& Healing Centre
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Cholesterol Balance.
According to the lipid hypothesis, abnormally high cholesterol
levels (hypercholesterolemia), or, more correctly, higher concentrations of LDL
(Low-density lipoprotein) and lower concentrations of functional HDL are
strongly associated with cardiovascular disease because these promote atheroma
development in arteries (atherosclerosis). This disease process leads to
myocardial infarction (heart attack), stroke and peripheral vascular disease.
Since higher blood LDL, especially higher LDL particle concentrations and
smaller LDL particle size, contribute to this process more than the cholesterol
content of the LDL particles, LDL particles are often termed "bad cholesterol"
because they have been linked to atheroma formation. On the other hand, high
concentrations of functional HDL, which can remove cholesterol from cells and
atheroma, offer protection and are sometimes referred to colloquially as "good
cholesterol". These balances are mostly genetically determined but can be
changed by body build, medications, food choices and other factors.
Conditions with elevated concentrations of oxidized LDL particles, especially
"small dense LDL" (sdLDL) particles, are associated with 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 identified
as a mechanism by which cholesterol and inflammatory mediators can be removed
from atheroma. Increased concentrations of HDL correlate with lower rates of
atheroma progressions and even regression. A 2007 study pooling data on almost
900,000 subjects in 61 cohorts demonstrated that blood total cholesterol levels
have an exponential effect on cardiovascular and total mortality, with the
association more pronounced in younger subjects. Still, because cardiovascular
disease is relatively rare in the younger population, the impact of high
cholesterol on health is still larger in older people.
Elevated levels 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. Recently, a post-hoc
analysis of the IDEAL and the EPIC prospective studies found an association
between high levels of HDL cholesterol (adjusted for apolipoprotein A-I and
apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on
the cardioprotective role of "good cholesterol"
Multiple human trials utilizing HMG-CoA reductase inhibitors, known as statins,
have repeatedly confirmed that changing lipoprotein transport patterns from
unhealthy to healthier patterns significantly lowers cardiovascular disease
event rates, even for people with cholesterol values currently considered low
for adults. As a result, people with a history of cardiovascular disease may
derive benefit from statins irrespective of their cholesterol levels, and in men
without cardiovascular disease there is benefit from lowering abnormally high
cholesterol levels ("primary prevention"). Primary prevention in women is
practiced only by extension of the findings in studies on men, since in women,
none of the large statin trials has shown a reduction in overall mortality or in
cardiovascular end points.
The 1987 report of National Cholesterol Education Program, Adult Treatment
Panels suggest the total blood cholesterol level should be: < 200 mg/dL normal
blood cholesterol, 200–239 mg/dL borderline-high, > 240 mg/dL high cholesterol.
The American Heart Association provides a similar set of guidelines for total
(fasting) blood cholesterol levels and risk for heart disease:
Level mg/dL Level mmol/L Interpretation
< 200 < 5.0 Desirable level corresponding to lower risk for heart disease
200–240 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.
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 (or a variant): [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 eight hours
before the blood test because the triglyceride level varies significantly with
food intake.
Given the well-recognized role of cholesterol in cardiovascular disease, it is
surprising that some studies have shown an inverse correlation between
cholesterol levels and mortality in subjects over 50 years of age—an 11%
increase overall and 14% increase in CVD mortality per 1 mg/dL per year drop in
cholesterol levels. In the Framingham Heart Study, the researchers attributed
this phenomenon to the fact that people with severe chronic diseases or cancer
tend to have below-normal cholesterol levels. This explanation is not supported
by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all
ages and women over 50 with very low cholesterol were increasingly likely to die
of cancer, liver diseases, and mental diseases. This result indicates that the
low cholesterol effect occurs even among younger respondents, contradicting the
previous assessment among cohorts of older people that this is a proxy or marker
for frailty occurring with age.
A small group of scientists, united in The International Network of Cholesterol
Skeptics, continues to question the link between cholesterol and
atherosclerosis. However, the vast majority of doctors and medical scientists
accepts the link as fact.
