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CHOLESTEROL SERIES · ARTICLE 11 OF 12
Familial hypercholesterolaemia
When high cholesterol runs in the family.
Most high cholesterol is the slow, lifestyle-driven kind we’ve covered in the rest of this series. Familial hypercholesterolaemia (FH) is different. It is a genetic condition that you are born with. It causes very high LDL from childhood. Untreated, it leads to heart attacks two to three decades earlier than in the general population. And — uniquely — it is far more common in South Africa than almost anywhere else in the world.
This article is for anyone whose cholesterol numbers don’t quite fit the standard pattern. If your LDL is unusually high and you’re young, slim, eat reasonably well, exercise, and have a parent or sibling who had a heart attack before 60 — this article is especially for you.
Why South Africa is unusual
FH is roughly 4 times more common in Afrikaner, Indian and Ashkenazi Jewish South African communities than in the global average — about 1 in 100 versus 1 in 250. This is because of “founder effects”: a small number of original settlers carried the gene, and it spread widely through their descendants. Most affected South Africans do not know they have it.
What FH actually is
FH is caused by a fault in one of three genes (most commonly the LDL receptor gene). LDL receptors are the docking ports on liver cells that catch and remove LDL from the blood. When you have FH, half of your receptors don’t work properly. LDL builds up in the blood from birth — usually at levels 2 to 3 times higher than normal.
This is not a lifestyle disease. You can be lean, fit, vegetarian, a non-smoker, and still have an LDL of 6 or 7 mmol/L from your twenties onward. The cholesterol is being made by your liver and not cleared by your liver — independent of what you eat.
Heterozygous vs homozygous FH
Most people with FH inherit one bad copy of the gene from one parent (heterozygous FH — about 1 in 100 South Africans in affected communities). A small number inherit two bad copies — one from each parent (homozygous FH — about 1 in 50 000 to 1 in 100 000). Homozygous FH causes extreme cholesterol levels and heart attacks in childhood; it is rare but well-known to specialist centres.
This article focuses on heterozygous FH, which is far more common and often missed.
How to recognise FH
FH should be suspected when one or more of the following are true:
• LDL above 5.0 mmol/L in an adult, especially under 60.
• LDL above 4.0 mmol/L in someone under 30.
• A parent or sibling with very high cholesterol, OR a heart attack/stroke before age 55 (men) or 60 (women).
• Tendon xanthomas — visible thick lumps over the tendons at the back of the ankle (Achilles tendon) or on the knuckles. These are cholesterol deposits and are highly specific for FH.
• Xanthelasma — yellowish patches around the eyelids. Less specific (also common in older people without FH) but worth noting.
• Corneal arcus — a grey-white ring around the iris of the eye. Common in older people, but in someone under 45 it is highly suggestive of FH.
• Belonging to one of the founder-effect communities — Afrikaner, Indian, Ashkenazi Jewish South African ancestry.
A specific warning sign
If anyone in your immediate family (parent, sibling, child) has had a heart attack or stroke before age 55 — particularly if they were not significantly overweight, smoking heavily, or diabetic — FH should be considered. Get your own cholesterol tested. And, if yours is also high, the rest of the family needs to test too.
The diagnosis
The diagnosis is usually made on a combination of:
• An LDL above 5.0 mmol/L (or above 4.0 in someone under 30).
• A family history of high cholesterol or early heart attack.
• Physical signs (tendon xanthomas, corneal arcus before 45).
The “Dutch Lipid Clinic Network” criteria is the most widely used scoring system, available at public clinics and used in South African lipid clinics. A score above 8 confirms FH; 6 – 8 is probable; 3 – 5 is possible.
Genetic testing can confirm the diagnosis but isn’t always necessary for treatment. It is available in South Africa privately (R3 000 – R8 000) and occasionally through specialist research programmes. The University of Cape Town and University of Stellenbosch both have FH genetics programmes that have, over decades, mapped the most common South African mutations — many of which trace to specific founder families.
Why FH is dangerous if untreated
People with untreated FH have an LDL of 5 – 8 mmol/L for their entire lives. Plaque starts building in the artery walls from childhood. By the time they’re 35 – 50, they often have advanced coronary disease without knowing it.
The numbers are sobering. Without treatment:
• Men with FH have a 50% risk of heart attack by age 50.
• Women with FH have a 30% risk of heart attack by age 60.
• Untreated FH cuts life expectancy by an average of 20 years.
The numbers with treatment are completely different. People with FH who are diagnosed and treated by their 30s, and stay on treatment, have a life expectancy almost identical to the general population.
FH is one of the few conditions where early diagnosis and early treatment fundamentally change the life expectancy.
Family cascade screening — the crucial part
FH is inherited dominantly, which means each child of an affected person has a 50% chance of having it. When one person is diagnosed, the most important next step is screening the rest of the family.
