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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 5, September/October 2019
AFRICA
247
Familial hypercholesterolaemia and its management in
South Africa
AD Marais
This issue of the
Cardiovascular Journal of Africa
has published
two articles relevant to severe dyslipidaemias. A new therapeutic
agent under review by the South African Health Products
Regulatory Agency (SAHPRA) has already been used in
pharmaceutical trials
1
in South Africa, a country renowned
for founder effects in familial hypercholesterolaemia (FH) in
the Afrikaner, Jewish and Indian communities (page 279).
The workshop on FH provides an update and important local
information (page 297).
2
Twenty years after theWorldHealthOrganisationpublication,
3
renewed efforts are being made internationally to recognise,
detect and treat FH. The FH Foundation in the USA arranged
a global call-to-action summit meeting last year.
4
The high risk
of atherosclerosis, successful treatment and the high prevalence
in all populations are compelling reasons for the recognition of
FH worldwide, as well as in our healthcare system, despite the
current strains.
Atherosclerosis incubates asymptomatically until an abrupt
clinical manifestation at thrombosis, most prominently in the
coronary arteries. In the Cape Town experience, the mean age
for myocardial infarction in men is 45 years,
5
but has been
documented at 23 years. While atherosclerosis is multifactorial
in its pathogenesis and its risk is best assessed by taking into
account several risk factors for most patients, in FH the process
is almost entirely driven by the elevated low-density lipoprotein
cholesterol (LDL-C) concentration.
At the time that screening for treatment of
hypercholesterolaemia was advised for higher-risk cases in the
Sheffield table,
6
testing for hypercholesterolaemia to detect FH
at a young age was highlighted owing to its high risk. Persons
with FH are excluded from risk calculations that guide treatment
in the South African guideline for treatment of dyslipidaemia.
7
LDL hypercholesterolaemia exceeding a concentration of
5 mmol/l, equivalent to a total hypercholesterolaemia exceeding
7.5 mmol/l, is suggestive of FH and requires intervention
8
owing
to the exponential function of risk. In FH, the triglyceride
concentration is generally normal. Common secondary causes
for hypercholesterolaemia that require exclusion are nephrotic
syndrome and hypothyroidism. LDL hypercholesterolaemia of >
5 mmol/l together with an Achilles tendon xanthoma clinches the
diagnosis. Tendon xanthomata are useful clinical signs that set in
after the second decade but are often overlooked.
In FH, impaired clearance of LDL from the circulation into
the liver relates to dysfunction of the LDL receptor, poor binding
to the receptor of apoliprotein B in LDL, and increased LDL
receptor degradation by proprotein convertase subtilisin/kexin
type 9 (PCSK9). These disorders are autosomal dominantly
inherited. Rarely, recessive disorders cause a FH phenotype and
in some cases FH may be polygenic.
9
There is a gradation of
severity in FH according to the functional impact of mutations.
8
Fortunately, the severe homozygous FH phenotype is rare but
must be considered when both parents have FH.
The target concentration for LDL-C concentration in FH
subjects may be similar to that for other cases of primary
prevention of atherosclerosis, i.e. 3 mmol/l when detected early.
But for those at higher risk at older age, the recommended
LDL-C concentration is at least below 2.5 mmol/l.
7
Because
the lower border of LDL cholesterol concentration in FH is
5 mmol/l, prescription of maximal doses of atorvastatin or
rosuvastatin should achieve the target concentration. Less than
10 and 50% of heterozygous FH, without and with heart disease,
respectively, will achieve target on such treatment. Additional
ezetimibe will achieve target in 54 and 93%, respectively.
10
A
number of more severe cases will require the additional lowering
that PCSK9-neutralising antibodies provide.
Based on the prevalence of FH at one in 500 persons, there
are more than 1.5 million individuals with FH in sub-Saharan
Africa and about 250 000 in South Africa; of whom the majority
will be in the black population. Africa is lagging behind in the
detection and treatment of FH. Despite early research in FH in
South Africa, translation of the diagnosis and treatment of FH
into clinical practice has been disappointing in both the public
and private healthcare sectors. The discipline of lipidology, or
vascular medicine in some countries, has not developed in South
Africa. Not only are there few doctors with relevant clinical
skills but also the scope of diagnostic investigation for severe
dyslipidaemia is limited.
In most cases management is not difficult. Maximal doses
of the more powerful statins will suit a large proportion of
FH patients, with a majority achieving target with the addition
of ezetimibe, with dramatic improvement in the quality and
duration of life.
Keywords:
familial hypercholesterolaemia, national health insur-
ance, statins, ezetimibe, PCSK9 neutralising agents
Cardiovasc J Afr
2019;
30
: 247–248
www.cvja.co.zaDOI: 10.5830/CVJA-2019-054
Chemical Pathology, Health Sciences, University of Cape
Town, Observatory, South Africa
AD Marais, FCPSA,
david.marais@uct.ac.zaEditorial