatins"/>
|-
| 2.6–3.3
| 100–129
| Good<ref name="BBDstatins"/>
|-
| 3.4–4.1
| 130–159
| Borderline high<ref name="BBDstatins"/>
|-
| 4.1–4.9
| 160–189
| High and undesirable<ref name="BBDstatins"/>
|-
| >4.9
| >190
| Very high<ref name="BBDstatins"/>
|-
| rowspan="3"|HDL cholesterol
| <1.0
| <40
| Undesirable; risk increased<ref name="BBDstatins"/>
|-
| 1.0–1.5
| 41–59
| Okay, but not optimal<ref name="BBDstatins"/>
|-
| >1.55
| >60
| Good; risk lowered<ref name="BBDstatins"/>
|}
Cholesterol is measured in milligrams per deciliter (mg/dL) of blood in the United States and some other countries. In the United Kingdom, most European countries, and Canada, millimoles per liter of blood (mmol/L) is the measure.<ref name="MayoClinic">{{cite web | title=Diagnosis and treatment | website=Mayo Clinic | date=2023-01-11 | url=https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/diagnosis-treatment/drc-20350806 | access-date=2024-03-16 | archiveurl = https://web.archive.org/web/20240313184442/https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/diagnosis-treatment/drc-20350806 | archivedate = 2024-03-13 | url-status = live}}</ref>

For healthy adults, the UK National Health Service recommends upper limits of total cholesterol of 5&nbsp;mmol/L, and low-density lipoprotein cholesterol (LDL) of 3&nbsp;mmol/L. For people at high risk of cardiovascular disease, the recommended limit for total cholesterol is 4&nbsp;mmol/L, and 2&nbsp;mmol/L for LDL.<ref name="NHScholesterol">[http://www.nhs.uk/Conditions/Cholesterol/Pages/Diagnosis.aspx Diagnosing High Cholesterol], NHS Choices. Retrieved 2013-03-09.</ref>

In the United States, the National Heart, Lung, and Blood Institute within the National Institutes of Health classifies total cholesterol of less than 200&nbsp;mg/dL as "desirable", 200 to 239&nbsp;mg/dL as "borderline high", and 240&nbsp;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>

There is no absolute cutoff between normal and abnormal cholesterol levels, and values must be considered in relation to other health conditions and risk factors.<ref>
{{cite web | last1 = Davidson | first1 = Michael H. | last2 = Pradeep | first2 = Pallavi | title = Hormonal and Metabolic Disorders | website = MSD Manual Consumer Version | date = 2023-07-03 | url = https://www.msdmanuals.com/home/hormonal-and-metabolic-disorders/cholesterol-disorders/dyslipidemia | access-date = 2024-03-16 | archiveurl = https://web.archive.org/web/20231114081311/https://www.msdmanuals.com/home/hormonal-and-metabolic-disorders/cholesterol-disorders/dyslipidemia | archivedate = 2023-11-14 | url-status = live | quote = Although there is no natural cutoff between normal and abnormal cholesterol levels, ...}}</ref><ref>
{{cite web | title = What Your Cholesterol Levels Mean | website = www.heart.org | date = 2017-11-16 | url = https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/what-your-cholesterol-levels-mean | access-date = 2024-03-16 | archiveurl = https://web.archive.org/web/20240226103854/https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/what-your-cholesterol-levels-mean | archivedate = 2024-02-26 | url-status = live | quote = While cholesterol levels above "normal ranges" are important in your overall cardiovascular risk, like HDL and LDL cholesterol levels, your total blood cholesterol level should be considered in context with your other known risk factors.}}</ref><ref>
{{cite journal | display-authors = 4 | last1 = Nantsupawat | first1 = Nopakoon | last2 = Booncharoen | first2 = Apaputch | last3 = Wisetborisut | first3 = Anawat | last4 = Jiraporncharoen | first4 = Wichuda | last5 = Pinyopornpanish | first5 = Kanokporn | last6 = Chutarattanakul | first6 = Lalita | last7 = Angkurawaranon | first7 = Chaisiri | title = Appropriate Total cholesterol cut-offs for detection of abnormal LDL cholesterol and non-HDL cholesterol among low cardiovascular risk population | journal = Lipids in Health and Disease | volume = 18 | date = 2019-01-26 | issue = 1 | issn = 1476-511X | pmid = 30684968 | pmc = 6347761 | doi = 10.1186/s12944-019-0975-x | page = 28 | doi-access = free | quote = The current appropriate TC cutoff to determine whether patients need further investigation and assessment is between 200 and 240 mg/dL [1, 17, 18]. However, the appropriate cut-off point for the younger population who may have low cardiovascular risk has not been examined extensively in the literature. A recent study suggests that a TC cut off point of between 200 and 240 may not be appropriate in identifying high LDL-C levels in apparently healthy people.}}</ref>

