High-density lipoprotein
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2008-07-14T14:55:22Z
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'''High-density lipoproteins''' ('''HDL''') form a class of [[lipoprotein]]s, varying somewhat in their size (8–11 [[nanometer|nm]] in diameter), that carry [[fatty acids]] and [[cholesterol]] from the body's tissues to the [[liver]]. About thirty percent of blood cholesterol is carried by HDL.<ref name="am180">[http://www.americanheart.org/presenter.jhtml?identifier=180 LDL and HDL Cholesterol: What's Bad and What's Good?<!-- Bot generated title -->]</ref>
It is hypothesized that HDL can remove cholesterol from [[atheroma]] within [[artery|arteries]] and transport it back to the liver for excretion or re-utilization—which is the main reason why HDL-bound cholesterol is sometimes called '''"good cholesterol"''', or HDL-C. A high level of HDL-C seems to protect against [[cardiovascular diseases]], and low HDL cholesterol levels (less than 40 mg/dL) increase the risk for heart disease.<ref name="am180" /> When measuring cholesterol, any contained in HDL particles is considered as protection to the body's cardiovascular health, in contrast to "bad" [[Low density lipoprotein|LDL cholesterol]].
== Structure and function ==
HDL are the smallest of the lipoproteins. They are the densest because they contain the highest proportion of [[protein]]. They contain the A class of [[apolipoprotein]]s.<ref>{{cite web|author= Baylor College of Medicine, Lipids Online|url= http://www.lipidsonline.org/slides/slide01.cfm?q=apolipoprotein&dpg=59|year=January 29, 2001 |accessdate=February 20|accessyear=2006|title=Heterogeneity of HDL}}</ref> The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol, carried internally, from cells they interact with. A [[Blood plasma|plasma]] enzyme called [[lecithin-cholesterol acyltransferase]] (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol) which is then sequestered into the core of the lipoprotein particle eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol molecules into their structure. Thus it is the concentration of large HDL particles which more accurately reflects protective action, as opposed to the concentration of total HDL particles.<ref>Kwiterovich PO. The Metabolic Pathways of High-Density Lipoprotein, Low-Density Lipoprotein, and Triglycerides: A Current Review. Am J Cardiol 2000;86(suppl):5L.</ref> This ratio of large HDL to total HDL particles varies widely and is only measured by more sophisticated lipoprotein assays using either [[electrophoresis]] (the original method developed in the 1970s), or newer [[NMR spectroscopy]] methods (See also: [[Nuclear magnetic resonance|NMR]] and [[spectroscopy]]), developed in the 1990s.
In the [[fight-or-flight response|stress response]], [[serum amyloid A]], which is one of the [[acute phase proteins]] and an apolipoprotein, is under the stimulation of [[cytokine]]s ([[Interleukin 1|IL-1]], [[Interleukin 6|IL-6]]) and [[cortisol]] produced in the [[adrenal cortex]] and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as [[amyloidosis]].
Men tend to have noticeably lower HDL levels, with smaller size and lower cholesterol content, than women. Men also have an increased incidence of [[atherosclerosis|atherosclerotic]] heart disease.
Historically, beginning in the late 1970's cholesterol and lipid assays were promoted to estimate total HDL-cholesterol because such tests used to be far less expensive, by about 50 fold, than measured lipoprotein particle concentrations and subclass analysis. Over time, with continued research, decreasing costs, greater availability and wider acceptance of other "lipoprotein subclass analysis" assay methods, including [[NMR spectroscopy]], human studies have continued to show a stronger correlation between human clinically obvious cardiovascular events and quantitatively measured large HDL-particle concentrations.
==Epidemiology==
Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against [[cardiovascular disease]]s such as ischemic [[stroke]] and [[myocardial infarction]]. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) are a positive risk factor for these [[atherosclerotic]] diseases.
