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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 5, September/October 2019
AFRICA
303
R150 per month. The approximate lowering by 50% of LDL-C
concentration is adequate for a large proportion of patients
with FH. There is poor support for additional medication such
as ezetimibe, which may be necessary to improve prevention of
atherosclerotic complications.
A formal diagnosis, including a register of FH, could be used
to support treatment better. It is also important to consider
establishing special clinics at medical schools or larger centres
and that at least one laboratory should be available nationally
to ensure that severe dyslipidaemia is diagnosed correctly.
While newer treatment strategies are often researched in South
Africa, these take time to come to the market. Furthermore, the
newer agents are expensive and may not be supported by state
healthcare and private medical schemes. Nevertheless, cases
where currently available treatment leaves the patient at very high
risk, treatments such as monoclonal antibodies to PCSK9 could
be considered.
Hypercholesterolaemia in the indigenous African population
was discussed in more depth. Dr AAKhine reviewed requests and
results for lipid profiles in South African black patients from in-
and out-patient departments at a tertiary hospital in Gauteng.
20
There were 24 656 requests for 6 348 patients. It appears that
there certainly is a strong awareness of the additional risk for
atherosclerosis from dyslipidaemia in the setting of hypertension
and diabetes, as well as for dyslipidaemia in association with
secondary causes such as nephrotic syndrome. During one year
there were 120 requests from the cardiac intensive care unit;
dyslipidaemia was present in 40% of these patients. One should
bear in mind that there may be a false low level with an acute-
phase response that may mask severe hypercholesterolaemia.
Statins were prescribed in some patients.
The number of patientswithout diabetes andhypertensionwho
had ischaemic heart disease was 19. Severe hypercholesterolaemia
(
>
7 mmol/l) was seen in 299 (4.7%) patients and extreme
hypercholesterolaemia (
>
12 mmol/l) in 30 (0.5%) patients. High
LDL-C levels (
>
5 mmol/l) occurred in 80 (1.3%) patients and
>
10 mmol/l in 19 (0.3%) patients. The diagnosis of FH was
not specifically sought or entertained. The ages ranged from 50
to 84 years and there were five males among the patients with
hypercholestrerolaemia
>
10 mmol/l. It is likely that FH is the
diagnosis in these more extreme cases of hypercholesterolaemia,
but there was also one male with no other explanation for
hypercholesterolaemia of 6.2 mmol/l and ischaemic heart disease
at the age of 37 years.
Dr D van Velden indicated that as an undergraduate in the
early 1970s, he was taught that atherosclerosis was not observed
in the African population. It was mentioned that Isaacsohn
published the finding of atherosclerosis in Johannesburg at
autopsies in the 1970s. Only three African subjects have been
identified with the homozygous FH phenotype. All three were
worked up to an accurate diagnosis: one was a true homozygote
for a six-nucleotide deletion in the LDL receptor gene, one
had autosomal recessive hypercholesterolaemia and one had
sitosterolaemia.
Ongoing research in FH in South Africa is justified, given
the prevalence and severity of this disorder. The Heart and
Stroke Foundation of South Africa and the MRC could not be
represented at the meeting but would be important participants
in future research. Medical schemes serving private as well
as government healthcare should translate the diagnosis and
treatment of FH to improve outcomes. Newer agents that are
under development to lower LDL-C levels may be very expensive
and will have to be carefully evaluated for special cases, in
consultation with expert assessment.
Recommendations
Although not tasked with the provision of guidelines, the
consensus was that:
•
FH should be recognised at the clinical practice level because,
owing to its high prevalence in general and particularly in
certain communities, it will be encountered in primary health-
care. It is treated well with relatively inexpensive medication.
•
Through increased awareness and cascade screening of affect-
ed index cases, it is hoped that primary prevention will be
possible.
•
Treatment with statins, and best with atorvastatin and rosu-
vastatin owing to their greater power, may achieve target
levels set in general, but a proportion of FH patients will need
additional treatment with ezetimibe. An even smaller propor-
tion may require newer treatment strategies.
•
Genetic testing should be supported, and especially for the six
common LDLR mutations or targeted according to inherit-
ance from populations with known mutations. This will
enable precise cascade testing. If no mutation is identified in
the
LDLR
,
APOB
or
PCSK9
genes, then a polygenic profile
may establish this diagnosis and indicate that the cholesterol
test will be the most suitable for detection of FH. Genetic or
trained nurse counsellors are skilled in facilitating cascade
testing and are important in this process.
•
Special clinics and possibly a central laboratory should evalu-
ate patients with severe dyslipidaemias as these patients are
at very high risk and expertise is required for best manage-
ment. A national register should be established based on this
experience.
•
More research is necessary on the local causes of FH and
other severe dyslipidaemias.
•
Advances in treatment need to be translated to this high-risk
population, including novel treatment strategies and even
gene editing.
The FH workshop was based on research supported by the National Research
Foundation (grant number 98069) but the responsibility for opinion, findings,
conclusions or recommendations remains with the investigators. The previous
support of the Medical Research Council is acknowledged for the genetic
work-up as well as the NHLS Research Trust (grant number 004_ 94675).
Profs Dirk Blom and C Vorster are thanked for their contribution to the
discussion, and Drs A Peeters and S Hector for assistance with the investiga-
tion of the polygenic FH family. Dr Nicole van der Merwe is thanked for
assistance with the pedigree.
References
1.
Müller C. Angina pectoris in hereditary xanthomatosis.
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1939;
64
: 675–700.
2.
Motulsky AG. The 1985 Nobel Prize for Physiology or Medicine.
Science
1986;
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: 126–129.
3.
Seftel HC, Baker SG, Sandler MP, Forman MB, Joffe BI, Mendelsohn
D,
et al
. A host of hypercholesterolaemic homozygotes in South Africa.
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: 633–636.