Who to screen
• Every first-degree relative. Parents, siblings, children of the affected person.
• Children from age 2 – 10. Treatment usually starts later, but early diagnosis allows monitoring.
• Second-degree relatives if first-degree is positive. Aunts, uncles, grandparents, nieces, nephews.
What to test
Just a lipid panel — the standard cholesterol blood test. In families with a known mutation, genetic testing is faster and more reliable. But a simple lipid panel catches almost all cases.
The cascade effect
Cascade screening is one of the most cost-effective preventive interventions in medicine. Each person diagnosed leads to an average of 2 – 3 more family members being tested and identified. One conversation around a Sunday lunch table can save several lives over a generation.
If you are diagnosed with FH, the conversation with your parents, siblings, and children is among the most useful medical conversations you will ever have. Suggest a lipid panel. Print this article. Most people who have not been tested are receptive once they understand the stakes.
Treatment — different from regular high cholesterol
FH treatment is more aggressive than treatment for ordinary high cholesterol, for two reasons: the LDL starts very high, and the target needs to be very low because lifelong exposure to high LDL has done more damage.
Lifestyle matters but isn’t enough
The food list from article 5 and the walking plan from article 7 still apply — they lower LDL by 10 – 25%, which is meaningful. But for someone with an FH LDL of 6.5 mmol/L who needs to be under 1.8, even a 25% reduction only gets them to 4.9. Medication is essential.
Statins, usually high-dose
Most FH patients are started on a high-dose statin — rosuvastatin 20 – 40 mg or atorvastatin 40 – 80 mg. The expected LDL drop is 45 – 60%, which often gets them to or near target.
Ezetimibe is added early
When a statin alone isn’t enough — which is common in FH — ezetimibe is added at 10 mg daily. The additional 20% LDL reduction often brings patients to target.
PCSK9 inhibitors for the rest
If a statin plus ezetimibe still doesn’t get LDL low enough, PCSK9 inhibitors (alirocumab or evolocumab) are the next step. They are expensive (R3 000 – R8 000 / month) but South African medical aid formularies cover them for FH in many cases. The State doesn’t currently cover them but there are specialist research access programmes.
Apheresis — for severe cases
In homozygous FH and a few severe heterozygous cases, LDL apheresis (a kind of blood filtration similar to dialysis) is used to physically remove LDL from the blood. This is rare and available only at major centres like Groote Schuur and Tygerberg.
Targets for FH
The LDL target depends on whether you have had a cardiovascular event yet:
Situation LDL target FH with no prior heart event Below 2.6 mmol/L (some guidelines suggest below 1.8) FH with prior heart attack or stroke Below 1.4 mmol/L Homozygous FH As low as achievable
These targets are much tighter than for ordinary high cholesterol, because the lifetime cumulative LDL exposure is what drives the damage, and people with FH start that exposure from birth rather than from middle age.
Living with FH
The good news, repeatedly: FH is highly treatable. People diagnosed and treated early have largely normal life expectancy. The key habits:
• Take your medication every day, for life. Same rule as ordinary cholesterol treatment, but more so.
• Annual lipid panel and follow-up. Adjust dose as needed.
• Annual cardiovascular check-up. ECG, sometimes a stress test or a calcium score CT.
• Heart and Stroke Foundation South Africa has an FH programme — they can put you in touch with patient support networks.
• Family cascade screening for everyone who shares your genes.
• Don’t smoke. Manage BP and blood sugar tightly. All the other risk factors matter even more when you have FH.
• Pregnancy planning for women with FH — statins are stopped during pregnancy. Pre-pregnancy planning with your clinic is important.
The bigger picture
If you are reading this article and have a parent who died of a heart attack before age 55, or who was on cholesterol tablets from a young age — get a lipid panel. If yours is high, get your siblings tested. If theirs is high, get the next generation tested. One conversation in a family can save several lives over a generation.
FH in South Africa is a story about under-diagnosis. Most affected families don’t know they have it until someone has a heart attack in their forties. With cascade screening and modern treatment, that doesn’t have to happen any more.
The final article in the series steps back from any single piece of cholesterol management and takes the long view — the four anchors of sustainable cholesterol care, the first year/fifth year/tenth year arc, and a reading list back to all 12 articles.
Where to get more help
Heart and Stroke Foundation South Africa — heartfoundation.co.za · 021 422 1586 — has an FH programme and family support.
FH South Africa — fhsouthafrica.co.za — patient organisation specifically for FH.
University of Cape Town and Stellenbosch lipid clinics — specialist FH care, including genetic testing programmes.
Your public clinic chronic-care team — initial workup, statin prescription, and referral if needed.
Phila Today Cholesterol Series — next: living well with high cholesterol — the long view.
Phila Today · Article 11 of 12 in the Cholesterol Series