Familial Hypercholesterolaemia (FH) in Singapore: Diagnosis, Risk, and Treatment
- Dr Chan Po Fun
- 3 days ago
- 8 min read
Dr Chan Po Fun [MBBS, MRCP, FRCP (UK), FAMS (Cardiology)] is a consultant cardiologist in Singapore with a focused practice in lipid management and cardiovascular risk reduction.
Familial Hypercholesterolaemia: When High Cholesterol Is in Your Genes
Most people with high cholesterol are told to improve their diet, exercise more, and take a statin. For many, this is the right approach.
But for patients with familial hypercholesterolaemia (FH), the situation is different. Their cholesterol is high because of their genes, not their lifestyle. And for many, statins alone are not enough to reach their LDL target.
FH is one of the most common inherited cardiovascular conditions, yet it is significantly underdiagnosed in Singapore. Most patients with FH do not know they have it.
In short: Familial hypercholesterolaemia is an inherited condition that causes very high LDL cholesterol from birth. Without treatment, it leads to premature coronary artery disease. Early diagnosis and appropriate treatment significantly reduce this risk. This article explains what FH is, how it is diagnosed, who is at risk, and how it is managed.
In Singapore, FH affects approximately 1 in 140 people — yet most cases remain undiagnosed.
What Is Familial Hypercholesterolaemia?
Familial hypercholesterolaemia is a genetic condition that affects the liver's ability to remove LDL cholesterol from the blood.
In a healthy liver, LDL receptors act as docking stations that capture LDL particles circulating in the blood and clear them. In patients with FH, a mutation in one of several genes, most commonly the LDLR gene, which encodes the LDL receptor, means these receptors are either absent, reduced, or not functioning correctly.
The result is that LDL cholesterol accumulates in the blood from birth, at levels far higher than a normal diet or lifestyle would produce.
Heterozygous FH (one mutated copy of the gene, inherited from one parent) is the more common form, affecting approximately 1 in 200-300 people. In Singapore specifically, the estimated prevalence is 1 in 140, significantly higher than the global average, making FH more common here than in most countries. Untreated, these patients typically have LDL cholesterol levels of 5 to 10 mmol/L.
Homozygous FH (two mutated copies, one from each parent) is much rarer, affecting approximately 1 in 250,000 to 300,000, and results in even more severely elevated LDL, often above 13 mmol/L. Without aggressive treatment, homozygous FH can cause cardiovascular events in childhood.
Why FH Is a Serious Condition
The cardiovascular risk from FH is not simply about one elevated reading. It is the result of decades of exposure to very high LDL cholesterol, beginning in childhood or even earlier.
A patient with untreated heterozygous FH may accumulate 20 to 30 years of atherosclerotic plaque burden before reaching middle age. This is why FH is associated with:
Heart attack at a significantly younger age than the general population, often in the 40s or 50s in men, and slightly later in women
Premature coronary artery disease in first-degree relatives
Tendon xanthomas: yellowish cholesterol deposits, typically in the Achilles tendon or over the knuckles (seen in some but not all patients)
Corneal arcus: a grey-white arc around the edge of the cornea, which in younger patients can suggest elevated lipids
The risk is substantially modified by treatment. Patients with FH who are identified early and treated appropriately have significantly better outcomes. The key is diagnosis.
How Common Is FH in Singapore?
Globally, FH affects approximately 1 in 200 to 300 people. In Singapore specifically, the estimated prevalence is 1 in 140, significantly higher than the global average. In a country of 5.5 million people, this means an estimated 39,000 Singaporeans may have FH, the majority of whom remain undiagnosed.
FH is significantly underdiagnosed. Globally, only about 10% of cases are estimated to be identified. In Singapore, awareness among both patients and non-specialist clinicians remains limited.
This means that many patients with FH are either untreated, or treated as if they have ordinary elevated cholesterol, without the more intensive approach their genetic risk requires.
How Is FH Diagnosed?
FH is a clinical diagnosis, based on a combination of:
LDL cholesterol level — particularly if very high (above 5 mmol/L in adults, or above 4 mmol/L in children)
Personal and family history — particularly early cardiovascular disease in first-degree relatives (father or brother before age 55, mother or sister before age 65)
Physical examination — presence of tendon xanthomas or corneal arcus in younger patients
Genetic testing — confirms the diagnosis and identifies family members at risk
Several scoring systems exist to standardise FH diagnosis in clinical practice.
The Dutch Lipid Clinic Network (DLCN) criteria are widely used internationally and in Singapore, assigning points across family history, clinical history, physical examination, and LDL level. A score above 8 suggests definite FH. A score of 6 to 8 suggests probable FH. A score of 3 to 5 suggests possible FH.
Genetic testing, while not always necessary for clinical management, is particularly useful for cascade screening, identifying other family members who may be affected.
Cascade Screening: Why Family Members Should Be Tested
FH follows an autosomal dominant inheritance pattern. This means that first-degree relatives (parents, siblings, and children) of a patient with confirmed FH each have a 50% chance of carrying the same mutation.
Cascade screening , systematically testing family members of an identified patient, is one of the most cost-effective strategies for reducing FH-related cardiovascular events. Finding and treating an affected relative early can prevent a heart attack that might otherwise occur in their 40s or 50s.
If you are diagnosed with FH, I recommend discussing testing with your siblings and adult children. Cholesterol testing in children with a family history of FH can be considered from age 5 to 10.
Why Diet and Lifestyle Are Not Enough for FH
This is a point that causes significant frustration for FH patients who are told to "try diet changes first."
Because FH is a genetic defect in LDL receptor function, it is not meaningfully responsive to dietary change. A patient with FH who follows an excellent diet will still have LDL cholesterol several times above normal. Lifestyle modification is still recommended, for overall cardiovascular health, but it is not a substitute for medication in FH.
