Cardiovascular Journal of Africa: Vol 29 No 3 (May/Junel 2018)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018 AFRICA 165
non-invasive, easily applicable and repeatable method. Studies
have demonstrated that FMD was correlated with endothelial
function, making it a good marker of endothelial function.13,14
In the MERCURY I trial, eight-week atorvastatin 20 mg/
day and rosuvastinin 10 mg/day therapies were compared in
terms of achieving target LDL-C values of NCEP ATPIII; 80%
of the patients in the rosuvastatin group and 74% of those in
the atorvastatin group achieved target LDL-C values.15 In the
SOLAR trial, either atorvastatin 10 mg/day, rosuvastatin 10 mg/
day or simvastatin 20 mg/day was administered as the initial dose
for six weeks in 1 634 high-risk patients. The dose was doubled
in patients who failed to achieve target value at the end of six
weeks. At the end of 12 weeks, target values were achieved with
rosuvastatin in 76% of patients, with atorvastatin in 58%, and
with simvastatin in 53%.16 It is known that atorvastatin 20 mg
is pharmacokinetically the same as rosuvastatin 10 mg.17 In the
present study, LDL cholesterol level decreased with both statins
at the end of the 12th month versus baseline, but no statistically
significant difference was found between the groups.
The effect of different doses of atorvastatin and rosuvastatin
on HDL levels varies according to clinical setting and patient
characteristics. The size of the increase is generally more
signifcant with lower baseline values. Additionally, the effect
is moderate compared to niacin or fibrates. The elevation of
HDL level ranges from five to 13%.18 In our study, the amount
of elevation was not significant, which could have been due to
low-dose statin usage or the relatively higher baseline HDL levels
of the subjects.
Cardiovascular risk factors such as hyperlipidaemia
contribute to endothelial dysfunction, which is the first
step in atherogenesis. Although the concurrent presence of
hyperlipidaemia and endothelial dysfunction is frequently
encountered, the mechanism is unclear. However, oxidised
LDL cholesterol is thought to cause endothelial injury. Many
studies have demonstrated that endothelium-dependent (flow-
mediated) dilation is enhanced with increased duration of the
endothelium’s exposure to oxidised LDL.19-21
Kawano et al. demonstrated impaired flow-mediated dilation
in an experimental model of acute hyperglycaemia in healthy
adults on a fatty diet.22 Harrison et al. reported improvement in
endothelial function due to decreased cholesterol in the diet.23 In
studies on statins, the time for endothelial function to improve
ranged from hours to months. In earlier studies, improvement in
endothelial function with increasedNO levels due to statin therapy
was observed at the end of a six-month treatment period.24,25 On
the other hand, Marchesiet al. observed remarkable improvement
in endothelial function after a two-week atorvastatin therapy in
postmenopausal women with hyperlipidaemia.26
In the present study, a 22.3 and 30.9% ( p = 0.122) increase in
FMD was observed in both atorvastatin and rosuvastatin groups,
respectively, after 12 months of statin therapy. Improvement in
FMD showed no correlation with post-treatment LDL levels.
We found however that percentage Δ LDL was well correlated
with ΔFMD and ΔEID, which may suggest that statins have
a pleiotropic effect independent of their cholesterol-lowering
effects. Similarly, ΔLDL was also found to be well correlated
with ΔFMD and ΔEID values. In other words, endothelial
function was statistically significantly improved at the end of
12-month statin therapy, in parallel with ΔLDL, among patients
with hyperlipidaemia.
Although endothelium-independent dilation increased in both
groups, the increase was not statistically significantly different.
Increased brachial artery basal diameter after 12 months of
treatment, which was more pronounced in the rosuvastatin group,
reached a value close to the diameter obtained for baseline FMD,
due probably to increased NO levels. More prominent increases
in FMD and basal diameter in the rosuvastatin group suggest
that the NO-secreting effect from the endothelium induced by
rosuvastatin was more significant than that by atorvastatin.
There are some limitations of the present study, such as
limited patient numbers, as well as not measuring blood NO
and asymmetric di-methyl arginine levels due to technical issues.
In addition, the technique for measuring FMD depends on the
experience of the person carrying it out.
Conclusion
In this study, both atorvastatin 20 mg/day and rosuvastatin
10 mg/day therapies given to hyperlipidaemic patients for one
year provided significant benefits on endothelial function.
The data from non-invasive evaluations found that although
the favourable effects of rosuvastatin on the endothelium may
have been relatively more prominent compared to those of
atorvastatin, there was no statistically significant difference.
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