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==Historical Perspective== | ==Historical Perspective== | ||
From the early 1950s onward, Fredrickson specialized in the study of plasma [[lipoprotein]]s, compounds of [[protein]]s and [[lipid]]s which transport lipids in the blood. However, the study of [[lipid]]s in the blood has started early in the 1900's. In 1949, Faraday Society in Birmingham organized the first symposium on [[lipoprotein]]s and separated for the first time lipoproteins into alpha and beta types. In 1950, LDL was first isolated.<ref name="dx.doi.org">{{Cite web | last = | first = | title = http://dx.doi.org/10.1021/ja01157a121 | url = http://dx.doi.org/10.1021/ja01157a121 | publisher = | date = | accessdate = 8 November 2013 }}</ref> In 1973, Myant first hypothesized the role of LDL in the metabolism of [[cholesterol]].<ref name="pmid4354844">{{cite journal| author=Myant NB| title=Cholesterol metabolism. | journal=J Clin Pathol Suppl (Assoc Clin Pathol) | year= 1973 | volume= 5 | issue= | pages= 1-4 | pmid=4354844 | doi= | pmc=PMC1436101 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4354844 }} </ref> | |||
==Classification== | ==Classification== | ||
Prior approaches to the management of LDL aimed towards the classification of LDL concentrations and the treatment of subjects with [[dyslipidemia]] to a target LDL concentration. In 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III classified LDL concentrations into optimal, near optimal, borderline high, high, and very high.<ref name="pmid11368702">{{cite journal| author=Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults| title=Executive Summary of The 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). | journal=JAMA | year= 2001 | volume= 285 | issue= 19 | pages= 2486-97 | pmid=11368702 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11368702 }} </ref> However, the latest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults no longer takes into consideration LDL cut-off concentration but rather identifies groups of patients among whom the benefit of statin outweighs the risk of adverse events.<ref name="pmid24239923">{{cite journal| author=Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH et al.| title=2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2014 | volume= 63 | issue= 25 Pt B | pages= 2889-934 | pmid=24239923 | doi=10.1016/j.jacc.2013.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24239923 }} </ref> | |||
==Physiology== | ==Physiology== | ||
Low-density lipoprotein (LDL) belongs to the [[lipoprotein]] particle family. Its size is approximately 22 nm but since LDL particles contain a changing number of fatty acids they actually have a mass and size distribution. Each native LDL particle contains a single [[apolipoprotein]] B-100 molecule (Apo B-100, a protein with 4536 [[amino acid]] residues) that surrounds the fatty acids keeping them soluble in the aqueous environment.<ref>{{cite journal|journal=Journal of Lipid Research|author=Segrest, J. P. ''et al''|date=September 2001|title=Structure of apolipoprotein B-100 in low density lipoproteins|volume=42|pages=1346-1367}}</ref> The average composition of LDL is approximately 20% [[protein]], 20% [[phospholipids]], 40% cholesteryl esters, 10% unesterified [[cholesterol]], and 5% [[triglycerides]].<ref name="pmid11082530">{{cite journal| author=Hevonoja T, Pentikäinen MO, Hyvönen MT, Kovanen PT, Ala-Korpela M| title=Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL. | journal=Biochim Biophys Acta | year= 2000 | volume= 1488 | issue= 3 | pages= 189-210 | pmid=11082530 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11082530 }} </ref> | |||
==Pathophysiology== | ==Pathophysiology== | ||
Environmental and genetic factors are involved in the pathophysiology of high LDL. Several conditions may contribute to the pathophysiology of high LDL, such as [[Saturated fat|diet high in saturated fat]], [[hypothyroidism]], [[nephrotic syndrome]], [[pregnancy]], [[obesity]], or medications such as [[amiodarone]], [[cyclosporine]], [[diuretics]], and [[glucocorticoids]].<ref name="pmid24239923">{{cite journal| author=Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH et al.| title=2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2014 | volume= 63 | issue= 25 Pt B | pages= 2889-934 | pmid=24239923 | doi=10.1016/j.jacc.2013.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24239923 }} </ref> Abnormally low LDL can occur, and they usually result from rare inherited conditions, such as [[familial hypobetalipoproteinemia]] and [[abetalipoproteinemia]]. | |||
==Causes== | ==Causes== | ||
===Low LDL=== | ===Low LDL=== | ||
Low LDL levels can be caused by unusual inherited disorders of lipoprotein metabolism such as [[abetalipoproteinemia]] and [[hypobetalipoproteinemia]]. | |||
===High LDL=== | ===High LDL=== | ||
High LDL can be primary or secondary to [[Saturated fat|diet high in saturated fat]], [[hypothyroidism]], [[nephrotic syndrome]], [[pregnancy]], [[obesity]], or medications such as [[amiodarone]], [[cyclosporine]], [[diuretics]], and [[glucocorticoids]].<ref name="pmid24239923">{{cite journal| author=Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH et al.| title=2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2014 | volume= 63 | issue= 25 Pt B | pages= 2889-934 | pmid=24239923 | doi=10.1016/j.jacc.2013.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24239923 }} </ref> High LDL can also be caused by [[inherited]] diseases that affect the [[lipid metabolism]]. | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