Higher levels of total cholesterol increase the risk of cardiovascular disease, particularly coronary heart disease.<ref>{{cite journal | vauthors = Peters SA, Singhateh Y, Mackay D, Huxley RR, Woodward M | title = Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: A systematic review and meta-analysis | journal = Atherosclerosis | volume = 248 | pages = 123–131 | date = May 2016 | pmid = 27016614 | doi = 10.1016/j.atherosclerosis.2016.03.016 }}</ref> 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 | vauthors = Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D | display-authors = 6 | 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 = European Heart Journal | volume = 32 | issue = 14 | pages = 1769–1818 | date = July 2011 | pmid = 21712404 | doi = 10.1093/eurheartj/ehr158 | doi-access = free }}</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.<!--These references only talked about LDL direct measurement costs.--><ref>
{{cite journal | last = Superko | first = H. Robert | title = Advanced Lipoprotein Testing and Subfractionation Are Clinically Useful | journal = Circulation | volume = 119 | issue = 17 | date = 2009-05-05 | issn = 0009-7322 | doi = 10.1161/CIRCULATIONAHA.108.809582 | pages = 2383–2395| pmid = 19414656 }}</ref><ref>
{{cite web | date = 2020-03-20 | title = New Information on Accuracy of LDL-C Estimation | website = American College of Cardiology | url = https://www.acc.org/latest-in-cardiology/articles/2020/03/19/16/00/new-information-on-accuracy-of-ldl-c-estimation | access-date = 2024-03-16 | archiveurl = https://web.archive.org/web/20231206011034/https://www.acc.org/latest-in-cardiology/articles/2020/03/19/16/00/new-information-on-accuracy-of-ldl-c-estimation | archivedate = 2023-12-06 | url-status = live}}</ref><ref>
{{cite web | title = Friedewald equation for calculating VLDL and LDL - All About Cardiovascular System and Disorders | website = Johnson's Techworld - Reliving my hobbies | date = 2017-11-04 | url = https://johnsonfrancis.org/professional/friedewald-equation-for-calculating-vldl-and-ldl/ | access-date = 2024-03-16 | archiveurl = https://web.archive.org/web/20230928140358/https://johnsonfrancis.org/professional/friedewald-equation-for-calculating-vldl-and-ldl/ | archivedate = 2023-09-28 | url-status = live}}</ref>

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:

LDL <math>\approx</math> total cholesterol – HDL – (0.2 x fasting triglycerides).<ref>{{cite journal | vauthors = 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 | doi = 10.1093/clinchem/18.6.499 | doi-access = free }}</ref>

However, this equation is not valid on nonfasting blood samples or if fasting triglycerides are elevated (>4.5&nbsp;mmol/L or >~400&nbsp;mg/dL). Recent guidelines have, therefore, advocated the use of direct methods for the measurement of LDL wherever possible.<ref name = "ESC 2011"/> It may be useful to measure all lipoprotein subfractions ([[Very-low-density lipoprotein|VLDL]], [[Intermediate density lipoprotein|IDL]], [[low-density lipoprotein|LDL]], and 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"/>

===Classification===
{{main|Hyperlipidemia}}
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 between atherosclerosis progression and clinical consequences. If the hypercholesterolemia is hereditary (familial hypercholesterolemia), more often a [[Family history (medicine)|family history]] of premature, earlier onset atherosclerosis is found.<ref>{{cite book | vauthors = Ison HE, Clarke SL, Knowles JW | chapter = Familial Hypercholesterolemia|date=1993| chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK174884/| title = GeneReviews |place=Seattle (WA) |publisher=University of Washington, Seattle |pmid=24404629 |access-date=2021-01-04 | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE }}</ref>

