The SA Journal Diabetes & Vascular Disease Vol 15 No 2 (November 2018)

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SA JOURNAL OF DIABETES & VASCULAR DISEASE RESEARCH ARTICLE
VOLUME 15 NUMBER 2 • NOVEMBER 2018 55
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 increased NO levels due to statin therapy
was observed at the end of a six-month treatment period.24,25 On
the other hand, Marchesi et 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 ΔLDL 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.
References
1. Forte L, Cimmino G, Loffredo F, De Palma R, Abbate G, Calabrò P, et al. C-reactive
protein is released in the coronary circulation and causes endothelial dysfunction
in patients with acute coronary syndromes. Int J Cardiol 2011; 152(1): 7–12.
2. Marzilli M. Pleiotropic effects of statins: evidence for benefits beyond LDL-
cholesterol lowering. Am J Cardiovasc Drugs 2010; 10(Suppl 1): 3–9.
3. Hermida N, Balligand JL. Low-density lipoprotein-cholesterol-induced endothelial
dysfunction and oxidative stress: the role of statins. Antioxid Redox Signal 2014;
20(8): 1216–1237.
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1) Crepaldi G and Fioretto P. Gliclazide modified release: Its place in the therapeutic armamentarium. Metabolism
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