From 1976–1980 through 2007–2010, for U.S. adults aged 40–74, a decrease was observed in the prevalence of high LDL-cholesterol (LDL–C) from 59% to 28%, as well as an increase in adults using lipid-lowering medications and consuming a diet low in saturated fat. Despite recent advances in medical treatment, high LDL-C remains a significant public health problem in the United States, with more than one-quarter of adults aged 40–74 having high LDL–C.<ref name=Report>Kuklina EV, Carroll MD, Shaw KM, Hirsch R. [http://www.cdc.gov/nchs/data/databriefs/db117.htm Trends in high LDL cholesterol, cholesterol-lowering medication use, and dietary saturated-fat intake: United States, 1976–2010.] NCHS data brief, no 117. Hyattsville, MD: National Center for Health Statistics. 2013.</ref> | |||
==Risk Factors== | ==Risk Factors== | ||
Risk factors for high LDL include [[genetic predisposition]], [[aging]], and unhealthy life style choices. | |||
==Screening== | ==Screening== | ||
According to the [[United states preventive services task force recommendations scheme|United States Preventive Services Task Force (USPSTF)]], screening for high LDL-cholesterol (LDL-c), is indicated among men 35 years and older ([[United states preventive services task force recommendations scheme#USPSTF Grade Definitions|Grade: A Recommendation]]), men age 20 to 35 years in case of an elevated risk for [[coronary heart disease]] ([[United states preventive services task force recommendations scheme#USPSTF Grade Definitions|Grade: B Recommendation]]), women age 45 years and older for in case of an elevated risk for [[coronary heart disease]] ([[United states preventive services task force recommendations scheme#USPSTF Grade Definitions|Grade: A Recommendation]]), and women age 20 to 45 years in case of an elevated risk for [[coronary heart disease]] ([[United states preventive services task force recommendations scheme#USPSTF Grade Definitions|Grade: B Recommendation]]).<ref> Screening for Lipid Disorders in Adults, Topic Page. U.S. Preventive Services Task Force. [http://www.uspreventiveservicestaskforce.org/uspstf/uspschol.htm] </ref> There is insufficient evidence to recommend for or against screening for [[dyslipidemia]] among infants, children, adolescents, or young adults less than 20 years of age ([[United states preventive services task force recommendations scheme#USPSTF Grade Definitions|Grade: I statement]]).<ref> U.S. Preventive Services Task Force. Screening for Lipid Disorders in Children: Recommendation Statement. July 2007.[http://www.uspreventiveservicestaskforce.org/uspstf07/chlipid/chlipidrs.htm]</ref> | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
There is a direct association between cardiovascular death and duration of elevated plasma LDL-cholesterol (LDL-C) levels. In most cases, elevated LDL is a contribution of both polygenic factors and environmental influences.<ref name="pmid12813012">{{cite journal| author=Rader DJ, Cohen J, Hobbs HH| title=Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. | journal=J Clin Invest | year= 2003 | volume= 111 | issue= 12 | pages= 1795-803 | pmid=12813012 | doi=10.1172/JCI18925 | pmc=PMC161432 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12813012 }} </ref> | |||
==Diagnosis== | ==Diagnosis== | ||
Revision as of 01:38, 29 September 2014
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Associate Editor(s)-in-Chief: Rim Halaby, M.D. [4]
Overview
Historical Perspective
From the early 1950s onward, Fredrickson specialized in the study of plasma lipoproteins, compounds of proteins and lipids which transport lipids in the blood. However, the study of lipids in the blood has started early in the 1900's. In 1949, Faraday Society in Birmingham organized the first symposium on lipoproteins and separated for the first time lipoproteins into alpha and beta types. In 1950, LDL was first isolated.[1] In 1973, Myant first hypothesized the role of LDL in the metabolism of cholesterol.[2]
Classification
Prior approaches to the management of LDL aimed towards the classification of LDL concentrations and the treatment of subjects with dyslipidemia to a target LDL concentration. In 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III classified LDL concentrations into optimal, near optimal, borderline high, high, and very high.[3] However, the latest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults no longer takes into consideration LDL cut-off concentration but rather identifies groups of patients among whom the benefit of statin outweighs the risk of adverse events.[4]
Physiology
Low-density lipoprotein (LDL) belongs to the lipoprotein particle family. Its size is approximately 22 nm but since LDL particles contain a changing number of fatty acids they actually have a mass and size distribution. Each native LDL particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein with 4536 amino acid residues) that surrounds the fatty acids keeping them soluble in the aqueous environment.[5] The average composition of LDL is approximately 20% protein, 20% phospholipids, 40% cholesteryl esters, 10% unesterified cholesterol, and 5% triglycerides.[6]
Pathophysiology
Environmental and genetic factors are involved in the pathophysiology of high LDL. Several conditions may contribute to the pathophysiology of high LDL, such as diet high in saturated fat, hypothyroidism, nephrotic syndrome, pregnancy, obesity, or medications such as amiodarone, cyclosporine, diuretics, and glucocorticoids.[4] Abnormally low LDL can occur, and they usually result from rare inherited conditions, such as familial hypobetalipoproteinemia and abetalipoproteinemia.
