Low density lipoprotein: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 7: Line 7:
==Overview==
==Overview==
'''Low-density lipoprotein''' ('''LDL''') belongs to the [[lipoprotein]] particle family. Its size is approx. 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 circles 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>  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>  Not only does LDL transport cholesterol, but also this activity is key to control cholesterol homeostasis.<ref>Murtola T, Vuorela TA, Hyvonen MT et al. Low density lipoprotein: Structure, dynamics, and interactions of apoB-100 with lipids. Soft Matter. 2011;7:8136-8141</ref> Several factors contribute to the elevation of the LDL levels, such as primary hyperlipoproteinemia, [[diabetes mellitus]], [[hypothyroidism]], high fat diet and [[drugs]].
'''Low-density lipoprotein''' ('''LDL''') belongs to the [[lipoprotein]] particle family. Its size is approx. 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 circles 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>  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>  Not only does LDL transport cholesterol, but also this activity is key to control cholesterol homeostasis.<ref>Murtola T, Vuorela TA, Hyvonen MT et al. Low density lipoprotein: Structure, dynamics, and interactions of apoB-100 with lipids. Soft Matter. 2011;7:8136-8141</ref> Several factors contribute to the elevation of the LDL levels, such as primary hyperlipoproteinemia, [[diabetes mellitus]], [[hypothyroidism]], high fat diet and [[drugs]].
==Measurement Methods==
Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available. However, there is increasing evidence and recognition of the value of more sophisticated measurements. Specifically, LDL particle number (concentration), and to a lesser extent size, have shown much tighter correlation with atherosclerotic progression and cardiovascular events than is obtained using chemical measures of total LDL concentration contained within the particles. LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Alternatively, LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. If LDL particle concentration is tracked against event rates, many other statistical correlates of cardiovascular events, such as [[diabetes mellitus]], obesity and smoking, lose much of their additive predictive power.
===LDL Subtype Patterns===
LDL particles actually vary in size and density, and studies have shown that a pattern that has more small dense LDL particles ("Pattern B") equates to a higher risk factor for [[coronary heart disease]] (CHD) than does a pattern with more of the larger and less dense LDL particles ("Pattern A").  This is because the smaller particles are more easily able to penetrate the [[endothelium]]. "Pattern I", meaning "intermediate", indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm).
The correspondence between Pattern B and CHD has been suggested by some in the medical community to be stronger than the correspondence between the LDL number measured in the standard lipid profile test.  Tests to measure these LDL subtype patterns have been more expensive and not widely available, so the common lipid profile test has been used more commonly.
The lipid profile does not measure LDL level directly but instead estimates it via the Friedewald equation  using levels of other cholesterol such as [[High density lipoprotein|HDL]]:
In mg/dl: LDL cholesterol = total cholesterol – HDL cholesterol – (0.2 × triglycerides)<br />
In mmol/l: LDL cholesterol = total cholesterol – HDL cholesterol – (0.45 × triglycerides)
There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52 mmol/L (400 mg/dL). Even at LDC-L levels 2.5 to 4.5 mmol/L, this formula is considered to be inaccurate.  If both total cholesterol and triglyceride levels are elevated then a modified formulat may be used
LDL-C = Total-C HDL-C (0.16 x TAG)
This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer. (However, the concentration of LDL particles, and to a lesser extent their size, has far tighter correlation with clinical outcome than the content of cholesterol with the LDL particles, even if the LDL-C estimation is about correct.)
There has also been noted a correspondence between higher triglyceride levels and higher levels of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the larger, less dense LDL.
However, cholesterol and lipid assays, as outlined above were never promoted because they worked the best to identify those more likely to have problems, but simply because they used to be far less expensive, by about 50 fold, than measured lipoprotein particle concentrations and subclass analysis. With continued research, decreasing cost, greater availability and wider acceptance of other "lipoprotein subclass analysis" assay methods, including [[NMR spectroscopy]], research studies have continued to show a stronger correlation between human clinically obvious cardiovascular event and quantitatively measured particle concentrations.


==References==
==References==

Revision as of 17:42, 12 September 2013

Low Density Lipoprotein Microchapters

Home

Patient information

Overview

Historical Perspective

Classification

Physiology

Pathophysiology

Causes

Low LDL
High LDL

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Prognosis and Complications

Diagnosis

Laboratory Findings

Treatment

Medical Therapy

Landmark Trials

Future or Investigational Therapies

Case Studies

Case #1

Low density lipoprotein On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Low density lipoprotein

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Low density lipoprotein

CDC on Low density lipoprotein

Low density lipoprotein in the news

Blogs on Low density lipoprotein

Directions to Hospitals Treating Low density lipoprotein

Risk calculators and risk factors for Low density lipoprotein

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]

Synonyms and keywords: LDL-cholesterol, LDL-C

Overview

Low-density lipoprotein (LDL) belongs to the lipoprotein particle family. Its size is approx. 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 circles the fatty acids keeping them soluble in the aqueous environment.[1] 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.[2] Not only does LDL transport cholesterol, but also this activity is key to control cholesterol homeostasis.[3] Several factors contribute to the elevation of the LDL levels, such as primary hyperlipoproteinemia, diabetes mellitus, hypothyroidism, high fat diet and drugs.

References

  1. ↑ Segrest, J. P.; et al. (September 2001). "Structure of apolipoprotein B-100 in low density lipoproteins". Journal of Lipid Research. 42: 1346–1367.
  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.
  3. ↑ Murtola T, Vuorela TA, Hyvonen MT et al. Low density lipoprotein: Structure, dynamics, and interactions of apoB-100 with lipids. Soft Matter. 2011;7:8136-8141



Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Low_density_lipoprotein&oldid=904668"