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Low density lipoprotein

From Wikipedia, the free encyclopedia.

Low-density lipoprotein (LDL) refers to a class and range of

lipoprotein particles, varying somewhat in their size and contents,

which carry cholesterol in the blood and around the body, for use by

various cells.It is the final stage of VLDL (very low-density

lipoprotein) which is produced by the liver. The LDL contains the

apoprotein B-100 (Apo B-100) among is plasma lipids. It is commonly

referred to as " bad cholesterol " due to the link between high LDL

levels and cardiovascular disease.

Contents [hide]

1 Function

2 Role in disease

3 Recommended range

4 LDL Subtype Patterns

5 References

6 See also

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Function

Generally, LDL transports cholesterol and triglycerides away from

cells and tissues that produce more than they use, towards cells and

tissues which are taking up cholesterol and triglycerides.

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Role in disease

Because LDL transports cholesterol to the arteries, increased levels

are associated with atherosclerosis, and thus myocardial infarctions,

strokes and peripheral vascular disease. This is why cholesterol

inside LDL lipoproteins is called bad cholesterol. Still, it is not

the cholesterol that is bad; it is instead how and where it is being

transported, and in what amounts over time.

Increasing evidence has revealed that the concentration and size of

the LDL particles more powerfully relates to the degree of

atherosclerosis progression than the concentration of cholesterol

contained within all the LDL particles. Having low concentrations of

large LDL particles is the healthy pattern. Conversely, high

concentrations of small LDL particles, despite the same total

cholesterol content correlates with much faster growth of atheroma

and progression of atherosclerosis.

LDL is formed as VLDL lipoproteins lose triglyceride through the

action of lipoprotein lipase (LPL), and become smaller and denser

containing a higher proportion of cholesterol.

A hereditary form of high LDL is familial hypercholesterolemia (FH).

Increased LDL is termed hyperlipoproteinemia type II (after the dated

Fredrickson classification).

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Recommended range

The American Heart Association, NIH and NCEP provide a set of

guidelines for fasting LDL levels and risk for heart disease.

Level mg/dl Level mmol/L Interpretation

<100 <2.6 Optimal LDL cholesterol, corresponding to reduced risk for

heart disease

100-129 2.6-3.3 Near optimal LDL level

130-159 3.3-4.1 Borderline high LDL level

160-189 4.1-4.9 High LDL level

>190 >4.9 Very high LDL level, increased risk of heart disease

Over time, with more clinical research, these recommended levels keep

being reduced. For instance, for people with known atherosclerosis

diseases, the 2004 updated American Heart Association, NIH and NCEP

recommendations are for LDL levels to be lowered to less than 70

mg/dL, unspecified how much lower. It has been estimated from the

results of muptiple human pharmacologic LDL lowering trials that LDL

should be lowered to about 50 to reduce cardiovascular event rates to

near zero. For reference, from longitudinal population studies

following progression of atherosclerosis related behaviors from early

childhood into adulthood, it has been discovered that the usual LDL

in childhood, before the development of fatty streaks is about 35

mg/dL. However, all the above values refer to chemical measures of

lipid concentration, probably not the better approach.

Chemical measures of lipid concentration have long been the clinical

measurement of choice 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 much

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 concentration can be low, yet LDL particle

number high and cardiovascular events rates are high. Alternatively,

LDL 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, loose much their additive predictive power.

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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 --

called " Pattern B " -- equates to a higher risk factor for Coronary

Heart Disease (CHD) than does a pattern with more of the

larger " fluffy " 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 (approx 260 Angstroms).

The correspondence between Pattern B and CHD has been suggested by

some in the medical community to be much stronger than the

correspondence between the LDL number measured in the standard lipid

profile test. Tests to measure these LDL subtype patterns are not

widely available, so the common lipid profile test is used more

commonly. The lipid profile does not directly measure LDL particles

but instead calculates their value based on other particle lipids via

the Freidwald equation. 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 fluffier LDL. [1] [2]. However, with

ongoing studies, the stronger correlation has been with

quantitatively measured particle concentrations, more so than

particle size and particle lipid content.

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References

Adult Treatment Panel III Full Report

ATP III Update 2004

HeartPoint: Cholesterol, Advanced Discussion

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See also