Hyper-Cholesterolemia
Main articles: hyper-cholesterolemia and lipid hypothesis
According to the lipid hypothesis,
abnormal cholesterol levels (hyper-cholesterolemia) —
actually higher concentrations of LDL particles
and lower concentrations of functional HDL particles
— 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 HDL
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 as "good
cholesterol". These balances are mostly genetically determined, but can be
changed by body build, medications, food
choices, and other factors. Resistin, a protein
secreted by fat tissue, has been shown to increase the production of LDL in
human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to
clear cholesterol from the bloodstream. Resistin accelerates
the accumulation of LDL in arteries, increasing the risk of heart disease.
Resistin also adversely impacts the effects of statins, the main
cholesterol-reducing drug used in the treatment and prevention of
cardiovascular disease.
Conditions with
elevated concentrations of oxidized LDL particles, especially "small dense
LDL" (sdLDL) particles, are associated with atheromaformation 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. 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".
Elevated cholesterol
levels are treated with a strict diet consisting of low saturated fat, trans
fat-free, low cholesterol foods, often followed by one of various hypolipidemic agents,
such as statins, fibrates, cholesterol absorption inhibitors,
nicotinic acid derivatives or bile acid sequestrants. Extreme cases have
previously been treated with partial ileal
bypass surgery, which has now been superseded by medication.Apheresis-based treatments are still used for
very severe hyperlipidemias that are either unresponsive to treatment or
require rapid lowering of blood lipids.[citation
needed]
Multiple human trials
using 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.[citation
needed] Studies
have also found that statins reduce atheroma progression. As a result, people
with a history of cardiovascular disease may derive benefit from statins
irrespective of their cholesterol levels (total
cholesterol below 5.0 mmol/L [193 mg/dL]), 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 endpoints.
The
1987 report of National
Cholesterol Education Program, Adult Treatment Panels suggests 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:
|
Interpretation
|
||
|
< 200
|
< 5.2
|
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 upper limit of 70 mg/dL (1.8 mmol/L) 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.
Total cholesterol is defined as
the sum of HDL, LDL, and VLDL. Usually, only the total, HDL, and triglycerides
are measured. For cost reasons, the VLDL is usually estimated as one-fifth of
the triglycerides and the LDL is estimated using the Friedewald formula (or a variant): estimated
LDL = [total cholesterol] − [total HDL] − [estimated VLDL]. VLDL can be
calculated by dividing total triglycerides by five. Direct LDL measures are
used when triglycerides exceed 400 mg/dL. The estimated VLDL and LDL have
more error when triglycerides are above 400 mg/dL.
Given the well-recognized role of
cholesterol in cardiovascular disease, some studies have shown an inverse
correlation between cholesterol levels and mortality. A 2009 study of patients
with acute coronary syndromes found an association of hypercholesterolemia with
better mortality outcomes. In the Framingham Heart Study, in subjects over 50 years of
age, they found an 11% increase overall and 14% increase in cardiovascular
disease mortality per 1 mg/dL per year drop in total cholesterol levels.
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 likely to die of cancer, liver diseases, and mental diseases. This result
indicates 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.
The vast majority of doctors and
medical scientists consider that there is a link between cholesterol and
atherosclerosis as discussed above; a small group of scientists, united in The International Network of
Cholesterol Skeptics, questions the link.
Hypo-cholesterolemia
Abnormally low levels of
cholesterol are termed hypo-cholesterolemia. Research
into the causes of this state is relatively limited, but some studies suggest a
link with depression, cancer, and cerebral
hemorrhage. In general, the low cholesterol levels seem to be a
consequence, rather than a cause, of an underlying illness.
Cholesterol
testing
The American Heart Association recommends
testing cholesterol every five years for people aged 20 years or older.
A blood sample after 12-hour fasting is taken by
a doctor, or a home cholesterol-monitoring device is used to determine a lipoprotein
profile. This measures total cholesterol, LDL (bad) cholesterol, HDL
(good) cholesterol, and triglycerides. It is recommended to test cholesterol at
least every five years if a person has total cholesterol of 5.2 mmol/L or
more (200+ mg/dL), or if a man over age 45 or a woman over age 50 has HDL
(good) cholesterol less than 1 mmol/L (40 mg/dL), or there are other
risk factors for heart disease and stroke.
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