Unmet challenges in treating high blood cholesterol levels
An increasing proportion of the Malaysian population has high blood cholesterol levels or hypercholesterolaemia.
The National Health and Morbidity Survey (NHMS) 2011 showed about 33 percent of Malaysians aged above 18 had hypercholesterolaemia; this figure increased to about 47 percent as documented in NHMS 2015. This statistic may further increase in the next NHMS most likely in 2020, said Datuk Dr Ahmad Khairuddin Mohamed Yusof, consultant cardiologist, National Heart Institute.
“There is a significant number of our population in Malaysia which has high cholesterol levels in their blood.”
The prevalence of hypercholesterolaemia generally increased with age—from 22 percent in 18-19-year-olds, more than 50 percent in 40-44-year-olds and about 68 percent in 55-59-year-olds. [NHMS 2015. Available at: http://iku.moh.gov.my/images/IKU/Document/REPORT/nhmsreport2015vol2.pdf]
Hypercholesterolaemia and endothelial dysfunction cause narrowing of blood vessels and result in cardiovascular disease (CVD). Atherosclerosis is accelerated in patients with type 2 diabetes due to hyperglycaemia, insulin resistance, inflammation and diabetic dyslipidaemia. [Circulation 2001;104(3):365–372; Can J Diabetes 2013;37(5):345–350]
Malaysians are developing heart disease at a younger age (58 years old) compared with other countries eg, Thailand (65 years), China (63 years) and western countries (GRACE* Registry-66 years and Canada-68 years). [MOH. Primary and secondary prevention of cardiovascular disease. Available at: www.moh.gov.my, Malaysian statistics on medicines 2008: Use of lipid modifying drugs. Available at: www.crc.gov.my/nhsi/wp-content/uploads/publications/msom2008/chapter10.pdf] Also, Malaysia has one of the highest prevalence rates of CVD among Asian countries. [J Pharm Bioallied Sci 2017;9(2):80–87]
However, the use of statins in Malaysia is much lower compared with the developed countries. As a result, only half of patients with high CV risk factors achieve target LDL-C levels. [Malaysian statistics on medicines 2008: Use of lipid modifying drugs. Available at: www.crc.gov.my/nhsi/wp-content/uploads/publications/msom2008/chapter10.pdf, Southeast Asian J Trop Med Public Health 2011;42(2):388–394]
While intensive statin therapy provides additional CV risk reduction, residual CV risk remains. [N Engl J Med 2005;352(14):1425–1435] These patients should be treated and include those with diabetes and underlying hypertension and high cholesterol levels, said Ahmad.
Another challenge is treating patients with familial hypercholesterolaemia (FH), which is a genetic disorder that causes high levels of LDL-C and an increased risk of premature CVD. [Eur Heart J 2016;37(17):1398–1405, The FH Foundation. Available at: https://thefhfoundation.org/about-fh/what-is-fh] It is important to lower cholesterol levels at a young age and reset the vascular age clock. It is possible now because newer lipid-lowering agents are available, said Ahmad.
One such lipid-lowering agent is evolocumab, which is of a novel class of treatment that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Evolocumab is a monoclonal antibody targeted to the PCSK9 protein which is involved in the LDL receptor expression, said Dr Choo Gim Hooi, a consultant cardiologist. PCSK9 is produced mainly by the liver and influences the uptake of LDL-C from the blood circulation. [Hum Mutat 2009;30(4):520–529, Proc Natl Acad Sci USA 2003;100(3):928–933, J Lipid Res 2009;50(Suppl):S172–S177]
Evolocumab results in up to 77 percent additional LDL-C lowering in patients already on statin therapy and up to 60 percent LDL-C reduction in patients with FH. It is safe with minor side effects and administered via 2-weekly or monthly subcutaneous injections.
Choo pointed out that there are two sources of cholesterol in the human body. Up to 80 percent of cholesterol is produced in the liver compared with 20 percent from the diet. So, healthy lifestyle alone is inadequate to lower LDL-C to target levels; lipid-lowering therapy is still needed, said Choo.
Ahmad and Choo were speaking at the launch of evolocumab (Repatha®, Amgen).