Similarly, starting a low-intensity statin and taking a wait-and-see approach is not appropriate for most FH patients. The LDL has been elevated since birth. The clock has already been running.
How FH Is Treated
Treatment for FH is more intensive than for ordinary high cholesterol, because the LDL levels are higher and the risk is greater.
High-intensity statin therapy
The first-line treatment is high-intensity statin therapy, typically rosuvastatin 20 to 40 mg or atorvastatin 40 to 80 mg daily. These can reduce LDL by 50 to 60% from baseline. For many heterozygous FH patients, this is a meaningful reduction, but it may not be enough to reach the recommended LDL target.
Ezetimibe
Ezetimibe is added to further reduce LDL by a further 15 to 20%. The combination of high-intensity statin plus ezetimibe is now standard practice for FH management, and is recommended before considering injectable therapies.
For patients who remain above their LDL target despite maximally tolerated statin and ezetimibe , which is common in FH, PCSK9 inhibitors are guideline-supported and highly effective. They can reduce LDL by a further 50 to 60% on top of existing therapy.
FH is one of the clearest indications for PCSK9 inhibitor therapy in international and Singapore guidelines.
The newer siRNA-based injectable therapy, given twice yearly after the initial doses, is also an option for FH patients who require further LDL reduction or who prefer a less frequent injection schedule.
For patients with FH and no established cardiovascular disease, the treatment target is LDL below 2.6 mmol/L (some guidelines suggest below 1.8 mmol/L given lifetime risk). For patients with FH and established cardiovascular disease, or very high-risk FH, the target is LDL below 1.4 mmol/L.
These targets are substantially lower than those required for ordinary cholesterol management, reflecting the higher lifetime risk of FH.
What to Expect at a Consultation for FH
If FH is suspected, a specialist consultation will typically involve:
A detailed personal and family history, focusing on age of cardiovascular events in first-degree relatives
A review of all previous cholesterol results and their trend over time
Physical examination for clinical signs such as tendon xanthomas
LDL-C measurement and risk stratification using DLCN or similar criteria
Lp(a) testing — elevated Lp(a) is more common in FH patients and adds further risk
Discussion of cascade screening for family members
A personalised treatment plan based on FH severity and overall cardiovascular risk
The Bottom Line
Familial hypercholesterolaemia is a common, underdiagnosed, and highly treatable condition. Left untreated, it leads to premature heart disease. Identified early and managed appropriately, the risk can be substantially reduced.
If you have very high LDL cholesterol, a strong family history of early heart disease, or have been told your cholesterol is "genetic", a formal FH assessment is worth pursuing. A single consultation can clarify your diagnosis, your risk, and your treatment options.
No referral required. Consultations available at Gleneagles Hospital and Mount Alvernia Hospital.
About Dr Chan Po Fun
Dr Chan Po Fun is a consultant cardiologist in Singapore with a focused practice in lipid management, including familial hypercholesterolaemia diagnosis and treatment, Lp(a) assessment, statin intolerance, and advanced injectable lipid therapies.
She provides structured, personalised assessments for patients with suspected or confirmed FH, including guidance on cascade screening for family members.
Frequently Asked Questions
Can I have familial hypercholesterolaemia if I am slim and eat well?
Yes. FH is a genetic condition that affects LDL receptor function in the liver. It is not caused by diet, weight, or lifestyle, and it does not resolve with lifestyle changes. Many patients with FH are surprised by their high LDL because they lead healthy lives. This is precisely why FH is underdiagnosed.
How do I know if my high cholesterol is genetic or lifestyle-related?
Several features suggest a genetic cause: very high LDL (above 5 mmol/L in adults), family history of early heart disease or very high cholesterol, LDL that remains high despite good diet and exercise, and the absence of other causes such as diabetes or hypothyroidism. A specialist assessment using clinical criteria such as the Dutch Lipid Clinic Network score can help clarify the diagnosis.
What LDL level suggests FH?
An untreated LDL above 5 mmol/L in adults, or above 4 mmol/L in children, is suggestive of FH, particularly with a relevant family history. However, FH can occur at lower LDL levels if the patient is already on lipid-lowering therapy. A calculation of untreated LDL — adjusting for current medications — is part of a proper FH assessment.
My father had a heart attack in his 40s. Should I be tested?
Yes. Premature cardiovascular disease in a first-degree relative, particularly in men before age 55 and women before age 65, is one of the most important indicators for FH screening. Even if your own cholesterol looks normal on a standard test, a specialist assessment that includes Lp(a) and FH criteria is worthwhile.
Does FH affect children?
Yes. Children of a parent with FH have a 50% chance of inheriting the condition. Cholesterol testing in children with a family history of FH can be considered from age 5 to 10. Early identification allows for lifestyle guidance in childhood and earlier treatment decisions in adulthood.
Is FH curable?
FH is not curable in the conventional sense, as it is a genetic condition. However, it is highly manageable with appropriate medication. With good LDL control, the cardiovascular risk of FH patients can be reduced substantially. The condition requires lifelong management and monitoring.
My sibling was diagnosed with FH. Do I need to be tested?
Yes. First-degree relatives of a confirmed FH patient each have a 50% chance of carrying the same mutation. This is called cascade screening, and it is one of the most important strategies for identifying at-risk individuals before a cardiovascular event occurs.
![Diagram of lipoprotein(a) [Lp(a)] particle structure showing apolipoprotein(a) attachment — inherited cardiovascular risk factor](https://static.wixstatic.com/media/faf328_f82f5b3e488845c7b50bd002cf2f2cf6~mv2.png/v1/fill/w_770,h_520,al_c,q_90,enc_avif,quality_auto/faf328_f82f5b3e488845c7b50bd002cf2f2cf6~mv2.png)
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