Variation of non-cholesterol sterol levels in a population of mildly hypercholesterolaemic subjects

Intestinal cholesterol absorption varies considerably in the general
population, ranging between 20-70%. Previous studies have suggested a
classification of subjects with high or low cholesterol absorption. In most
studies, levels of non-cholesterol sterols have been used as markers for
cholesterol absorption and synthesis respectively. Based on these markers, a
classification of subjects with high or low absorption, the so called high and
low absorbers, has been suggested. The high absorbers are thought to have
elevated cholesterol levels due to high absorption, whereas the low absorbers
have elevated levels based on high synthesis. Subsequently, it has been
suggested that high absorbers do not or hardly benefit from statin treatment
alone, either with respect to cholesterol reduction and the recurrence of CHD.
Therefore, the high absorbers may benefit from the addition of cholesterol
absorption inhibitors.

This underscores the need to identify high absorbers in order to treat them
accurately.
Therefore, easy accessible markers are essential in clinical practice. However,
whether high and low absorbers indeed can be identified based on plasma levels
of non-cholesterol sterols has never been verified by means of actual
cholesterol absorption measurement. Besides the fact that the validity of these
markers may be questionable, they also do not provide any indication regarding
the quantity of cholesterol that is absorbed.

In a future study, we will investigate the actual cholesterol absorption rates
in mildly hypercholesterolaemic subjects, who are predefined as high and low
absorbers based on their plasma levels of non-cholesterol sterols. In order to
do so, we will first measure non-cholesterol sterol levels in a relatively
large population of mildly hypercholesterolaemic, but otherwise healthy,
subjects. This will be done in the current study.
Hereby we can determine the variation of non-cholesterol sterol levels in this
population in order to evaluate whether this corresponds to the variation in
cholesterol absorption markers previously found in literature. In addition, we
will investigate whether genetic variation in genes coding for proteins
involved in cholesterol homeostasis, such as NPC1L1 and ABCG5 and G8, can
explain the variability in non-cholesterol sterol data. Combined with the data
of the future cholesterol absorption studies, this genetic variation might
explain variation in cholesterol homeostasis between high and low cholesterol
absorbers.

Primary Objective: What is the variation in non-cholesterol sterol levels in a
large population of mildly hypercholesterolaemic, but otherwise healthy
subjects?
Secondary Objective: Can genetic variation in proteins involved in cholesterol
homeostasis, such as Niemann-Pick C1-like 1 (NPC1L1) and the ATP binding
cassette (ABC) G5 and G8 halftransporters, explain the variation in
non-cholesterol sterols?
In addition, this study will be used for selection of participants for our
future studies.

A cross-sectional cohort study. The study comprises a single measurement of
non-cholesterol sterol and lipoprotein levels in 160 mildy
hypercholesterolemic, but otherwise healthy volunteers.

Hardly any risks are involved in this study. A single venepuncture, during
which a maximum of 50ml blood will be collected, will be done. In case
participants are already treated with cholesterol lowering medication, they
will be asked to discontinue this medication during a 6-week period. These
volunteers will undergo a second venepuncture. We do not expect any unfavorable
effects of discontinuation of this medication during 6 weeks.