Characterization of functionality of HDL in patients with familial hypercholesterolemia

Heterozygous familial hypercholesterolemia (FH) is characterized by high plasma
concentrations of atherogenic low-density lipoprotein cholesterol (LDL) due to
a mutation in the LDL-receptor gene. Clinically, FH results in tendinous
xanthomas and premature coronary heart disease.
LDL plays a key role in the deposition of cholesterol in the arterial wall,
leading to atherosclerotic plaque formation; this process is intimately
associated with induction of oxidative stress in arterial wall cells. This
oxidative stress leads to formation of oxidized LDL, which has multiple
atherogenic properties.
High-density lipoprotein cholesterol (HDL) has cardioprotective properties such
as: reverse cholesterol transport from the arterial wall and the capacity to
protect LDL against oxidative stress. However, HDL particles are highly
heterogeneous in their anti-oxidative activities. There are suggestions that
the functionality of HDL in FH patients is diminished and that elevated levels
of HDL-associated acute-phase proteins, such as serum amyloid protein A (SAA)
are present. It is believed that these proteins displace apoA-1 from the HDL
particle, which could make HDL small en dense and decrease its anti-oxidant
properties.
However, data on HDL functionality in FH patients are scarce. Because of the
high prevalence of cardiovascular disease in FH patients, it is important to
explore the functionality of HDL in more detail in these patients. Ultimately,
this could lead to better treatment strategies for this population.

1. to investigate whether the known chronic inflammatory and hyperoxidative
state in patients with severely increased LDL is associated with dysfunctional
HDL.
2. to investigate whether CVD in FH is associated with dysfunctional HDL.

Observational, cross-sectional

Not applicable