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| '''For patient information on hypercholesterolemia click [[Hypercholesterolemia (patient information)|here]]'''
| | #REDIRECT[[Hyperlipoproteinemia]] |
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| '''For patient information on coronary risk profile click [[Coronary risk profile (patient information)|here]]'''
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| {{Hypercholesterolemia}}
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| {{CMG}}; {{AE}} Smit Shrivastava, M.D. [mailto:dr.smit.shrivastava@gmail.com] and Bhaskar Purushottam, M.D. [mailto:bpurushottam@gmail.com]
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| Keywords and synonyms: cholesterol guidelines, NCEP guidelines, ATP guidelines, high cholesterol, hyperlipidemia
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| ==[[Hypercholesterolemia overview|Overview]]==
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| '''Hypercholesterolemia''' (literally: high blood cholesterol) is the presence of high levels of [[cholesterol]] in the blood.<ref name="pmid12957096">{{cite journal |author=Durrington P |title=Dyslipidaemia |journal=Lancet |volume=362 |issue=9385 |pages=717-31 |year=2003 |pmid=12957096}}</ref> It is not a [[disease]] but a [[metabolism|metabolic]] derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably [[cardiovascular disease]]. It is closely related to the terms "[[hyperlipidemia]]" (elevated levels of [[lipids]]) and "[[hyperlipoproteinemia]]" (elevated levels of [[lipoproteins]]). [[Familial hypercholesterolemia]] is a rare [[genetic disorder]] that can occur in families, where sufferers cannot properly metabolize cholesterol.
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| ==Diagnosis==
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| [[Hypercholesterolemia history and symptoms|History and symptoms]] | [[Hypercholesterolemia physical examination|Physical examination]]
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| ==[[Hypercholesterolemia differential diagnosis|Differential Diagnosis of Disorders Associated with Hypercholesterolemia]]==
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| When measuring [[cholesterol]], it is important to measure its subfractions before drawing a conclusion on the cause of the problem. The subfractions are [[Low density lipoprotein|LDL]], [[High density lipoprotein|HDL]] and [[Very low density lipoprotein|VLDL]]. In the past, LDL and VLDL levels were rarely measured directly due to cost concerns. VLDL levels are reflected in the levels of [[triglyceride]]s (generally about 45% of triglycerides is composed of VLDL). LDL was usually estimated as a calculated value from the other fractions (total cholesterol minus HDL and VLDL); this method is called the ''Friedewald'' calculation; specifically: LDL ~= Total Cholesterol - HDL - (0.2 x Triglycerides).
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| Less expensive (and less accurate) laboratory methods and the ''Friedewald'' calculation have long been utilized because of the complexity, labor and expense of the [[electrophoresis|electrophoretic]] methods developed in the 1970s to identify the different [[lipoprotein]] particles which transport cholesterol in the blood. As of 1980, the original methods, developed by research work in the mid-1970s cost about $5K, US 1980 dollars, per blood sample/person.
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| With time, more advanced laboratory analyses have been developed which do measure LDL and VLDL particle sizes and levels, and at far lower cost. These have partly been developed and become more popular as a result of the increasing clinical trial evidence that intentionally changing cholesterol transport patterns, including to certain ''abnormal'' values compared to most adults, often has a dramatic effect on reducing, even partially reversing, the [[atherosclerosis|atherosclerotic]] process. With ongoing research and advances in laboratory methods, the prices for more sophisticated analyses have markedly decreased, to less than $100, US 2004, by some labs, and with simultaneous increases in the accuracy of measurement for some of the methods.
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| ===Drug Side Effects===
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| *[[Basiliximab]]
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| *[[Elvitegravir]]
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| *[[Pegaspargase]]
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| *[[Sargramostim]]
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| ==Screening==
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| [[Screening (medicine) | Screening]] for a disease refers to testing for a disease, such as hypercholesterolemia, in patients who have no signs or symptoms of the disease.
