Distribution of Cholesterol
The greater part of the remaining cholesterol in serum is in HDL, unless
there is hypertriglyceridaemia, and the concentration of this HDL-C
is inversely related to the likelihood of developing CHD.
Normal distribution of cholesterol
In healthy individuals, the remainder of the serum cholesterol is in VLDL,
the level of which is lower than that in HDL when serum triglyceride,
and hence VLDL, are normal. VLDL-cholesterol (VLDL-C), like LDL-C, shows
a positive relationship to CHD risk. Under normal circumstances, chylomicron
cholesterol contributes very little to the total serum cholesterol concentration,
even postprandially.
Abnormal distribution of cholesterol
In type V hyperlipoproteinaemia (see later), in which both VLDL and
chylomicron levels are grossly elevated and there is marked hypertriglyceridaemia,
the greatest part of the serum cholesterol can be in VLDL and chylomicrons
and levels can exceed 20 mmol/L (800 mg/dL; triglycerides are, of course,
higher still).
In the fasting state, serum triglycerides are distributed principally
in VLDL.
What happens to lipoproteins after a meal?
Following a meal, chylomicrons are secreted by the gut and serum triglycerides
usually rise.
Normal response
In healthy individuals consuming a meal that is not especially high
in fat, this rise, may, however, be very small, due to rapid clearance
of chylomicrons, which are hydrolysed by lipoprotein lipase in preference
to the smaller VLDL particles. The proportion of total serum triglyceride
contributed by LDL is much less than VLDL, with HDL containing even
less.
Abnormal response
When hypertriglyceridaemia occurs in association with elevated levels
of LDL-C, it further increases the likelihood of the development of
atheroma and risk of myocardial infarction (see Figure 5). This could
be due to one (or more) of the following:
- the association of this combination with low serum HDL-C;
- an increase in circulating IDL and delayed clearance of chylomicron
remnants;
- an association with smaller LDL particles, which are more readily
oxidised; or
- associated increases in the coagulability of blood caused by increased
plasma fibrinogen levels and factor VII activity.
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| Figure 5. Risk of myocardial infarction
over six years |
Effects on atherosclerosis
When triglyceride-rich lipoproteins are increased without any increase
in LDL, the effect on risk for clinical atherosclerosis can be variable
and cannot always be predicted simply on the basis of the triglyceride
level. Modest elevations of triglycerides can be associated with low
HDL-C and increased small dense LDL (see earlier) and considerably increased
CHD risk; while severe hypertriglyceridaemia in familial lipoprotein
lipase deficiency, type I hyperlipoproteinaemia (see later), does not
generally increase CHD risk. This is perhaps because lipoprotein lipase
activity is necessary for the formation of LDL. On the other hand, in
diabetes, for example, any degree of hypertriglyceridaemia increases
CHD risk, and this risk probably relates more directly to the degree
of hypertriglyceridaemia.
Development of acute pancreatitis
There is also an increased likelihood of acute pancreatitis in all types
of severe hypertriglyceridaemia (both primary and secondary) [Durrington,
1995a], particularly when serum triglyceride levels exceed 20-30 mmol/L
(2000-3000 mg/dL). The cause of this is not known for certain, but it
may be because of direct damage to the pancreas by free fatty acids (released
as a result of lipolysis owing to pancreatic lipase leaking into pancreatic
capillaries), or because of pancreatic damage caused by the products of
lipid peroxidation. Both of these would be enhanced when increased concentrations
of large triglyceride-rich lipoproteins move sluggishly through the pancreatic
microcirculation.
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