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 cholesterol
Cholesterol is a sterol (a combination steroid and alcohol) and a
lipid found in the cell membranes of all body tissues, and transported in the
blood plasma of all animals. Lesser amounts of cholesterol are also found in
plant membranes. The name originates from the Greek chole- (bile) and stereos
(solid), and the chemical suffix -ol for an alcohol, as researchers first
identified cholesterol (C27H45OH) in solid form in gallstones in 1784.
Most cholesterol is not dietary in origin; it is synthesized internally.
Cholesterol is present in higher concentrations in tissues which either produce
more or have more densely-packed membranes, for example, the liver, spinal cord
and brain, and also in atheroma. Cholesterol plays a central role in many
biochemical processes, but is best known for the association of cardiovascular
disease with various lipoprotein cholesterol transport patterns and high levels
of cholesterol in the blood.
Often, when most doctors talk to their patients about the health concerns of
cholesterol, they are referring to "bad cholesterol", or low-density lipoprotein
(LDL). "Good cholesterol" is high-density lipoprotein (HDL).
cholesterol
Hypercholesterolemia
In conditions with elevated concentrations of oxidized LDL particles,
especially small LDL particles, cholesterol promotes atheroma formation in the
walls of arteries,
a condition known as atherosclerosis, which is the principal cause of
coronary heart disease and other forms of cardiovascular disease. In contrast,
HDL particles (especially large HDL) have been the only identified mechanism by
which cholesterol can be removed from atheroma. Increased concentrations of HDL
correlate with lower rates of atheroma progressions and even regression.
Of the lipoprotein fractions, LDL, IDL and VLDL are regarded as
atherogenic (prone to cause atherosclerosis). Levels of these fractions,
rather than the total cholesterol level, correlate with the extent and progress
of atherosclerosis. Conversely, the total cholesterol can be within normal
limits, yet be made up primarily of small LDL and small HDL particles, under
which conditions atheroma growth rates would still be high. In contrast,
however, if LDL particle number is low (mostly large particles) and a large
percentage of the HDL particles are large, then atheroma growth rates are
usually low, even negative, for any given total cholesterol concentration.
These effects are further complicated by the relative concentration of
asymmetric dimethylarginine (ADMA) in the endothelium, since ADMA down-regulates
production of nitric oxide, a relaxant of the endothelium. Thus, high levels of
ADMA, associated with high oxidized levels of LDL pose a heightened risk factor
for cardiovascular disease.
Multiple human trials utilizing HMG-CoA reductase inhibitors or statins,
have repeatedly confirmed that changing lipoprotein transport patterns from
unhealthy to healthier patterns significantly lower cardiovascular disease event
rates, even for people with cholesterol values currently considered low for
adults; however, no statistically significant mortality benefit has been
derived to date by lowering cholesterol using medications in asymptomatic
people, i.e., no heart disease, no history of heart attack, etc.
Some of the better-designed recent randomized human outcome trials studying
patients with coronary artery disease or its risk equivalents include the Heart
Protection Study (HPS), the PROVE-IT trial, and the TNT trial. In addition,
there are trials that have looked at the effect of lowering LDL as well as
raising HDL and atheroma burden using intravascular ultrasound. Small trials
have shown prevention of progression of coronary artery disease and possibly a
slight reduction in atheroma burden with successful treatment of an abnormal
lipid profile.
The
American Heart Association provides a set of guidelines for total (fasting)
blood cholesterol levels and risk for heart disease:
| Level
mg/dL |
Level
mmol/L |
Interpretation |
| <200 |
<5.2 |
Desirable level corresponding to lower risk for heart disease |
| 200-239 |
5.2-6.2 |
Borderline high risk |
| >240 |
>6.2 |
High risk |
However, as today's testing methods determine LDL ("bad") and HDL ("good")
cholesterol separately, this simplistic view has become somewhat outdated. The
desirable LDL level is considered to be less than 100 mg/dL (2.6 mmol/L),
although a newer target of <70 mg/dL can be considered in higher risk
individuals based on some of the above-mentioned trials. A ratio of total
cholesterol to HDL —another useful measure— of far less than 5:1 is thought to
be healthier. Of note, typical LDL values for children before
fatty streaks begin to develop is 35 mg/dL.
Patients should be aware that most testing methods for LDL do not actually
measure LDL in their blood, much less particle size. For cost reasons, LDL
values have long been estimated using the Friedewald formula: [total
cholesterol] − [total HDL] − 20% of the
triglyceride value = estimated LDL. The basis of this is that Total
cholesterol is defined as the sum of HDL, LDL, and VLDL. Ordinarily just the
Total, HDL, and Triglycerides are actually measured. The VLDL is estimated as
one-fifth of the Triglycerides. It is important to fast for at least 8-12 hours
before the blood test because the triglyceride level varies significantly with
food intake.
Increasing clinical evidence has strongly supported the greater predictive
value of more-sophisticated testing that directly measures both LDL and HDL
particle concentrations and size, as opposed to the more usual
estimates/measures of the total cholesterol carried within LDL particles or the
total HDL concentration.
Hypocholesterolemia
Abnormally low levels of cholesterol are termed hypocholesterolemia.
Research into the causes of this state is relatively limited, and while some
studies suggest a link with depression, cancer and
cerebral hemorrhage it is unclear whether the low cholesterol levels are a cause
for these conditions or an epiphenomenon. |
