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A healthy lifestyle may not be enough to keep cholesterol levels in check. Certain genetic variations are known to cause some individuals to have severely abnormal levels of cholesterol. — AFP picA healthy lifestyle may not be enough to keep cholesterol levels in check. Certain genetic variations are known to cause some individuals to have severely abnormal levels of cholesterol. — AFP picSINGAPORE, Sept 6 — If a heart-friendly lifestyle and prescribed medication such as statins are not enough to keep cholesterol levels in check, the answer may lie in one’s genes.

Certain genetic variations are known to influence cholesterol levels, causing individuals to often have severely abnormal levels that result in cardiovascular diseases at an earlier age, said cardiologist Peter Ting, co-founder and chief medical officer at Cardiatrics, a doctor-supervised clinical treatment programme to prevent heart disease.

For instance, about one in 250 people may inherit a defective cholesterol-regulating gene from one parent, said Dr Peter Yan, consultant cardiologist at Gleneagles Medical Centre.

This results in a condition known as heterozygous familial hypercholesterolemia (FH), where the body is unable to effectively remove LDL (low-density lipoprotein) cholesterol, or “bad” cholesterol, from the bloodstream. Ideally, LDL cholesterol levels should be kept under 100 mg/dL. An elevated level of this harmful cholesterol is one of the major risks of cardiovascular diseases (heart diseases and stroke) as it collects in the walls of blood vessels over time and can cause blockages.

Dr Yan estimated that over 20,000 Singaporeans could have the milder heterozygous FH, many of whom are undiagnosed.

The inherited condition causes LDL cholesterol levels to be above 190 mg/dL (or a total cholesterol level above 290 mg/dL), and about half of the individuals with the condition will get a heart attack or stroke before the age of 60, he said.

In the more severe and rare homozygous form, the individual inherits two defective copies of the gene, one from each parent, and can have LDL cholesterol levels of over 300 mg/dL (or a total cholesterol level as high as 1,000 mg/dL). In Singapore, high cholesterol affects 17.4 per cent of adults aged 18 to 69.

The most common chronic disease seen in polyclinics, it accounted for 15 per cent of polyclinic attendances last year, said Dr Gerard Leong, medical director of Thomson Cardiology Centre (TCC).

“Most patients are screened for their cholesterol levels in hospitals, and even if they are at very high levels, they are given treatment and not evaluated specifically for underlying FH,” he said.

In Singapore, there is presently no formal registry to track FH numbers. Genetic testing is also uncommon and patients often do not show symptoms until a heart attack occurs. Some individuals may, however, develop signs like tendon xanthomas, which are cholesterol-rich lumps that accumulate in the tendons of the hands, feet and heels, said Dr Leong.

According to him, early intervention to curb abnormally high cholesterol levels can lower the risk of premature coronary artery disease.

Individuals with a family history of FH, cardiovascular disease at an early age (before 50 and 60 years old in male and female relatives, respectively) or other risk factors for coronary artery disease, such as smoking, diabetes, hypertension, should have their cholesterol levels screened annually from the age of 18, he said.

When statins don’t work

Patients who develop significant side effects with conventional medications are another group who may find it hard to control their cholesterol levels.

For instance, while statins are one of the most effective medications to treat high cholesterol, it is estimated that up to 15 per cent of patients may not tolerate them, said Dr Ting.

“(Intolerance) usually manifests as muscle aches or abnormal liver function test results that are serious enough to require the patient to stop the medication,” he said.

An alternative treatment option known as PCSK9 inhibitors is now available in Singapore. This new class of drugs targets and inactivates a specific protein which affects the lifespan of “cholesterol clearing” receptors on liver cells. These receptors then stay on liver cells for longer and clear more harmful LDL cholesterol from the bloodstream and body.

Dr Leong said it can reduce LDL cholesterol levels by 60 to 70 per cent, and significantly reduce stroke or heart attack risk.

However, PCSK9 inhibitors are much costlier than current standard cholesterol-lowering medications. For example, generic statins and brand-name statins may cost about S$20 (RM62) and S$100 per month, respectively, while PCSK9 inhibitors cost about S$800 per month, said Dr Ting.

Lifestyle modification should remain the first line of treatment for everyone with high cholesterol, said Dr Ting.

A new study led by Harvard Medical School scientists at Massachusetts General Hospital, has shown that even among those who cannot escape the genetic risk, leading a healthy lifestyle can cut the probability of a heart attack by half. The report was published in the New England Journal of Medicine in December last year.

“LDL cholesterol can be reduced effectively through lifestyle modification but it can be difficult to achieve this on your own. Studies have shown that guidance and monitoring by a physician and health team in the context of a structured prevention programme can reduce cholesterol by 20 to 30 per cent,” said Dr Ting. — TODAY

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