==Screening method==
The [[U.S. Preventive Services Task Force]] in 2008 strongly recommended 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 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|access-date=2010-11-04|archive-url=https://web.archive.org/web/20150210081159/http://www.uspreventiveservicestaskforce.org/uspstf/uspschol.htm|archive-date=2015-02-10|url-status=dead}}</ref> In 2016 they concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.<ref>{{cite journal | vauthors = Chou R, Dana T, Blazina I, Daeges M, Bougatsos C, Jeanne TL | title = Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force | journal = Annals of Internal Medicine | volume = 165 | issue = 8 | pages = 560–564 | date = October 2016 | pmid = 27538032 | doi = 10.7326/M16-0946 | s2cid = 20592431 }}</ref><ref>{{cite journal | vauthors = Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, García FA, Gillman MW, Kemper AR, Krist AH, Kurth AE, Landefeld CS, LeFevre M, Mangione CM, Owens DK, Phillips WR, Phipps MG, Pignone MP, Siu AL | display-authors = 6 | title = Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 316 | issue = 6 | pages = 625–633 | date = August 2016 | pmid = 27532917 | doi = 10.1001/jama.2016.9852 | doi-access = free }}</ref>

In Canada, screening is recommended for men 40 and older and women 50 and older.<ref>{{cite journal | vauthors = Genest J, Frohlich J, Fodor G, McPherson R | title = Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update | journal = CMAJ | volume = 169 | issue = 9 | pages = 921–924 | date = October 2003 | pmid = 14581310 | pmc = 219626 }}</ref> In those with normal cholesterol levels, screening is recommended once every five years.<ref>{{cite journal | vauthors =  | 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 | volume = 106 | issue = 25 | pages = 3143–3421 | date = December 2002 | pmid = 12485966 | doi = 10.1161/circ.106.25.3143 | hdl-access = free | hdl = 2027/uc1.c095473168 }}</ref> Once people are on a statin further testing provides little benefit except possibly to determine compliance with treatment.<ref>{{cite journal | vauthors = Spector R, Snapinn SM | title = Statins for secondary prevention of cardiovascular disease: the right dose | journal = Pharmacology | volume = 87 | issue = 1–2 | pages = 63–69 | year = 2011 | pmid = 21228612 | doi = 10.1159/000322999 | doi-access = free }}</ref>

In the [[United Kingdom|UK]], after someone is diagnosed with familial hypercholesterolemia, clinicians, family, or both, contact first- and second-degree relatives to come forward for testing and treatment. Research suggests that clinician-only contact results in more people coming forward for testing.<ref>{{Cite journal |last1=Qureshi |first1=Nadeem |last2=Woods |first2=Bethan |last3=Neves de Faria |first3=Rita |last4=Saramago Goncalves |first4=Pedro |last5=Cox |first5=Edward |last6=Leonardi-Bee |first6=Jo |last7=Condon |first7=Laura |last8=Weng |first8=Stephen |last9=Akyea |first9=Ralph K. |last10=Iyen |first10=Barbara |last11=Roderick |first11=Paul |last12=Humphries |first12=Steve E. |last13=Rowlands |first13=William |last14=Watson |first14=Melanie |last15=Haralambos |first15=Kate |date=2023-10-24 |title=Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis |url=https://www.journalslibrary.nihr.ac.uk/hta/ctmd0148/ |journal=Health Technology Assessment |language=EN |volume=27 |issue=16 |pages=1–140 |doi=10.3310/CTMD0148 |issn=2046-4924 |pmc=10658348 |pmid=37924278}}</ref><ref>{{Cite journal |date=30 April 2024 |title=What is the best way to identify people with inherited high cholesterol? |url=https://evidence.nihr.ac.uk/alert/what-is-the-best-way-to-identify-people-with-familial-hypercholesterolaemia/ |journal=NIHR Evidence|doi=10.3310/nihrevidence_62958 }}</ref>

==Treatment==
Treatment recommendations have been based on four risk levels for heart disease.<ref name=Gru2004>{{cite journal | vauthors = Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ | display-authors = 6 | title = Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines | journal = Circulation | volume = 110 | issue = 2 | pages = 227–239 | date = July 2004 | pmid = 15249516 | doi = 10.1161/01.cir.0000133317.49796.0e | doi-access = free | url = https://cdr.lib.unc.edu/downloads/02870x84j }}</ref> For each risk level, LDL cholesterol levels representing goals and thresholds for treatment and other action are made.<ref name=Gru2004/> The higher the risk category, the lower the cholesterol thresholds.<ref name=Gru2004/>