Data from the landmark [[Framingham Heart Study]] showed that for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. Conversely, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high. <!--The prior sentences make more sense than this garbled explanation of it...So, for example, for a fixed LDL level of 220 mg/dl, the risk of coronary heart disease is 3-times normal if the HDL is low (25 mg/dl) but just one-third of normal if the HDL is high (85 mg/dl). On the other hand, for a fixed HDL level of 85 mg/dl, the risk of coronary heart disease is one-tenth normal if the LDL is low (100 mg/dl) and still only three-tenths of normal if the LDL is high (220 mg/dl). Phrased differently, this data implies that HDL is a more potent risk factor than LDL. Indeed, for a high HDL level (85 mg/dl), the risk of coronary disease remains lower than average even when the LDL level is high. Lowering LDL levels in such people, while of some benefit, merely converts a low risk situation to a very low risk situation.-->
Even people with very low LDL levels are exposed to some increased risk if their HDL levels are not high enough.<ref>Philip Barter, M.D. [http://content.nejm.org/cgi/content/short/357/13/1301 HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events], September 27, 2007; NEJM</ref>
==Recommended range==
The [[American Heart Association]], [[NIH]] and [[National Cholesterol Education Program|NCEP]] provides a set of guidelines for male fasting HDL levels and risk for [[Coronary heart disease|heart disease]].
{| cellpadding=3 cellspacing=0 border=1 style="border-collapse:collapse"
|bgcolor="#cccccc"| '''Level''' [[gram per litre|mg/dL]]
|bgcolor="#cccccc"| '''Level''' [[Mole (unit)|mmol]]/[[Litre|L]]
|bgcolor="#cccccc"| '''Interpretation'''
|-
| <40
| <1.03
| Low HDL cholesterol, heightened risk for heart disease, <50 is the value for women
|-
| 40–59
| 1.03–1.52
| Medium HDL level
|-
| >60
| >1.55
| High HDL level, optimal condition considered protective against heart disease
|}
More sophisticated laboratory methods measure not just the total HDL but also the range of HDL particles, e.g. "lipoprotein subclass analysis", typically divided into several groups by size, instead of just the total HDL concentration as listed above. The largest groups (most functional) of HDL particles have the most protective effects. The groups of smallest particles reflect HDL particles which are not actively transporting cholesterol, thus not protective.
==Memory==
A link has been shown between level of HDL and onset of dementia. Those with high HDL were less likely to have dementia.<ref>[http://www.nytimes.com/2008/07/01/health/research/01agin.html New York Times July 1st 2008]</ref> Low HDL-C in late-middle age has also been associated with memory loss. <ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18591462&dopt=Abstract]</ref>
==Raising HDL==
===Drugs===
As of 2006, randomized clinical trials have demonstrated significant reduction of atherosclerosis progression and cardiovascular events with treatments that increase HDL-cholesterol (nicotinic acid or a fibrate).<ref name="ehjs">Reducing risk by raising HDL-cholesterol: the evidence. # European Heart Journal Supplements Vol 8 Suppl F p. F23-F29 http://eurheartjsupp.oxfordjournals.org/cgi/content/abstract/8/suppl_F/F23</ref>
Pharmacological therapy to increase the level of HDL cholesterol includes use of [[fibrate]]s and [[niacin]]. Consumption of pharmacologic doses of niacin, an immediate release crystalline form of Vitamin B3, can increase HDL levels by 10–30%<ref>{{cite web|url=http://www.medscape.com/viewarticle/479499_5|accessdate=December 16|accessyear=2007|title=Raising HDL in Clinical Practice}}</ref>
, and is the most powerful agent currently available to increase HDL-cholesterol.<ref name="ehjs" /><ref name="rhcrcr">Raising HDL-Cholesterol and Reducing Cardiovascular Risk. Medscape Cardiology http://www.medscape.com/viewarticle/520393</ref><ref>Chapman M, Assmann G, Fruchart J, Shepherd J, Sirtori C. ''Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid - a position paper developed by the European Consensus Panel on HDL-C''. Cur Med Res Opin. 2004 Aug;20(8):1253-68. {{PMID|15324528}}</ref>
The use of [[statins]] is effective against high levels of LDL cholesterol, but it has little or no effect in raising HDL-cholesterol. <ref name="rhcrcr" /> The use of [[antioxidants]] in combination with statin and niacin therapy reduces the effectiveness of niacin by 33%. (NIH HATS).
