CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 5, September/October 2011
AFRICA
235
well as in the US
14,15
among individuals taking LLDs have shown
that a relatively small proportion of patients achieve their target
lipid levels. This is particularly the case when CVD risk is high
and the lipid targets are set lower.
The CEntralised Pan-South African survey on tHE
Undertreatment of hypercholeSterolaemia (CEPHEUS SA) was
initiated to detect and quantify the degree of under-treatment of
hypercholesterolaemia in South Africa, and to identify positive
and negative determinants for being at LDL-C targets. This non-
interventional study also investigated patient and physician char-
acteristics as well as the attitudes of these two groups towards the
management of hypercholesterolaemia.
Methods
This non-interventional study was conducted between November
2009 and April 2010 in 69 study centres (both private and public
sectors) in South Africa. Male and female patients aged 18 years
or older who had been receiving LLDs for at least three months
(without dose adjustments for at least six weeks) were eligible.
Patients who came for their regular scheduled visit to the doctor/
clinic were consecutively invited to participate in the survey.
Patients who agreed to participate provided written informed
consent. There were no exclusion criteria apart from unwilling-
ness or inability to provide informed consent.
The final protocol was approved by the appropriate ethics
committees as well as the South African Medicine’s Control
Council. The survey was performed in accordance with the
Declaration of Helsinki and the International Conference on
Harmonisation of Good Clinical Practice guidelines.
CEPHEUS SA was a single-visit study. Before any patients
were recruited, each investigator completed a questionnaire
on his/her experience and perception of the management of
hypercholesterolaemia, as seen in his/her patients. The investi-
gators were asked to indicate their general attitude towards the
diagnosis of hypercholesterolaemia, their perception of existing
guidelines and goals, as well as their knowledge on the treatment
of dyslipidaemia.
Before being assessed by the investigator, patients completed
a questionnaire about their awareness and perceptions of hyper-
cholesterolaemia, their current LLD regimen, and their compli-
ance with the treatment.
For each patient, the investigator completed a patient record
form, which included information on the patient’s demographics,
current LLD treatment, and reason for initiating LLD treatment.
The investigator also recorded the presence of known cardio-
vascular risk factors such as smoking, diabetes, family history
of premature CHD (defined as definite myocardial infarction
or sudden death before 55 years of age in father or other male
first-degree relative, or before 65 years of age in mother or other
female first-degree relative),
5,7
arterial hypertension (defined
as blood pressure
≥
140/
≥
90 mmHg or current use of antihy-
pertensive medication), and cardiovascular medical history.
Investigators were specifically asked to identify patients in
whom the primary reason for starting LLD was a diagnosis of
familial hypercholesterolaemia.
Physical examination by the investigator was limited to meas-
urement of height, weight, waist circumference and blood pres-
sure. A fasting blood sample was drawn to evaluate the serum
lipid profile [including measurement of apolipoprotein (Apo) AI
and Apo B] and glucose level. Blood samples were collected in
three tubes [5 ml in a gel tube, 2 ml in a fluoride tube and 2 ml in
an ethylenediaminetetra-acetic acid (EDTA) tube] using materi-
als provided by the central laboratory. Laboratory analyses were
performed at Quintiles Laboratories, South Africa. Glucose,
total cholesterol, HDL-C and triglyceride levels were analysed
by the Roche BMD method. LDL-C (direct) was quantified by
colorimetry, and Apo AI and Apo B were evaluated by the Roche
Tinaquant method.
Normal weight was defined as a body mass index (BMI)
<
25
kg/m
2
, overweight as a BMI
>
25 and
<
30 kg/m
2
, and obesity
as a BMI
>
30 kg/m
2
. Metabolic syndrome was defined as the
presence of three or more of the following:
16,17
abdominal obesity
with a waist circumference of
>
94 cm for men or
>
80 cm for
women; plasma triglyceride levels
≥
1.7 mmol/l; a high-density
lipoprotein cholesterol (HDL-C)
<
1.0 mmol/l for men or
<
1.3
mmol/l for women; blood pressure
≥
130/
≥
85 mmHg; and a
fasting glucose level
≥
5.6 mmol/l.
Study endpoints
The primary endpoint was the percentage of patients who
achieved the LDL-C goals according to the NCEP ATP III/2004
updated NCEP ATP III guidelines,
6
or the Fourth JETF
7
/South
African guidelines which were current at the time the CEPHEUS
SA study was conducted in South Africa (Table 1).
Achievement of the LDL-C goal was also evaluated according
to (1) the presence or absence of the metabolic syndrome; (2)
primary versus secondary prevention; (3) demographic variables,
(4) CVD risk factors, (5) class of lipid-lowering agent and (6)
patient and physician determinants. In addition, the percentage
of patients achieving the non-HDL-C goal of
<
3.36 mmol/l
according to the NCEP ATP III/2004 updated NCEP ATP III
guidelines was also evaluated in patients with fasting triglycer-
ides
>
2.26 mmol/l.
Statistical analysis
Sample size calculations were based on the need to ensure that
the proportion of patients reporting on the primary and secondary
endpoints could be estimated with sufficient precision, overall
and on a by-sub-population basis. Hence, sample size determina-
tion was not based on test power considerations, but on the confi-
dence limit approach to ensure adequate precision estimates.
For a precision within
±
three percentage points, the length of
the two-sided 95% confidence interval (CI) should not exceed
three percentage points in each direction from the point estimate.
For sample size calculations, and in accordance with standard
practice, the proportion of patients achieving the LDL-C goal was
assumed to be 50%, as this proportion was unknown. Based on
thesecalculations,theminimumsamplesizeofabout1000patients
TABLE 1 LDL-C GOALACHIEVEMENT TARGETS
Risk category
NCEP ATP III/
2004 NCEP ATP III European
South
African
High risk
Current goal (mmol/l)
<
2.6
<
2.5
<
2.5
Optional goal (mmol/l)
<
1.8
<
2.0
–
Medium/low risk
Current goal (mmol/l)
<
3.4
<
3.0
<
3.0