{| class="wikitable" border:solid 1px #999999; margin:0 0 1em 1em;"
|+LDL cholesterol level thresholds<ref name=Gru2004/>
|-
! rowspan=2|Risk category
! colspan=3|Criteria for risk category
! colspan="2" |Consider lifestyle modifications
! colspan="2" |Consider medication
|-
!No. of risk factors†
!
!10-year risk of<br>[[myocardial ischemia]]
! mmol/litre
! mg/dL
! mmol/litre
! mg/dL
|-
| High
| Prior heart disease||OR
| >20%||>2.6<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 |journal = Best Buy Drugs |page = 9 |url = http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/StatinsUpdate-FINAL.pdf |access-date = 27 March 2013}}</ref>
| >100|| >2.6
| >100
|-
| Moderately high
|2 or more||AND
| 10–20%||>3.4
| >130||>3.4
| >130
|-
| Moderate
| 2 or more||AND
| <10%||>3.4
| >130||>4.1
| >160
|-
| Low
| colspan=3|0 or 1||>4.1
| >160||>4.9
| >190
|-
| colspan="8" |†Risk factors include cigarette smoking, hypertension (BP ≥140/90&nbsp;mm Hg or on antihypertensive medication),<br>low HDL cholesterol (<40&nbsp;mg/dL), family history of premature heart disease, and age (men ≥45 years; women ≥55 years).
|-
|}
For those at high risk, a combination of lifestyle modification and [[statins]] has been shown to decrease mortality.<ref name="BMJ2008"/>

===Lifestyle===
Lifestyle changes recommended for those with high cholesterol include: smoking cessation, limiting alcohol consumption, increasing physical activity, and maintaining a healthy weight.<ref name="ReferenceA"/>

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&nbsp;mg/dl.<ref name =Ito2011/>

===Diet===
Eating a diet with a high proportion of vegetables, fruit, dietary fiber, and low in fats results in a modest decrease in total cholesterol.<ref>{{cite journal | vauthors = Bhattarai N, Prevost AT, Wright AJ, Charlton J, Rudisill C, Gulliford MC | title = Effectiveness of interventions to promote healthy diet in primary care: systematic review and meta-analysis of randomised controlled trials | journal = BMC Public Health | volume = 13 | pages = 1203 | date = December 2013 | pmid = 24355095 | pmc = 3890643 | doi = 10.1186/1471-2458-13-1203 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hartley L, Igbinedion E, Holmes J, Flowers N, Thorogood M, Clarke A, Stranges S, Hooper L, Rees K | display-authors = 6 | title = Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 6 | pages = CD009874 | date = June 2013 | pmid = 23736950 | pmc = 4176664 | doi = 10.1002/14651858.CD009874.pub2 }}</ref><ref name =Ito2011/>

<!-- Cholesterol -->
Eating dietary cholesterol causes a small rise in serum cholesterol,<ref name="Brownawell 355–364">{{cite journal | vauthors = Brownawell AM, Falk MC | title = Cholesterol: where science and public health policy intersect | journal = Nutrition Reviews | volume = 68 | issue = 6 | pages = 355–364 | date = June 2010 | pmid = 20536780 | doi = 10.1111/j.1753-4887.2010.00294.x | doi-access = free }}</ref><ref name="Berger 276–294">{{cite journal | vauthors = Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ | title = Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis | journal = The American Journal of Clinical Nutrition | volume = 102 | issue = 2 | pages = 276–294 | date = August 2015 | pmid = 26109578 | doi = 10.3945/ajcn.114.100305 | doi-access = free }}</ref> the magnitude of which can be predicted using the [[Ancel Keys#Keys equation|Keys]]<ref name="Keys 776–787">{{cite journal | vauthors = Keys A, Anderson JT, Grande F | title = Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet | journal = Metabolism | volume = 14 | issue = 7 | pages = 776–787 | date = July 1965 | pmid = 25286466 | doi = 10.1016/0026-0495(65)90004-1 }}</ref> and [[D. Mark Hegsted#Hegsted equation|Hegsted]]<ref name="Hegsted 281–295">{{cite journal | vauthors = Hegsted DM, McGandy RB, Myers ML, Stare FJ | title = Quantitative effects of dietary fat on serum cholesterol in man | journal = The American Journal of Clinical Nutrition | volume = 17 | issue = 5 | pages = 281–295 | date = November 1965 | pmid = 5846902 | doi = 10.1093/ajcn/17.5.281 | doi-access = free }}</ref> equations. Dietary limits for cholesterol were proposed in the United States, but not in Canada, the United Kingdom, and Australia.<ref name="Brownawell 355–364"/> However, in 2015 the [[Dietary Guidelines Advisory Committee]] in the United States removed its recommendation of limiting cholesterol intake.<ref name=USDA2015>{{cite web |title=Scientific Report of the 2015 Dietary Guidelines Advisory Committee|url=http://health.gov/dietaryguidelines/2015-scientific-report/pdfs/scientific-report-of-the-2015-dietary-guidelines-advisory-committee.pdf|website=health.gov|access-date=16 May 2016|page=17|date=2015|quote=The 2015 DGAC will not bring forward this recommendation 644 because available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol, consistent with the conclusions of the AHA/ACC report.}}</ref>

