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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 5, September/October 2019
AFRICA
297
Familial hypercholesterolaemia workshop for leveraging
point-of-care testing and personalised medicine in
association with the Lipid and Atherosclerosis Society of
Southern Africa
AD Marais, MJ Kotze, FJ Raal, AA Khine, PJ Talmud, SE Humphries
Abstract
Familial hypercholesterolaemia (FH) is a common autosomal
dominantly inherited disorder in which impaired clearance of
plasma low-density lipoprotein cholesterol causes premature
atherosclerotic vascular disease and tendon xanthomata. This
workshop aimed to consolidate information on the diagnosis
and management of FH in South Africa. The genetic causes
include mutations in the LDL receptor, apolipoprotein B100
and proprotein convertase subtilisin/kexin type 9 (PCSK9).
Additionally, the concatenation of multiple gene variants can
result in polygenic FH.
Therapeutic measures include a healthy lifestyle, statins
and cholesterol-absorption inhibitors that will achieve
control of the dyslipidaemia in the majority of cases. The
recently introduced monoclonal antibodies to PCSK9 can
improve achievement of target concentration in severe cases.
FH is present in all sectors of the South African popula-
tion but there is sparse documentation in the indigenous
African populations. FH should be actively sought, diag-
nosed and treated with judicious pharmacotherapy and
screening of relatives.
Keywords:
familial hypercholesterolaemia, pharmacotherapy,
genetic testing, founder effect
Submitted 20/8/19, accepted 12/9/19
Cardiovasc J Afr
2019;
30
: 297–304
www.cvja.co.zaDOI: 10.5830/CVJA-2019-055
This article summarises the presentations and discussion at
a workshop on familial hypercholesterolaemia (FH) at the
P5 Africa conference for leveraging point-of-care testing and
personalised medicine to advance healthcare, held in Newlands,
Cape Town, on 24 March 2016. The purpose of this workshop
was to summarise the experience in South Africa and to provide
an update on recent developments in FH in general, and in
particular, the additional availability of monoclonal antibodies
that neutralise proprotein convertase subtilisin/kexin type 9
(PCSK9). The importance of recognising and treating FH and
what needs to be done in the future was discussed. Only the most
pertinent references are supplied.
FH was recognised as a clinical entity with autosomal
dominant inheritance in 1938 byMüller.
1
The underlying cause for
the severe elevation of plasma low-density lipoprotein cholesterol
(LDL-C) was unravelled through studying homozygotes for
FH by Brown and Goldstein whose Nobel Prize celebration
2
indicated that the error is at the LDL receptor. The underlying
mechanism is therefore defective clearance of LDL-C.
The high prevalence of FH was recognised through the host
of homozygous hypercholesterolaemia patients of Afrikaner
(mostly European) ancestry in Johannesburg,
3
and research in
South Africa exposed the underlying genetic mutations.
4
The
lifelong severe LDL hypercholesterolaemia of heterozygous FH
confers premature heart disease: typically in the middle of the
fifth decade of life for men,
5
and much earlier in homozygous
FH.
2
Effective treatment became available with the advent of
hydroxy-methylglutaryl coenzyme A reductase inhibitors, now
referred to as statins, and the improvement in the prognosis is
evident, with an overall risk reduction of 76% on statins before
the advent of high doses.
6
While bile acid sequestrants have been
available since the middle of the previous century, ezetimibe
7
has
replaced these as second choice in FH because the newer agent
is better tolerated.
Chemical Pathology, Health Sciences Faculty, University of
Cape Town, Observatory, South Africa
AD Marais, FCPSA,
david.marais@uct.ac.zaDivision of Chemical Pathology, Department of Pathology,
Faculty of Medicine and Health Sciences, Stellenbosch
University; National Health Laboratory Service, Tygerberg
Hospital, Tygerberg, South Africa
MJ Kotze, MD
AA Khine, MD
Department of Medicine, Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, South
Africa
FJ Raal, MD
Centre for Cardiovascular Genetics, Institute of
Cardiovascular Science, University College London,
London, United Kingdom
PJ Talmud, MD
SE Humphries, MD
Workshop at P5 Africa conference