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Differentiating hyperlipidaemia associated with antiretroviral therapy
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AIDS 2003; 17(2):189-194. Stefan Mauss a; Juergen Stechel b; Reinhard Willers
c; Guenther Schmutz a; Florian Berger a; Werner O. Richter d
Background: Hyperlipidaemia associated with antiretroviral treatment has led
to concerns for an increased cardiovascular risk in HIV-infected patients.
Objective: To assess this cardiovascular risk by comparing the lipoprotein
pattern of antiretroviral-treated and untreated HIV-positive patients with
patients with familial combined hyperlipidaemia (high cardiovascular risk) or
familial hypertriglyceridaemia (low cardiovascular risk).
Methods: Fasting serum samples were drawn from consecutive patients with HIV
infection or lipoprotein disorders. Total cholesterol, low density
lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol,
triglycerides, apolipoprotein A1 and B were determined in serum. Very low
density lipoprotein (VLDL) was prepared by ultracentrifugation and analysed
for cholesterol, triglycerides and apolipoprotein B.
Results: Lipoprotein disorders were found in 114/187 HIV-positive patients
(61%). Of these, according to the Fredrickson classification, 10% were type
IIa (elevated LDL-cholesterol), 14% type IIb (elevated LDL- and
VLDL-cholesterol) and 76% were type IV (elevated VLDL-cholesterol). VLDL
composition was analysed in 34 HIV-positive patients with type IV
hyperlipidaemia. The ratio of VLDL-triglycerides to VLDL-apolipoprotein B in
these patients was 16.2 ± 6.0. This
ratio was not different from 14 patients with famlial hypertriglyceridaemia
(16.9 ± 6.0; P = 0.61), but differed substantially from 10 patients with
familial combined hyperlipidaemia (6.8 ± 1.0; P < 0.0001).
Conclusions: In HIV-infected patients with high VLDL, large VLDL particles
were found with no increase in number. This pattern resembles familial
hypertriglyceridaemia. It is different from familial combined
hyperlipidaemia, where an increase in number of small-sized VLDL particles
occurs. Further research is needed to assess the contribution of
VLDL-associated
hypercholesterolaemia in those taking antiretroviral drugs to the
cardiovascular risk profile of HIV-positive patients.
Background: Hyperlipidaemia is frequently associated with antiretroviral
treatment and this has led to concerns about an increased cardiovascular risk
in treated HIV-positive patients [1]. The data on cardiovascular events in
HIV-positive patients are anecdotal or retrospective and do not allow firm
conclusions to be drawn regarding the influence of hyperlipidaemia associated
with antiretroviral therapy on cardiovascular risk [2-4]. High-resolution
ultrasound studies assessing intima media thickness and the presence of
atherosclerotic plaques as signs of premature atherosclerosis are conflicting
[5-7]. However, despite the lack of clear evidence, most clinicians assume
that hyperlipidaemia associated with antiretroviral treatment does increase
the cardiovascular risk, and treatment with lipid-lowering agents is common
[8].
It has been shown that hypercholesterolaemia found in HIV-positive patients
is frequently caused by the elevation of very low density lipoprotein (VLDL)
[1, 9-13]. Because of this, the proportion of hyperlipidaemia caused by VLDL
in HIV-positive patients taking antiretroviral therapy is in excess of the
proportion found in the general population. Two well-described genetically
inherited lipid disorders that involve an increase in VLDL may serve as
models to analyse further the lipoprotein pattern in HIV-positive patients
with elevated VLDL and to estimate their cardiovascular risk. Familial
combined hyperlipidaemia is caused by overproduction of small VLDL particles
in the liver, leading to a parallel increase in apolipoprotein B and is
associated with increased cardiovascular risk [14, 15]. Familial
hypertriglyceridaemia is characterized by production of normal numbers of
large VLDL particles containing more triglycerides than normal. This results
in normal apolipoprotein B levels and no or only modestly increased
cardiovascular risk [16, 17].
In the present study, lipoprotein patterns were analysed in HIV-positive
patients with and without antiretroviral treatment, HIV-seronegative patients
with familial combined hyperlipidaemia (high cardiovascular risk) or with
familial hypertriglyceridaemia (low cardiovascular risk). In addition the
size of VLDL particles were measured in a subgroup of
HIV-positive patients who had Fredrickson type IV hyperlipidaemia and this
was compared with that in those with the familial dyslipidaemias.
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