<!-- Fats -->
A 2020 Cochrane review found replacing [[saturated fat]] with [[polyunsaturated fat]] resulted in a small decrease in [[cardiovascular disease]] by decreasing blood cholesterol.<ref>{{cite journal | vauthors = Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS | title = Reduction in saturated fat intake for cardiovascular disease | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 8 | pages = CD011737 | date = August 2020 | pmid = 32827219 | pmc = 8092457 | doi = 10.1002/14651858.CD011737.pub3 }}</ref> Other reviews have not found an effect from saturated fats on cardiovascular disease.<ref>{{cite journal | vauthors = Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E | display-authors = 6 | title = Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 160 | issue = 6 | pages = 398–406 | date = March 2014 | pmid = 24723079 | doi = 10.7326/M13-1788 }}</ref><ref name=BMJ2015>{{cite journal | vauthors = de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J, Anand SS | display-authors = 6 | title = Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies | journal = BMJ | volume = 351 | pages = h3978 | date = August 2015 | pmid = 26268692 | pmc = 4532752 | doi = 10.1136/bmj.h3978 }}</ref> [[Trans fats]] are recognized as a potential risk factor for cholesterol-related cardiovascular disease, and avoiding them in an adult diet is recommended.<ref name=BMJ2015/>

The [[National Lipid Association]] recommends that people with familial hypercholesterolemia restrict intakes of total fat to 25–35% of energy intake, saturated fat to less than 7% of energy intake, and cholesterol to less than 200&nbsp;mg per day.<ref name =Ito2011/> Changes in total fat intake in low-calorie diets do not appear to affect blood cholesterol.<ref>{{cite journal | vauthors = Schwingshackl L, Hoffmann G | title = Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and meta-analysis | journal = Journal of the Academy of Nutrition and Dietetics | volume = 113 | issue = 12 | pages = 1640–1661 | date = December 2013 | pmid = 24139973 | doi = 10.1016/j.jand.2013.07.010 | quote = Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. }}</ref>

<!-- Fiber and carbs -->
Increasing soluble fiber consumption has been shown to reduce levels of LDL cholesterol, with each additional gram of soluble fiber reducing LDL by an average of 2.2&nbsp;mg/dL (0.057&nbsp;mmol/L).<ref>{{cite journal | vauthors = Brown L, Rosner B, Willett WW, Sacks FM | title = Cholesterol-lowering effects of dietary fiber: a meta-analysis | journal = The American Journal of Clinical Nutrition | volume = 69 | issue = 1 | pages = 30–42 | date = January 1999 | pmid = 9925120 | doi = 10.1093/ajcn/69.1.30 | doi-access = free }}</ref> Increasing consumption of whole grains also reduces LDL cholesterol, with whole grain oats being particularly effective.<ref>{{cite journal | vauthors = Hollænder PL, Ross AB, Kristensen M | title = Whole-grain and blood lipid changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies | journal = The American Journal of Clinical Nutrition | volume = 102 | issue = 3 | pages = 556–572 | date = September 2015 | pmid = 26269373 | doi = 10.3945/ajcn.115.109165 | doi-access = free }}</ref> Inclusion of 2 g per day of [[phytosterols]] and phytostanols and 10 to 20 g per day of soluble fiber decreases dietary cholesterol absorption.<ref name =Ito2011/> A diet high in [[fructose]] can raise LDL cholesterol levels in the blood.<ref>{{cite journal | vauthors = Schaefer EJ, Gleason JA, Dansinger ML | title = Dietary fructose and glucose differentially affect lipid and glucose homeostasis | journal = The Journal of Nutrition | volume = 139 | issue = 6 | pages = 1257S–1262S | date = June 2009 | pmid = 19403705 | pmc = 2682989 | doi = 10.3945/jn.108.098186 }}</ref>

