Familial hypercholesterolemia causes high LDL from birth. Learn how early diagnosis, family screening, and treatment prevent premature cardiovascular disease.

What is Familial Hypercholesterolemia?

High cholesterol is often thought of as a lifestyle problem, but when it affects several members of the same family, a genetic condition may be the underlying cause. Familial hypercholesterolemia (FH) is one of the most common inherited metabolic disorders. It drives LDL cholesterol to dangerously high levels from birth and, if untreated, accelerates the development of atherosclerotic cardiovascular disease.

FH is not rare—affecting approximately 1 in 250 individuals worldwide—yet it remains underdiagnosed. Detecting FH early is crucial: treatment initiated in childhood or early adulthood can reduce the risk of premature heart attack by more than 80%.

FH results from mutations in genes responsible for clearing LDL cholesterol from the bloodstream, most often LDLR, APOB, or PCSK9. These mutations impair LDL receptor activity, causing cholesterol to accumulate in plasma.

• Inheritance: Autosomal dominant; each child of an affected parent has a 50% chance of inheriting FH.
• Typical LDL levels: Adults with FH often exceed 190 mg/dL; children with FH commonly present with levels above 160 mg/dL.
• Physical signs: Tendon xanthomas, early corneal arcus, and strong family history of cardiovascular disease.

Although lifestyle influences lipid metabolism, FH is a genetic condition. Diet alone cannot normalize cholesterol levels.

Why Early Diagnosis and Family Screening Matter

Because FH is inherited, identifying a single case has implications for the entire family. Cascade screening—systematic testing of first-degree relatives—is the most effective way to uncover undiagnosed carriers.

• Children with FH can develop arterial changes before age 10.
• Adults with FH face a 20-fold higher risk of premature myocardial infarction compared with the general population.
• Families identified through cascade testing benefit from timely treatment, breaking the cycle of early cardiovascular disease.

Public health experts, including the Centers for Disease Control and Prevention (CDC), recommend universal lipid screening in children aged 9–11, with selective testing earlier if there is a strong family history【CDC, 2023】.

How should families be screened for Familial Hypercholesterolemia?

When one family member is diagnosed with FH, others are at risk as well. The most effective method of detection is cascade screening, where parents, siblings, and children are tested.

• Children: Should be screened as early as age 2 if there is a strong family history; universal screening is recommended between ages 9 and 11
• Adults: Relatives with LDL cholesterol above 190 mg/dL should be evaluated for FH
• Public health role: Structured programs identify hidden cases and prevent premature deaths from cardiovascular disease

What lifestyle measures are helpful for people with Familial Hypercholesterolemia?

Lifestyle cannot replace medication in FH but it can reduce overall cardiovascular risk. The most effective strategies include:

• Eating a diet rich in vegetables, whole grains, and lean protein
• Reducing saturated and trans fats
• Staying physically active and keeping a healthy body weight
• Avoiding smoking and limiting alcohol

Which medications are considered standard treatment?

For nearly all patients with FH, drug therapy is essential.

• Statins are the first-line therapy and often started in childhood
• Ezetimibe can be added when targets are not reached with statins alone
• PCSK9 inhibitors such as alirocumab or evolocumab can lower LDL even further
• Lipoprotein apheresis may be considered for severe or resistant cases

Are there promising new therapies for FH?

Yes. Several new therapies are in development. RNA-based agents such as inclisiran and mipomersen show promise in lowering LDL cholesterol significantly. Gene therapy is also under investigation as a long-term solution. These options are still being studied but may transform FH management in the near future.

Why should families treat cholesterol as a shared responsibility?

FH is inherited. It does not stop with one individual. Identifying and treating FH protects the entire family. Once one person is diagnosed, parents, siblings, and children should be tested. This collective approach can prevent tragedies and ensure that future generations live longer and healthier lives.

Quick Reference Table

Conclusion

When high cholesterol is present in several family members, it should not be considered a coincidence. Familial hypercholesterolemia is a common genetic condition that can cause heart disease decades earlier than usual.

The solution is clear: early diagnosis, cascade screening, and appropriate treatment. Families who take action can break the cycle of premature cardiovascular disease.

References

1. Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: A scientific statement from the American Heart Association. Circulation. 2015;132(22):2167-2192. doi:10.1161/CIR.0000000000000297
2. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population. European Heart Journal. 2013;34(45):3478-3490. doi:10.1093/eurheartj/eht273
3. Centers for Disease Control and Prevention. Familial Hypercholesterolemia (FH): Awareness and Management. Available at: https://www.cdc.gov/genomics/disease/fh.htm
4. World Health Organization. Cardiovascular diseases (CVDs). Updated 2023. Available at: https://www.who.int/health-topics/cardiovascular-diseases