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| In patients without any other risk factors, moderate hypercholesterolemia is often not treated. According to [[Framingham Heart Study]], people with an age greater than 50 years have no increased overall mortality with either high or low serum cholesterol levels. There is, however, a correlation between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels). This, however, does not mean that a decrease in serum levels is dangerous, as there has not yet been a recorded heart attack in the study in a person with a total cholesterol below 150 mg/dL.
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| The [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)] has evaluated screening for hypercholesterolemia <ref name="pmid11306236">{{cite journal |author=Pignone M, Phillips C, Atkins D, Teutsch S, Mulrow C, Lohr K |title=Screening and treating adults for lipid disorders |journal=Am J Prev Med |volume=20 |issue=3 Suppl |pages=77-89 |year=2001 |pmid=11306236 | doi=10.1016/S0749-3797(01)00255-0}}</ref> <ref name="webPignone">{{cite web |url=http://www.ahrq.gov/clinic/ajpmsuppl/lipidrr.htm |title=Screening for Lipid Disorders: Recommendations and Rationale |accessdate= |accessmonthday=Feb 26 |accessdaymonth = |accessyear=2007 |author=U.S. Preventive Services Task Force |last= |first= |authorlink= |coauthors= |date= |year= |month= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote= }}</ref>.
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| Regarding when to repeat evaluation of risk, "Repeat risk estimation before 8-10 years is not warranted for most people initially not requiring treatment. However, remeasurement within a year seems warranted in those with an initial 15-<20% risk [of cardiovascular disease within ten years]".<ref name="pmid23553971">{{cite journal| author=Bell KJ, Hayen A, Irwig L, Takahashi O, Ohde S, Glasziou P| title=When to remeasure cardiovascular risk in untreated people at low and intermediate risk: observational study. | journal=BMJ | year= 2013 | volume= 346 | issue= | pages= f1895 | pmid=23553971 | doi=10.1136/bmj.f1895 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23553971 }} </ref>
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| ==Classification==
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| ''See also [[hyperlipoproteinemia]] for biochemical details''
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| ===Fredrickson classification===
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| Classically, hypercholesterolemia was categorized by [[lipoprotein]] [[electrophoresis]] and the [[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]], as well as familial occurrence of the signs mentioned above.
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| ===Secondary causes===
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| There are a number of secondary causes for high cholesterol:
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| * [[Diabetes mellitus]] and [[metabolic syndrome]]
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| * [[Drugs]]- [[Desogestrel and Ethinyl Estradiol]], [[Letrozole]], [[Ritonavir]], [[Ruxolitinib]], [[Tretinoin]]
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| * [[nephrotic syndrome|Kidney disease]]
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| * [[Hypothyroidism]]
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| * [[Anorexia nervosa]]
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| * [[Zieve's syndrome]]
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| * [[Family history]]
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| * Diet: Saturated fat raises blood cholesterol levels. Although dietary cholesterol exerts some influence, the regulatory mechanism of the liver upon absorption of cholesterol decreases the effect of dietary cholesterol on total cholesterol levels. Thus it is mainly by limiting the amount of saturated fat in one's diet that helps lower total serum cholesterol.
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| *[[Weight]]. Being overweight is a definite risk factor for heart disease. It also tends to increase your cholesterol. Losing weight can help lower your LDL and total cholesterol levels, as well as raise your HDL and lower your triglyceride levels.
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| *Physical Activity. Lack of physical activity is a risk factor for heart disease. Regular physical activity can also help lower LDL (bad) cholesterol and raise HDL (good) cholesterol levels. It also helps you lose weight.
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| All three of these activities done together can have a positive effect on one's blood cholesterol level.
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| ==Dietary influence==
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| While part of the circulating cholesterol originates from diet, and restricting cholesterol intake may reduce blood cholesterol levels, there are various other links between the dietary pattern and cholesterol levels. The American Heart Association also compiles a list of the acceptable/unacceptable foods for those who are diagnosed with hypercholesterolemia.