===Medication===
Statins are the typically used medications, in addition to healthy lifestyle interventions.<ref>{{cite journal | vauthors = Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Sperling L, Virani SS, Yeboah J | display-authors = 6 | title = 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 139 | issue = 25 | pages = e1082–e1143 | date = June 2019 | pmid = 30586774 | pmc = 7403606 | doi = 10.1161/CIR.0000000000000625 }}</ref> Statins can reduce total cholesterol by about 50% in the majority of people,<ref name="ESC 2011" /> and are effective in reducing the risk of cardiovascular disease in both people with<ref>{{cite journal | vauthors = Koskinas KC, Siontis GC, Piccolo R, Mavridis D, Räber L, Mach F, Windecker S | title = Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials | journal = European Heart Journal | volume = 39 | issue = 14 | pages = 1172–1180 | date = April 2018 | pmid = 29069377 | doi = 10.1093/eurheartj/ehx566 | doi-access = free }}</ref> and without pre-existing cardiovascular disease.<ref name="CMAJ11">{{cite journal | vauthors = Tonelli M, Lloyd A, Clement F, Conly J, Husereau D, Hemmelgarn B, Klarenbach S, McAlister FA, Wiebe N, Manns B | display-authors = 6 | title = Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis | journal = CMAJ | volume = 183 | issue = 16 | pages = E1189–E1202 | date = November 2011 | pmid = 21989464 | pmc = 3216447 | doi = 10.1503/cmaj.101280 }}</ref><ref>{{cite journal | vauthors = Mills EJ, Wu P, Chong G, Ghement I, Singh S, Akl EA, Eyawo O, Guyatt G, Berwanger O, Briel M | display-authors = 6 | title = Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials | journal = QJM | volume = 104 | issue = 2 | pages = 109–124 | date = February 2011 | pmid = 20934984 | doi = 10.1093/qjmed/hcq165 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C | display-authors = 6 | 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 | volume = 380 | issue = 9841 | pages = 581–590 | date = August 2012 | pmid = 22607822 | pmc = 3437972 | doi = 10.1016/S0140-6736(12)60367-5 | collaboration = Cholesterol Treatment Trialists' Collaborators }}</ref><ref>{{cite journal | vauthors = Chou R, Dana T, Blazina I, Daeges M, Jeanne TL | title = Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force | journal = JAMA | volume = 316 | issue = 19 | pages = 2008–2024 | date = November 2016 | pmid = 27838722 | doi = 10.1001/jama.2015.15629 | doi-access = free }}</ref> In people without cardiovascular disease, statins have been shown to reduce all-cause mortality, fatal and non-fatal coronary heart disease, and strokes.<ref name=Tay2013>{{cite journal | vauthors = Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S | display-authors = 6 | title = Statins for the primary prevention of cardiovascular disease | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 1 | pages = CD004816 | date = January 2013 | pmid = 23440795 | pmc = 6481400 | doi = 10.1002/14651858.cd004816.pub5 }}</ref> Greater benefit is observed with the use of high-intensity statin therapy.<ref>{{cite journal | vauthors = Pisaniello AD, Scherer DJ, Kataoka Y, Nicholls SJ | title = Ongoing challenges for pharmacotherapy for dyslipidemia | journal = Expert Opinion on Pharmacotherapy | volume = 16 | issue = 3 | pages = 347–356 | date = February 2015 | pmid = 25476544 | doi = 10.1517/14656566.2014.986094 | s2cid = 539314 }}</ref> Statins may improve [[quality of life]] when used in people without existing cardiovascular disease (i.e. for primary prevention).<ref name=Tay2013/> Statins decrease cholesterol in children with hypercholesterolemia, but no studies as of 2010 show improved outcomes<ref name="Leben2010">{{cite journal | vauthors = 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 = Archives of Disease in Childhood | volume = 95 | issue = 9 | pages = 673–680 | date = September 2010 | pmid = 20515970 | doi = 10.1136/adc.2008.157024 | s2cid = 24263653 }}</ref> and diet is the mainstay of therapy in childhood.<ref name="ESC 2011" />

