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SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
VOLUME 15 NUMBER 2 • NOVEMBER 2018
53
A subject was considered treatment adherent when he/she
took her/his prescribed statin regularly on a daily basis. A subject
was considered complient if his/her baseline and post-treatment
measurements were obtained as per the study protocol. Eight
cases (four with compliance problems with follow up, one with
lung cancer and three with non-adherence to medication) were
excluded from the study.
The study was completed with 104 hyperlipidaemic patients, of
whom 50 were assigned to atorvastatin 20 mg per day and 54
to rosuvastatin 10 mg per day. Patients under the age of 18 and
over the age of 80 years, those with heart failure, uncontrolled
hypertension, endocrine diseases, previous coronary artery disease,
frequent and permanent cardiac dysrhythmia, malignancy, chronic
obstructive pulmonary disease, and chronic liver, kidney, neurological
or psychiatric diseases, which were likely to produce a compliance
problem, were not included in the study.
Baseline demographic characteristics of the patients were
recorded. Body mass index (BMI) was calculated as body weight
(kg)/height
2
(m). Levels of fasting blood glucose, serum total
cholesterol, high-density lipoprotein (HDL) cholesterol, low-density
lipoprotein (LDL) cholesterol, triglycerides (TG), urea, creatinine,
aspartate transaminase (AST), alanine transaminase (ALT), creatinine
phosphokinase (CPK) and complete blood counts were measured in
all patients after a 12-hour fasting period. In addition, the patients
underwent transthoracic echocardiography.
Lipid levels indicated eligible patients, who were randomly
assigned to receive either rosuvastatin 10 mg/day or atorvastatin
20 mg/day. The patients were followed for one year. Baseline
measurements were repeated at the end of the 12-month treatment
period. Change in LDL level (ΔLDL) was defined as the difference
between baseline and post-treatment LDL values.
Endothelial function was measured ultrasonographically over
the brachial artery using echocardiography (Ge-Vivid 7 Pro, General
Electric, Florida, USA) with a 12-L probe.
All measurements were performed according to the method
described elsewhere in the literature.
11
Brachial artery basal Doppler
velocity (DV), basal diameter (BD), brachial artery hyperaemia velocity
(HV), and post-flow brachial artery lumen diameter (hyperaemia
diameter = HD flow-mediated dilation response = FMDR) were
recorded. FMD was calculated from the following equation:
% FMD = FMDR – BD
BD
× 100
Baseline endothelium-independent dilation (EID) was measured
10 minutes after deflation of the cuff to obtain baseline conditions
and was labelled as pre-nitrate BD. Thereafter, the patients received
400 μg of nitroglycerin sublingually; three to five minutes later,
post-nitrate Doppler, post-nitrate velocity (NTGV) and post-nitrate
arterial diameter (NTGD) were measured. Lumen diameter was
measured three times and the arithmetic mean was calculated.
Post-nitrate arterial diameter was named nitrate-mediated dilation
response (NMDR). EID was calculated using the following equation:
% EBG = NMDR – pre-nitrate BD
Pre-nitrate BD
× 100
ΔFMD and ΔEID were defined as the difference between baseline
and post-treatment FMD and EID values, respectively.
Statistical analyses
The SPSS (SPSS, Inc, Chicago, IL, USA) program was used to
analyse the data. Mean and standard deviations (SD) were used
for descriptive data. Student’s
t
-test was used to compare normally
distributed quantitative variables, whereas the Mann–Whitney
U
-test was used to compare independent non-normally distributed
quantitative variables. Moreover, statistical comparison between
continuous dependent variables was done by paired-samples
t
-test
for normally distributed variables, whereas the Wilcoxon test was
used for non-normally distributed variables. Relationships between
the parameters were assessed with Pearson’s correlation analysis
for parametric variables and by Spearman’s correlation analysis for
non-parametric variables. The results were evaluated with a 95%
confidence interval and at the significance level of
p
< 0.05.
Results
A total of 104 hyperlipidaemic cases were included in the study. The
patients were randomly assigned to either atorvastatin (group 1,
n
=
50, 48.1%) or rosuvastatin (group 2,
n
= 54, 51.9%) therapy. Of the
overall patients, 46 were male (53.7 ± 9.7 years) and 58 were female
(54.3 ± 10.1 years). There was no statistically significant difference
between the two groups in terms of baseline anthropometric
characteristics of the subjects, haemoglobin, haematocrit, white
blood cell count, thrombocyte count, and urea, creatinine, AST, ALT,
CPK, total cholesterol, TG, HDL and LDL levels.
Mean ΔLDL at the end of 12 months was 71.0 ± 29.7 mg/dl
(1.84 ± 0.77 mmol/l) and percentage ΔLDL was 42.2 ± 17.6% (
n
= 104) in the study population. ΔLDL was significantly correlated
with ΔFMD (
r
= 0.367,
p
< 0.005) and ΔEID (
r
= 0.523,
p
< 0.001).
Percentage ΔLDL was statistically correlated with ΔFMD (
r
= 0.412,
p
< 0.005) and ΔEID (
r
= 523,
p
< 0.001). In the atorvastatin group,
a statistically significant reduction was shown in total cholesterol,
LDL and TG levels compared to baseline values. LDL level showed
a 52.5% decrease after 12 months compared to baseline value,
whereas no decrease was observed in HDL level. FMD showed a
statistically significant increase (Table 1).
In the rosuvastatin group, a statistically significant decrease
was found in total cholesterol, LDL and TG levels compared to
Table 1.
Post-treatment versus baseline values in the atorvastatin group
Baseline
12-month
Atorvastatin
mean ± (SD)
mean ± (SD)
p
-value*
Basal diameter (mm)
4.0 ± 0.6
4.1 ± 0.6
0.045
Hyperaemia diameter (mm)
4.2 ± 0.6
4.3 ± 0.6
0.436
NTG diameter (mm)
4.5 ± 0.6
4.7 ± 0.6
0.002
FMD (%)
8.5 ± 3.3
10.4 ± 4.1
< 0.001
EID (%)
15.5 ± 5.1
16.3 ± 4.8
0.143
TC (mg/dl)
261.3 ± 28.3
174.3 ± 38.9 < 0.001
(mmol/l)
(6.77 ± 0.73)
(4.51 ± 1.01)
TG (mg/dl)
161.8 ± 66
131.9 ± 50 < 0.001
(mmol/l)
(1.83 ± 0.75)
(1.49 ± 0.57)
LDL-C (mg/dl)
176.8 ± 23.5 92.9 ± 28.1 < 0.001
(mmol/l)
(4.58 ± 0.61)
(2.41 ± 0.73)
HDL-C (mg/dl)
54.7 ± 12.1 54.4 ± 12.4
0.145
(mmol/l)
(1.42 ± 0.31)
(1.41 ± 0.32)
AST (U/l)
23.8 ± 9.1
21.9 ± 5.6
0.068
ALT (U/l)
23.6 ± 12.8
24.1 ± 13.1
0.746
CPK (U/l)
136.8 ± 74
113.4 ± 67
0.427
*Student’s
t
-test,
p
< 0.05.
SD: standard deviation; NTG: post-nitrate; FMD: flow-mediated dilation; EID:
endothelium-independent dilation; AST: aspartate transaminase; ALT: alanine
transaminase; CPK: creatinine phosphokinase; TG: triglycerides; TC: total
cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density
lipoprotein cholesterol.