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Hatter Lipid Research Group

Lipidology services and research at UCT date back more than 5 decades and have historically involved multiple departments including Chemical Pathology, Medical Biochemistry and Medicine. Lipidology has grown in the last few years and is now spread over two departments. The Department of Medicine and the Hatter Institute house the Division of Lipidology (Head: Associate Professor D. Blom) while the Lipid Laboratory is located within the Division of Chemical Pathology (Head: Professor A.D. Marais) in the Department of Clinical Laboratory Sciences. The two components of Lipidology co-operate very closely in the investigation and management of patients.

The Division of Lipidology provides clinical services mainly on an outpatient basis but does also offer a consultation service for inpatients with severe disorders of lipoprotein metabolism. Additionally, the Division of Lipidology is engaged in clinical research including research on novel lipid-lowering and anti-atherosclerotic agents. The division also provides an ultrasonographic service for the determination of carotid intima media thickness (IMT). The division is actively involved in developing local guidelines and policies. The division is run from the Cape Heart Centre, formed in 1997 by uniting the Ischaemic Heart Disease unit, Cardiovascular Research unit in Cardiothoracic Surgery and more recently, the Hatter Institute, to promote cardiovascular research at this faculty.

The Lipid Laboratory provides specialized investigations for dyslipidaemia that are generally not available elsewhere in the country. Routine investigations include determination of lipoprotein particle size by non-denaturing gradient gel electrophoresis, ultracentrifugation and analysis of VLDL composition for the diagnosis of dysbetalipoproteinaemia and genotyping to detect mutations in the LDL-receptor, apolipoproteinE and lipoprotein lipase. More specialized investigations such as measurement of 7-dehydrocholesterol for the diagnosis of Smith-Lemli-Opitz syndrome, measurement of plant sterols for the diagnosis of sitosterolaemia, cell culture and analysis of other genes are performed as required. The laboratory has recently acquired novel equipment (HPLC with time of flight mass spectroscopy and Direct Analysis in Real Time[DART]) that will expand its diagnostic capabilities considerably.

TEACHING

Undergraduate teaching includes tutorials and lectures to final year and fourth year medicine students. Postgraduate teaching activities include clinical, laboratory and research meetings. A clinical meeting is held on Tuesdays from 12h30 to 13h30 and utilises the preceding clinic for teaching: discussions centre around patients who were seen and topics of clinical interest. A laboratory meeting is held on Fridays from 12h00 to 13h00 to evaluate the diagnostic tests that were performed in the laboratory. This exposes the postgraduate students to a variety of electrophoretic, ultracentrifugation and some genetic investigations as well as some chromatography. A Lipid and Atherosclerosis Research Forum (LARF) is held every Thursday at 12h00 to 13h00 to discuss a wide range of issues in lipidology, encompassing epidemiology, general medicine, cardiology, pharmacology, pathology, chemistry, and biochemistry. A review of recent scientific literature is also included in this programme. The division also regularly provides continuing medical education activities for general practitioners and specialists.

RESEARCH

The Division of Lipidology has been active in the study of strategies to control dyslipidaemia and the associated vascular disease. There is a strong emphasis on participating in clinical trials in the development of lipid modifying drugs in moderate and severe dyslipidaemia. Our unit’s experience relates to virtually all statins from their earliest trials, fibrates, ezetimibe, other cholesterol absorption inhibitors (AVE5530), nutraceuticals, cholesterol ester transfer protein inhibitors (torcetrapib), acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, squalene synthase inhibitors (lapaquistat), extended release niacin with laropiprant, microsomal triglyceride transfer protein inhibitors (lomitapide), antisense oligonucleotides (mipomersen), thyroid hormone receptor agonists and monoclonal antibodies to PSCK9. More recently the division has also participated in diabetes trials with cardiovascular endpoints (rosiglitazone, dilaglutide). Clinical research that leads to the identification of specific, severe disorders of lipoprotein metabolism or the characterisation of unusual disorders, contributes to the understanding of the prevalence and causes of these disorders in the region we serve. The unit also contributes lipid expertise to the study of metabolic alterations associated with antiretroviral therapy.

Laboratory research includes the description of dyslipidaemia by novel techniques including non-denaturing gradient gel electrophoresis and a modified Chugaev reaction. Clinical laboratory research has included the investigation of dyslipidaemia by stable isotope turnover studies in collaborations with international units. Current research includes investigation of LDL-receptor mutations, lipoprotein lipase mutations, apolipoproteinE mutations, endothelial lipase mutations, Smith-Lemli-Opitz syndrome, PCSK9 (in collaboration with Professor Gilles Lambert) and hypobetalipoproteinaemia. Other research interests include lipid peroxidation in edible oils and the anti-oxidant activities of foodstuffs including wine. The laboratory is also collaborating with the Department of Archaeology in the determination of the nutritional composition of the diet that was likely consumed by early hominids.

Current Clinical Trials in Lipidology

Compound Indication
Dulaglutide CV risk reduction in diabetes
Pemafibrate CV risk reduction in diabetes
Alirocumab Severe hypercholesterolaemia
Evolocumab Severe hypercholesterolaemia
Evanicumab Extreme hypercholesterolaemia
Bempedoic acid Statin intolerance
Epanova CV risk reduction with atherogenic dyslipidaemia
Volanesorsen Familial chylomicronaemia syndrome
Inclisiran  Familial Hypercholesterolaemia