CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
336
AFRICA
Westernised lifestyle. Hypertension, obesity and diabetes are
highly prevalent in black patients while CVD, which results
from prolonged exposure to cardiovascular risk factors, is
still relatively uncommon. With further progression of the
epidemiological transition, CVD rates in black patients are likely
to rise and may well match or exceed those observed in the other
ethnic groups if cardiovascular risk factors are not addressed
intensively, both on a population and an individual level.
The DYSIS South Africa study identified a group of patients
at high cardiovascular risk, with 73.5% of statin-treated patients
assessed to be at very high risk for CVD. Within this very
high-risk group, despite statin therapy, 85.6% had at least one
lipid abnormality, of which a majority had two or more lipid
abnormalities. The most common lipid abnormality was high
LDL-C levels, which was diagnosed in 60.1% of all very high-
risk patients.
Moreover, for all patients in the study, 50.5% had LDL-C
levels not at goal, which is comparable with the findings from
the recently published CEPHEUS-SA study and the Canadian/
European cohort of the DYSIS study, and below the levels found
in the Middle Eastern cohort (62%).
24,26,30
Not surprisingly, the
metabolic syndrome was present in 67.2% of the sample, since
its components also contribute to elevated CVD risk.
Statistically significant factors associated with high LDL-C
levels included ethnicity, hypertension, DM, and the presence of
coronary and cerebrovascular heart disease. Factors associated
with low HDL-C levels were a high waist circumference, DM
and being treated by a specialist. Elevated TG was associated
with female gender, obesity, DM and peripheral artery disease.
However, the only statistically significant factors independently
associated with the presence of all three lipid abnormalities were
obesity and Asian as well as mixed-ancestry ethnicity.
Based on the current data, it is unclear whether the findings
with regard to ethnicity are biologically or sociologically
determined. Even though this study was conducted exclusively
in the private healthcare sector in South Africa, Asian or mixed-
ancestry ethnicity most likely still correlates partially with
social deprivation, which has been shown to be a risk factor
for cardiovascular disease. Social deprivation may also affect
access to medical care, with less access to specialist care and
a bias towards less aggressive treatment. Studies from other
countries have shown that ethnic minorities or immigrants often
receive less aggressive cardiovascular care,
31
as also observed in
this study, with black patients receiving lower-dose potency of
statins, despite the majority of patients being at high risk.
Socio-economic status has also been associated with statin
adherence,
32
as has ethnicity.
33
In the South African context,
lower socio-economic status would, for instance, often correlate
with membership of a medical scheme option that restricts
lipid-lowering treatment to less-potent (and less-costly) options.
Lower income may also influence the willingness and ability to
pay ‘co-payments’ that are often required to access more potent
lipid-lowering therapy. However, factors such as provider bias,
access to treatment and differential adherence do not completely
explain the observed ethnic differences, as black patients
generally still experience the highest level of socio-economic
deprivation as a legacy of South Africa’s past history.
Lesser goal attainment may also in part be due to differences
in baseline lipids. In the Heart of Soweto study, there were
significant differences in untreated lipid profiles by ethnicity in
patients presenting for cardiovascular care
34
at a tertiary referral
centre. The odds ratio (compared to black patients) for elevated
LDL-C levels in Asian and mixed-ancestry patients was 4.66 and
2.44, respectively. Indian and mixed-ancestry patients also had
higher median TG levels (1.8 and 1.4 mmol/l, respectively) than
black patients (1.1 mmol/l).
In addition to identifying factors that are associated with
dyslipidaemia in statin-treated patients, DYSIS in South
Africa (along with previous DYSIS studies) also highlights the
deficiencies of lipid-lowering therapy in clinical practice. Other
researchers analysing the efficacy of lipid-lowering therapies
have supported this conclusion,
35,36
including another recent study
analysing statin-treated South African patients.
26
Together, these
findings suggest that there is a need to improve upon existing
treatment strategies (e.g. combination of current therapies for
optimal patient efficacy, utilisation of more-potent statins,
improving adherence) while also developing novel therapeutic
approaches.
Combination therapies were evaluated in the Austrian
Cholesterol screening and Treatment (ACT) II study, which
evaluated the effect of lipid-lowering therapies in high-risk,
statin-treated patients with elevated LDL-C levels. Interestingly,
combination therapy consisting of simvastatin and ezetimibe
(used for 73% of patients in the ACT II study) resulted in
40.3% of patients meeting their LDL-C goals, with a decline in
LDL-C levels from a baseline of 31.3% following 12 months of
intensified therapy.
37
High-dose statins are another option to achieve LDL-C targets
in high-risk patients.
38,39
Improving adherence is a challenge that
physicians face every day, and some strategies that have shown
promise include regular phone calls by a practice nurse, regular
review by a community pharmacist and providing a medication
calendar when patients filled their first prescription.
40
There is
likely no single strategy that will work for all patients but studies
show that adherent patients have much better cardiovascular
outcomes than non-adherent patients, although some of the
improvement may also be ascribed to the correlation between
adherence and other healthy behaviours.
41-44
According to a mathematical model of statin use in a
population, increasing statin adherence from 50 to 75% at five
years would prevent more events than lowering the risk threshold
for prescribing statins.
45
Lastly, novel LDL-C-lowering therapies
may be necessary for patients with very high baseline LDL-C
levels, such as is seen in familial hypercholesterolaemia, and
when patients are unable to tolerate adequate doses of potent
statins.
46
In South Africa, the modal statin dose potency prescribed
to patients was 3, which was prescribed to 42.2% of the
individuals. Interestingly, although the very high-risk patients
had a disproportionately high share of the statin prescriptions
with a potency of 4 and 5, they also had a disproportionately
high amount of prescriptions with a potency of 2, and a
disproportionately low share of the prescriptions with a potency
of 6. In addition, although combination therapies may have the
potential to benefit some patients,
37
we found that the use of
combination treatment with lipid-lowering therapies was rare in
South Africa. Only seven patients were co-prescribed statins and
ezetimibe in this study.
DYSIS-South Africa had several limitations, including its
cross-sectional design, which did not permit follow up to assess
