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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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| {{DiseaseDisorder infobox |
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| Name = Hypercholesterolemia |
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| Caption = [[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 = |
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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}}
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| {{CMG}}
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| '''Associate Editors-In-Chief:''' 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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| ==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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| ==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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| ==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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| * [[Kidney]] disease ([[nephrotic syndrome]])
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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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| ==Treatment==
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| [http://clinicalevidence.com Clinical Evidence] has summarized treatment for both primary prevention <ref name="pmid16620402">{{cite journal |author=Pignone M |title=Primary prevention: dyslipidaemia |journal=Clin Evid |volume= |issue= |pages=142-50 |year= |pmid=16620402 | url=http://clinicalevidence.com/ceweb/conditions/cvd/0215/0215.jsp}}</ref> and secondary prevention <ref name="pmid16973010">{{cite journal |author=Gami A |title=Secondary prevention of ischaemic cardiac events |journal=Clin Evid |volume= |issue= |pages=195-228 |year= |pmid=16973010 | url=http://clinicalevidence.com/ceweb/conditions/cvd/0206/0206_guidelines.jsp}}</ref>. Two factors to consider when choosing therapy are the patient's risk of coronary disease and their lipoprotein pattern.
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| :'''Risk of coronary disease'''. To calculated the benefit of treatment, there are two online calculators that can estimate baseline risk <ref name="webMedDecisions">{{cite web |url=http://www.med-decisions.com/ |title=med-decisions.com |accessdate= |accessmonthday=Feb 26 |accessdaymonth = |accessyear=2007 |author= Pignone MP |last= |first= |authorlink= |coauthors= Sheridan SL |date= |year= |month= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote= }}</ref> <ref name="webNCEP">{{cite web |url=http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof |title=10-year CVD Risk Calculator (Risk Assessment Tool for Estimating 10-year Risk of Developing Hard CHD (Myocardial Infarction and Coronary Death) Version) |accessdate= |accessmonthday=Feb 26 |accessdaymonth = |accessyear=2007 |author= National Cholesterol Education Program |last= |first= |authorlink= |coauthors= |date= |year= |month= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote= }}</ref>. Combining the baseline risk with the [[relative risk reduction]] of a treatment can lead to the absolute risk reduction of [[number needed to treat]]. For example, one of the calculators projects that a patient had a 10% risk of coronary disease over ten years. As noted below, the [[relative risk reduction]] of a [[statin]] is 30%. Thus, after 4-7 years of treatment with a [[statin]], a patient's risk will drop to 7%. This equates to an absolute risk reduction of 3%, or a [[number needed to treat]] of 33. Thirty three such patients must be treated for 4-7 years for one to benefit.
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| :'''Lipoprotein patterns'''. (''See [[hyperlipoproteinemia]] for details'') The treatment depends on the type of hypercholesterolemia. Clinical trials, starting in the 1970s, have repeatedly and increasingly found that ''normal'' [[cholesterol]] values do not necessarily reflect healthy [[cholesterol]] values. This has increasingly lead to the newer concept of [[dyslipidemia]], despite normo-cholesterolemia. Thus there has been increasing recognition of the importance of "lipoprotein subclass analysis" as an important approach to better understand and change the connection between cholesterol transport and [[atherosclerosis]] progression. [[Fredrickson classification#Classification|Fredrickson Types]] IIa and IIb can be treated with [[Dieting|diet]], [[statin]]s (most prominently [[rosuvastatin]], [[atorvastatin]], [[simvastatin]], or [[pravastatin]]), cholesterol absorption inhibitors ([[ezetimibe]]), [[fibrate]]s ([[gemfibrozil]], [[bezafibrate]], [[fenofibrate]] or [[ciprofibrate]]), vitamin B3 ([[niacin]]), [[bile acid sequestrant]]s ([[colestipol]], [[cholestyramine]]), [[LDL apheresis]] and in hereditary severe cases [[liver transplantation]].
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| Multiple clinical trials, each, by design, examining only one of multiple relevant issues, have increasingly examined the connection between these issues and [[atherosclerosis]] clinical consequences. Some of the better recent randomized human outcome trials include [[ASTEROID trial|ASTEROID]], ASCOT-LLA, REVERSAL, PROVE-IT, CARDS, [[Heart Protection Study]], HOPE, PROGRESS, COPERNICUS, and especially a newer research approach utilizing a synthetically produced and IV administered human [[High density lipoprotein|HDL]], the Apo A-I Milano Trial.
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| ===Diet===
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| On the other hand, and though less dramatic than the many cardiovascular procedures, some people, especially with newer and more sophisticated information, are changing their eating and especially food supplement patterns, many of the supplements still being prescription agents. Though generally not aware of the internal changes in their [[cholesterol]] transport patterns, recent trials have demonstrated increasing success with some of these strategies; see the [[Low density lipoprotein|LDL]], [[High density lipoprotein|HDL]] and [[IVUS]] sections.
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| Dietary changes can potentially be very strong.<ref name="pmid1944471">{{cite journal |author=McMurry MP, Cerqueira MT, Connor SL, Connor WE |title=Changes in lipid and lipoprotein levels and body weight in Tarahumara Indians after consumption of an affluent diet |journal=N. Engl. J. Med. |volume=325 |issue=24 |pages=1704-8 |year=1991 |pmid=1944471 |doi=|url=http://content.nejm.org/cgi/content/abstract/325/24/1704}}</ref>
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| ===Medications===
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| Many primary physicians and heart specialists will initially prescribe medication in combination with diet and exercise. According to various resources, [[statins]] are the most commonly used and effective forms of medication for the treatment of high cholesterol. The [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)] estimated that after 5 to 7 years of treatment, the [[relative risk reduction]] by [[statins]] on coronary heart disease events is decreased by approximately 30% <ref name="pmid11306236">.</ref> <ref name="webPignone">.</ref>. More recently, a [[meta-analysis]] reported an almost identical [[relative risk reduction]] of 29.2% in low risk patients treated for 4.3 years <ref name="pmid17130382">{{cite journal |author=Thavendiranathan P, Bagai A, Brookhart M, Choudhry N |title=Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials |journal=Arch Intern Med |volume=166 |issue=21 |pages=2307-13 |year=2006 |pmid=17130382}}</ref>. A [[relative risk reduction]] of 19% in coronary mortality was found in a [[meta-analysis]] of patients at all levels of risk.<ref name="pmid16214597">{{cite journal |author=Baigent C, Keech A, Kearney PM, ''et al'' |title=Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins |journal=Lancet |volume=366 |issue=9493 |pages=1267-78 |year=2005 |pmid=16214597 |doi=10.1016/S0140-6736(05)67394-1}}</ref>
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| ===Clinical practice 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 |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>. Their recommendations are:
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| * Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
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| * Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
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| * Recommendation 3: Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d; pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another statin")<ref name="pmid15096337">{{cite journal |author=Vijan S, Hayward RA |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 |doi=|url=http://www.annals.org/cgi/content/full/140/8/650}}</ref>.
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| * Recommendation 4: For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.
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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}}</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>
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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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| {{SIB}}
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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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