[[Torcetrapib]], a promising new drug developed by Pfizer to raise HDL by inhibition of [[cholesterylester transfer protein|cholesteryl ester transfer protein]] (CETP), was terminated after a greater percentage of patients treated with torcetrapib-[[Lipitor]] combination died compared with patients treated with [[Lipitor]] alone. [[Merck & Co.|Merck]] is currently researching a similar molecule called [[anacetrapib]].
===Diet and lifestyle===
Certain changes in lifestyle can have a positive impact on raising HDL levels:<ref>{{cite web|author= Richard N. Fogoros, M.D.|url= http://heartdisease.about.com/cs/cholesterol/a/raiseHDL.htm|accessdate=July 29|accessyear=2006|title=Raising Your HDL Levels}}</ref>
* [[Aerobic exercise]]<ref>Spate-Douglas, T., Keyser, R. E. Exercise intensity: its effect on the high-density lipoprotein profile. ''Arch Phys Med Rehabil 80'', 691-695. {{PMID|10378497}}</ref>
* [[Weight loss]]
* [[Smoking cessation]]
* Removing [[trans fat|trans fatty acids]] from the diet
* One to two drinks of [[alcohol]] a day - HDL transports cholesterol to the liver and cholesterol is known to have a protective effect on the cell membrane. It is likely that this reflects the liver's need for more cholesterol to protect itself from the alcohol:<ref>{{ cite web|author=Gerdi Weidner, PhD; Sonja L. Connor, MS, RD; Margaret A. Chesney, PhD; John W. Burns, MA; William E. Connor, MD; Joseph D. Matarazzo, PhD; and Nancy R. Mendell, PhD|url=http://circ.ahajournals.org/cgi/reprint/83/1/176.pdf|accessyear=2008|accessdate=March 14|title=Sex, alcohol, and HDL - high-density lipoprotein cholesterol; Family Heart Study, Portland, Oregon}}</ref>
* Adding [[monounsaturated fat|monounsaturated]] and [[polyunsaturated fat|polyunsaturated]] fats to the diet, and reducing or eliminating [[saturated fat]]s.
* Adding [[Dietary fiber|soluble fiber]] to diet
Other suggested lifestyle changes include{{Who|date=December 2007}}:
* Using supplements such as [[omega 3]] fish oil
* Limiting intake of dietary fat to 30–35% of total calories
==See also==
* [[Asymmetric dimethylarginine]]
* [[Cardiovascular disease]]
* [[Endothelium]]
* [[Low density lipoprotein]]
==Footnotes==
<references />
==External links==
*[http://www.bajarcolesterol.com/hdl-colesterol/hdl-colesterol.html El hdl]
*[http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm Adult Treatment Panel III Full Report]
*[http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm ATP III Update 2004]
{{Lipoproteins}}
[[Category:Lipid disorders]]
[[Category:Cardiology]]
[[Category:Lipoproteins]]
[[de:High Density Lipoprotein]]
[[es:Lipoproteína de alta densidad]]
[[fr:Lipoprotéine de haute densité]]
[[it:Lipoproteine ad alta densità]]
[[pl:Lipoproteina wysokiej gęstości]]
[[pt:Lipoproteína de alta densidade]]
[[ru:Липопротеины высокой плотности]]
[[sv:Low density lipoprotein]]
[[tr:Yüksek yoğunluklu lipoprotein]]
[[zh:高密度脂蛋白]]