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| ===Carbohydrates===
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| Evidence is accumulating that eating more [[carbohydrate]]s - especially simpler, more refined carbohydrates - increases levels of [[triglycerides]] in the blood, lowers HDL, and may shift the LDL particle distribution pattern into unhealthy [[atheroma|atherogenic]] patterns. Thus a low fat diet, which often means a higher carbohydrate intake, may actually be an unhealthy change.
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| ===Trans fats===
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| An increasing number of researchers are suggesting that a major dietary risk factor for cardiovascular diseases is [[trans fat|trans fatty acids]], and in the US the FDA has revised food labeling requirements to include listing trans fat quantities.
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| ==[[Hypercholesterolemia treatment|Treatment]]==
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| The primary target for hypercholesterolemia according to the latest NCEP ATP III guidelines is [[LDL]] cholesterol. A target LDL goal is established and treatment options are considered based on that.
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| Available classes of medications include the following list; however, it is not clear that any medications other than [[statin]]s improve clinical outcomes:<ref name="pmid25038074">{{cite journal| author=Keene D, Price C, Shun-Shin MJ, Francis DP| title=Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117 411 patients. | journal=BMJ | year= 2014 | volume= 349 | issue= | pages= g4379 | pmid=25038074 | doi=10.1136/bmj.g4379 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25038074 }} </ref>
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| * Hydroxymethylglutaryl-coenzyme A reductase inhibitors ([[statin]]s)
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| * [[Cholesteryl ester transfer protein]] (CETP) inhibitors ([[anacetrapib]], [[dalcetrapib]], [[evacetrapib]], [[torcetrapib]])
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| * Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 ([[alirocumab]])
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| * [[Clofibric acid]] derivatives
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| ===Clinical practice guidelines===
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| The [[Hypercholesterolemia NCEP ATP III guidelines|NCEP]] 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}}</ref>; however, their 2004 revisions have been criticized for use of nonrandomized, observational data.<ref name="pmid17015870">{{cite journal |author=Hayward RA, Hofer TP, Vijan 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 |doi=}}</ref>Various other 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 |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}}</ref>. However, most of the management for treatment of high blood cholesterol is based on [[NCEP]] guidelines.
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| ===Alternative medicine===
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| A [http://nccam.nih.gov/news/2004/052704.htm survey released in May 2004] by the [[National Center for Complementary and Alternative Medicine]] focused on who used [[alternative medicine|complementary and alternative medicine]] (CAM), what was used, and why it was used in the United States by adults age 18 years and over during 2002. According to this survey, CAM was used to treat cholesterol by 1.1% of U.S. adults who used CAM during 2002 ([http://nccam.nih.gov/news/report.pdf] table 3 on page 9). Consistent with previous studies, this study found that the majority of individuals (i.e., 54.9%) used CAM in conjunction with [[conventional medicine]] (page 6).
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| ==References==
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| <references/>
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| ==See also==
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| *[[Familial hypercholesterolemia]]
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| ==External links==
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| * [http://www.westonaprice.org/moderndiseases/benefits_cholest.html Alternative hypothesis about high cholesterol's role in health]
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| {{Metabolic pathology}}
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| [[de:Hypercholesterinämie]]
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| [[fr:Hypercholestérolémie]]
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| [[it:Ipercolesterolemia]]
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| [[nl:Hypercholesterolemie]]
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| [[ja:高脂血症]]
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| [[pl:Hipercholesterolemia]]
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| [[pt:Hipercolesterolemia]]
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| [[simple:Hypercholesterolemia]]
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| [[Category:Cardiology]]
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| [[Category:Lipid disorders]]
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| [[Category:Health risks]]
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| [[Category:Medical conditions related to obesity]]
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| [[Category:Inborn errors of metabolism]]
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| [[Category:Mature chapter]]
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