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 or in pregnant women.<ref name="NICE67" /> Injectable antibodies against the protein PCSK9 ([[evolocumab]], [[bococizumab]], [[alirocumab]]) can reduce LDL cholesterol and have been shown to reduce mortality.<ref name="Navarese2015">{{cite journal | vauthors = Navarese EP, Kolodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, Brockmeyer M, Kandzari DE, Kubica JM, D'Agostino RB, Kubica J, Volpe M, Agewall S, Kereiakes DJ, Kelm M | display-authors = 6 | title = Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis | journal = Annals of Internal Medicine | volume = 163 | issue = 1 | pages = 40–51 | date = July 2015 | pmid = 25915661 | doi = 10.7326/M14-2957 | s2cid = 207538324 }}</ref>

===Guidelines===

In the US, guidelines exist from the [[National Cholesterol Education Program]] (2004)<ref name=pmid15358046>{{cite journal | vauthors = Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ | display-authors = 6 | title = Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines | journal = Journal of the American College of Cardiology | volume = 44 | issue = 3 | pages = 720–732 | date = August 2004 | pmid = 15358046 | doi = 10.1016/j.jacc.2004.07.001 | s2cid = 54525085 | doi-access = free | url = https://cdr.lib.unc.edu/downloads/02870x84j }}</ref> and a joint body of professional societies led by the [[American Heart Association]].<ref>{{cite journal | vauthors = Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Sperling L, Virani SS, Yeboah J | display-authors = 6 | title = 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 139 | issue = 25 | pages = e1046–e1081 | date = June 2019 | pmid = 30565953 | doi = 10.1161/CIR.0000000000000624 | doi-access = free }}</ref>

In the UK, the [[National Institute for Health and Clinical Excellence]] has made recommendations for the treatment of elevated cholesterol levels, published in 2008,<ref name=NICE67/> and a new guideline appeared in 2014 that covers the prevention of cardiovascular disease in general.<ref>{{cite web |last1=National Institute for Health and Clinical Excellence |title=Cardiovascular disease: risk assessment and reduction, including lipid modification |url=https://www.nice.org.uk/guidance/cg181 |website=NICE |date=18 July 2014 |access-date=27 May 2019}}</ref>

The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology and the European Atherosclerosis Society published guidelines for the management of dyslipidaemias in 2011.<ref name ="ESC 2011"/>

===Specific populations===
Among people whose [[life expectancy]] is relatively short, hypercholesterolemia is not a risk factor for death by any cause including coronary heart disease.<ref name="AMDAten">{{Citation |author1 = AMDA – The Society for Post-Acute and Long-Term Care Medicine |author1-link = AMDA – The Society for Post-Acute and Long-Term  Care Medicine |date = February 2014 |title = Ten Things Physicians and Patients Should Question |publisher = AMDA – The Society for Post-Acute and Long-Term Care Medicine |work = [[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url = http://www.choosingwisely.org/doctor-patient-lists/amda/ |access-date = 20 April 2015}}</ref> Among people older than 70, hypercholesterolemia is not a risk factor for being hospitalized with [[myocardial infarction]] or [[angina]].<ref name="AMDAten"/> There are also increased risks in people older than 85 in the use of [[statin]] drugs.<ref name="AMDAten"/> Because of this, medications that lower lipid levels should not be routinely used among people with limited life expectancy.<ref name="AMDAten"/>

The [[American College of Physicians]] recommends the following for hypercholesterolemia in people with [[diabetes]]:<ref name=pmid15096336>{{cite journal | vauthors = Snow V, Aronson MD, Hornbake ER, Mottur-Pilson C, Weiss KB | title = Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians | journal = Annals of Internal Medicine | volume = 140 | issue = 8 | pages = 644–649 | date = April 2004 | pmid = 15096336 | doi = 10.7326/0003-4819-140-8-200404200-00012 | s2cid = 6744974 }}</ref>
# [[lipid-lowering agent|Lipid-lowering therapy]] should be used for secondary prevention of cardiovascular mortality and morbidity for all adults with known coronary artery disease and type 2 diabetes.
# Statins should be used for primary prevention against macrovascular (coronary artery disease, cerebrovascular disease, or peripheral vascular disease) complications in adults with type 2 diabetes and other cardiovascular risk factors.
# Once lipid-lowering therapy is initiated, people with type 2 diabetes mellitus should be taking at least moderate doses of a statin.<ref name=pmid15096337>{{cite journal | vauthors = Vijan S, Hayward RA | title = Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians | journal = Annals of Internal Medicine | volume = 140 | issue = 8 | pages = 650–658 | date = April 2004 | pmid = 15096337 | doi = 10.7326/0003-4819-140-8-200404200-00013 | s2cid = 25448635 | doi-access =  }}</ref>
# For those people with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

