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Cardiovascular diseases, which are diseases involving the heart and blood vessels, is a leading cause of death in Singapore, accounting for more than 30% of all deaths in 20221. With Singapore’s rapidly ageing population, the incidence of AMI and Stroke is expected to rise. The Singapore Myocardial Infarction Registry showed the number of heart attacks increased from 8,014 in 2011 to 12,403 in 20212. Similarly, the Singapore Stroke Registry showed that the number of strokes increased from 6,143 episodes in 2011 to 9,680 episodes in 20212.
High levels of LDL cholesterol (LDL-C) are a main culprit for cardiovascular events, and lowering these levels can reduce the risk of heart attack and stroke.
Elevated LDL-C plays a key role in the formation of arterial plaques, i.e. deposits in the vessels. The arteries are narrowed by these plaques, which leads to atherosclerosis, also known colloquially as hardening of the arteries. As the disease progresses, the transport of oxygen through the blood becomes restricted. In the worst case, the vessel is completely blocked. The consequences can be a heart attack, stroke or peripheral arterial disease - depending on which region of the body the blocked vessel is located.
Patients who have high LDL-C levels may have an existing hereditary disease - familial hypercholesterolemia (FH).
FH is an example of a disease that is caused by a mutation of a gene. The change usually affects the gene for the important LDL-C receptors. Normally, these receptors help the liver remove LDL cholesterol from the blood, thereby lowering blood cholesterol levels. However, their function is disrupted due to a mutation.
Cholesterol breakdown is influenced by the PCSK9 protein. This protein binds the LDL-C receptors, which leads to their breakdown in the liver cell. This means that the receptors for the absorption of LDL cholesterol are no longer available. If the activity of PCSK9 is too high and that of the LDL-C receptors is relatively weak, cholesterol levels in the blood increase, which leads to an increased cardiovascular risk.
With the discovery of this gene mutation and an understanding of the biology of familial hypercholesterolemia, our scientists identified a suitable antibody against the protein PCSK9 that can “neutralize” the effect of the protein and thereby lead to a reduction in LDL-C levels.