Familial hypercholesterolemia

Unlike high cholesterol primarily influenced by lifestyle, familial hypercholesterolaemia (FH) is an inherited condition that affects the body's ability to remove LDL (“bad”) cholesterol from the blood. As a result, LDL levels can remain very high from an early age, even with healthy eating and regular exercise.

Normally, the liver uses LDL receptors to remove cholesterol from the bloodstream. In people with FH, genetic changes can reduce the number or function of these receptors, allowing LDL cholesterol to build up in the arteries and increase cardiovascular risk over time.

There are two main forms:

• From one parent (Heterozygous FH): This is the more common form. Your cholesterol levels are typically two to three times higher than they should be, regardless of how healthy you eat or how much you exercise.

• From both parents (Homozygous FH): This is very rare and much more serious. Cholesterol levels are extremely high, and heart issues can develop in very young children.

The risks are significant: without treatment, about half of men with FH will develop heart disease by age 50, and about 30% of women will by age 60, a lower but still substantial risk that emerges somewhat later. The good news is that FH is treatable. Early diagnosis and appropriate treatment can substantially reduce cardiovascular risk and help people with FH live longer, healthier lives.

FH usually causes no noticeable symptoms, allowing high LDL cholesterol to affect the arteries silently for years. When physical signs are present, they can indicate longstanding elevated cholesterol:

• Xanthelasma, yellowish fatty deposits around the eyelids

• Tendon xanthomas, firm fatty deposits over the Achilles tendons or knuckles, highly specific for FH

• Corneal arcus, a white or grey ring around the cornea, particularly significant in people under 45

A family history of premature cardiovascular disease, such as a heart attack or angina at a young age, can also be an important clue that FH may run in the family.

FH occurs when a person inherits a faulty gene that stops the liver from filtering out cholesterol correctly. Since the body can't clear this fat away, it stays in the blood and clogs the arteries.

• The receptor problem (LDLR gene): most people with FH have a mutation in the gene that builds the LDL receptors in the liver. Without these working properly, the liver can't catch and remove cholesterol.

• The binding problem (APOB gene): in some cases, the cholesterol particles themselves are misshapen, making it impossible for them to attach to the liver's receptors and be cleared out.

• The overactive problem (PCSK9 gene): sometimes a specific protein becomes overactive and destroys the liver's LDL receptors before they can do their job.

• Family inheritance: FH is usually passed down through a pattern where only one parent needs to have the gene to pass it on. This means if a parent has FH, there is a 50% chance their child will have it too.

• Polygenic high cholesterol: some people have high cholesterol because of many small genetic variants acting together rather than a single FH-causing mutation. This is different from familial hypercholesterolaemia but can still increase cardiovascular risk and may require treatment.

FH is identified through a combination of blood lipid testing, clinical assessment using validated scoring tools, and genetic testing where available.

Blood tests Elfcare's panel provides the lipid and clinical context markers most relevant to FH assessment:

• LDL cholesterol: the main indicator. Extremely high levels, especially above 5.0 or 8.0, strongly suggest an inherited condition.

• ApoB: measures the total number of particles that cause blockages, which are often much higher in people with FH.

• Lipoprotein(a): a separate genetic risk factor often found in FH patients that doesn't respond to standard lifestyle changes.

• Total cholesterol and non-HDL cholesterol: these provide a complete picture of the total lipid burden currently in the blood.

• HDL and triglycerides: in FH, these are usually normal. This helps doctors tell the difference between a genetic condition and cholesterol issues caused by diet or weight.

• CRP: a marker for inflammation that shows if the high cholesterol is already starting to irritate or damage your blood vessels.

• TSH: used to check your thyroid, as an underactive thyroid can sometimes mimic FH by causing a sudden spike in cholesterol.

The Dutch Lipid Clinic Network (DLCN) score is the gold standard for diagnosing FH. It combines your LDL levels with your family history and physical health markers. A score above 8 confirms a diagnosis of FH. Elfcare provides the foundation for this assessment by delivering the precise blood data and expert consultation needed to calculate your score and guide your next steps.

Why early detection matters

FH exposes the arteries to high levels of LDL cholesterol from an early age, increasing the risk of atherosclerosis and premature cardiovascular disease over time. Early diagnosis and treatment can substantially reduce this risk, particularly when cholesterol-lowering therapy is started before cardiovascular disease develops.

Identifying FH also allows cascade screening of close relatives, helping find other family members who may have the condition. Because FH is inherited, early detection can benefit not only the individual but also their family.

How Elfcare can help

Elfcare's blood panel includes LDL, ApoB, Lp(a), HDL, triglycerides, TSH, and CRP, providing a detailed picture of your cholesterol and cardiovascular risk. Very high LDL cholesterol, particularly when combined with a family history of early cardiovascular disease, can raise suspicion for FH.

ApoB and Lp(a) can provide additional information about cardiovascular risk and may be useful when assessing someone with suspected FH.

If your results show a lipid pattern that may be consistent with FH, we can help guide you toward appropriate follow-up and specialist assessment.