===Alternative medicine===
A 2002 survey found that 1.1% of U.S. adults who used [[alternative medicine]] did so to treat high cholesterol.
Consistent with previous surveys, this one found the majority of individuals (55%) used it in conjunction with [[conventional medicine]].<ref name=NCCIH>{{cite journal | vauthors = Barnes PM, Powell-Griner E, McFann K, Nahin RL | title = Complementary and alternative medicine use among adults: United States, 2002 | journal = Advance Data | volume = 343 | issue = 343 | pages = 1–19 | date = May 2004 | pmid = 15188733 | url = https://pubmed.ncbi.nlm.nih.gov/15188733/ }}</ref> A systematic review<ref>{{cite journal | vauthors = Liu ZL, Liu JP, Zhang AL, Wu Q, Ruan Y, Lewith G, Visconte D | title = Chinese herbal medicines for hypercholesterolemia | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD008305 | date = July 2011 | pmid = 21735427 | pmc = 3402023 | doi = 10.1002/14651858.CD008305.pub2 | collaboration = Cochrane Metabolic and Endocrine Disorders Group }}</ref> of the effectiveness of [[herbal medicine]]s used in [[traditional Chinese medicine]] had inconclusive results due to the poor methodological quality of the included studies.
A review of trials of phytosterols and/or phytostanols, average dose 2.15 g/day, reported an average of 9% lowering of LDL-cholesterol.<ref name=PMID1909>{{cite journal | vauthors = Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, Geleijnse JM, Trautwein EA | display-authors = 6 | title = Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake | journal = The Journal of Nutrition | volume = 139 | issue = 2 | pages = 271–284 | date = February 2009 | pmid = 19091798 | doi = 10.3945/jn.108.095125 | doi-access = free }}</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&nbsp;g/day of phytosterols or phytostanols. Some researchers, however, are concerned about diet supplementation with plant sterol esters and draw attention to the lack of long-term safety data.<ref name=Wein2009>{{cite journal | vauthors = Weingärtner O, Böhm M, Laufs U | title = Controversial role of plant sterol esters in the management of hypercholesterolaemia | journal = European Heart Journal | volume = 30 | issue = 4 | pages = 404–409 | date = February 2009 | pmid = 19158117 | pmc = 2642922 | doi = 10.1093/eurheartj/ehn580 }}</ref>

==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=https://www.cdc.gov/nchs/data/databriefs/db92.pdf|publisher=CDC|date=April 2012}}</ref>

Average total cholesterol in the United Kingdom is 5.9&nbsp;mmol/L, while in rural China and Japan, average total cholesterol is 4&nbsp;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"/>

==Research directions==
[[Gene therapy]] is being studied as a potential treatment.<ref>{{cite journal | vauthors = Van Craeyveld E, Jacobs F, Gordts SC, De Geest B | title = Gene therapy for familial hypercholesterolemia | journal = Current Pharmaceutical Design | volume = 17 | issue = 24 | pages = 2575–2591 | year = 2011 | pmid = 21774774 | doi = 10.2174/138161211797247550 }}</ref><ref>{{cite journal | vauthors = Al-Allaf FA, Coutelle C, Waddington SN, David AL, Harbottle R, Themis M | title = LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives | journal = International Archives of Medicine | volume = 3 | pages = 36 | date = December 2010 | pmid = 21144047 | pmc = 3016243 | doi = 10.1186/1755-7682-3-36 | doi-access = free }}</ref>

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|   DiseasesDB     = 6226
|   ICD10          = {{ICD10|E|78|0|e|70}}
|   ICD9           = {{ICD9|272.0}}
|   OMIM           =
|   MedlinePlus    = 000403
|   ICDO           =
|   eMedicineSubj  = med
|   eMedicineTopic = 1073
|   MeshID         = D006937
}}

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[[Category:Cholesterol and steroid metabolism disorders]]
[[Category:Lipid metabolism disorders]]
[[Category:Medical conditions related to obesity]]