Causes
Low LDL
Low LDL levels can be caused by unusual inherited disorders of lipoprotein metabolism such as abetalipoproteinemia and hypobetalipoproteinemia.
High LDL
High LDL can be primary or secondary to diet high in saturated fat, hypothyroidism, nephrotic syndrome, pregnancy, obesity, or medications such as amiodarone, cyclosporine, diuretics, and glucocorticoids.[4] High LDL can also be caused by inherited diseases that affect the lipid metabolism.
Epidemiology and Demographics
From 1976–1980 through 2007–2010, for U.S. adults aged 40–74, a decrease was observed in the prevalence of high LDL-cholesterol (LDL–C) from 59% to 28%, as well as an increase in adults using lipid-lowering medications and consuming a diet low in saturated fat. Despite recent advances in medical treatment, high LDL-C remains a significant public health problem in the United States, with more than one-quarter of adults aged 40–74 having high LDL–C.[7]
Risk Factors
Risk factors for high LDL include genetic predisposition, aging, and unhealthy life style choices.
Screening
According to the United States Preventive Services Task Force (USPSTF), screening for high LDL-cholesterol (LDL-c), is indicated among men 35 years and older (Grade: A Recommendation), men age 20 to 35 years in case of an elevated risk for coronary heart disease (Grade: B Recommendation), women age 45 years and older for in case of an elevated risk for coronary heart disease (Grade: A Recommendation), and women age 20 to 45 years in case of an elevated risk for coronary heart disease (Grade: B Recommendation).[8] There is insufficient evidence to recommend for or against screening for dyslipidemia among infants, children, adolescents, or young adults less than 20 years of age (Grade: I statement).[9]
Natural History, Complications and Prognosis
There is a direct association between cardiovascular death and duration of elevated plasma LDL-cholesterol (LDL-C) levels. In most cases, elevated LDL is a contribution of both polygenic factors and environmental influences.[10]
Diagnosis
Laboratory Findings
Treatment
Medical Therapy
Landmark Trials
Future and Investigational Therapies
References
- ↑ "http://dx.doi.org/10.1021/ja01157a121". Retrieved 8 November 2013. External link in
|title=(help) - ↑ Myant NB (1973). "Cholesterol metabolism". J Clin Pathol Suppl (Assoc Clin Pathol). 5: 1–4. PMC 1436101. PMID 4354844.
- ↑ Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). "Executive Summary of The 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)". JAMA. 285 (19): 2486–97. PMID 11368702.
- ↑ 4.0 4.1 4.2 Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH; et al. (2014). "2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 63 (25 Pt B): 2889–934. doi:10.1016/j.jacc.2013.11.002. PMID 24239923.
- ↑ Segrest, J. P.; et al. (September 2001). "Structure of apolipoprotein B-100 in low density lipoproteins". Journal of Lipid Research. 42: 1346–1367.
- ↑ Hevonoja T, Pentikäinen MO, Hyvönen MT, Kovanen PT, Ala-Korpela M (2000). "Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL". Biochim Biophys Acta. 1488 (3): 189–210. PMID 11082530.
- ↑ Kuklina EV, Carroll MD, Shaw KM, Hirsch R. Trends in high LDL cholesterol, cholesterol-lowering medication use, and dietary saturated-fat intake: United States, 1976–2010. NCHS data brief, no 117. Hyattsville, MD: National Center for Health Statistics. 2013.
- ↑ Screening for Lipid Disorders in Adults, Topic Page. U.S. Preventive Services Task Force. [1]
- ↑ U.S. Preventive Services Task Force. Screening for Lipid Disorders in Children: Recommendation Statement. July 2007.[2]
- ↑ Rader DJ, Cohen J, Hobbs HH (2003). "Monogenic hypercholesterolemia: new insights in pathogenesis and treatment". J Clin Invest. 111 (12): 1795–803. doi:10.1172/JCI18925. PMC 161432. PMID 12813012.