lipid.site

Familial Hypercholesterolemia: Signs and Treatment

Familial hypercholesterolemia (FH) is an inherited condition that keeps LDL cholesterol very high from birth, whatever your diet or exercise. It affects about 1 in 250 to 1 in 313 people, and treatment usually means medication started early, often in combination.

What is familial hypercholesterolemia?

FH leaves the body unable to clear LDL cholesterol (LDL-C) from the blood efficiently, so LDL stays very high from birth. A change in the LDL receptor gene most often causes it.

Because genes drive FH, it responds less to lifestyle changes than ordinary high cholesterol does. Someone with FH can eat well, exercise regularly, and still carry an LDL-C two to three times higher than average.

What causes FH, and how is it inherited?

A change in one of three genes causes FH: most often LDLR (the LDL receptor), less often APOB, and rarely PCSK9. An expert panel convened by the Family Heart Foundation recommends that FH genetic testing cover all three.

The CDC reports that about 60 to 80% of people with FH have an identifiable gene change, so a negative test doesn't rule FH out.

FH is autosomal dominant: one changed copy from either parent is enough. Each child of a parent with FH has a 50% chance of inheriting it, and so does each sibling. Inheriting a changed copy from both parents causes homozygous FH, a much rarer and more severe form that needs specialized care from childhood.

How do I know if I have genetic high cholesterol?

No single sign confirms FH, so clinicians look for several together. FH often causes no symptoms until a cardiovascular event. If your LDL-C has been 190 mg/dL or higher more than once, ask your clinician directly whether FH could be the cause.

  • LDL-C of 190 mg/dL or higher in an adult (160 or higher in a child) without an obvious secondary cause
  • A parent, sibling, or child with a heart attack or stroke before age 55 (men) or 65 (women)
  • A close relative already diagnosed with FH or known to have very high cholesterol
  • Physical signs in some people: tendon xanthomas (cholesterol deposits, often in the Achilles tendon or knuckles) or a pale ring around the iris before age 45

How is FH diagnosed?

Clinicians use your LDL level, family history, and physical exam, often scored with the Dutch Lipid Clinic Network criteria, and confirm with genetic testing when available. They also rule out secondary causes first, such as an underactive thyroid or certain medicines.

Start with a lipid panel, ideally with ApoB and Lp(a), since Lp(a) is a separate inherited risk factor. When one person's gene change is known, relatives can be tested for that exact change (cascade screening).

How is familial hypercholesterolemia treated?

FH usually needs more LDL lowering than one standard statin dose gives. A 50% drop from an LDL-C of 250 mg/dL still leaves 125 mg/dL.

In a Dutch study that followed 2,146 people with FH for about 8.5 years, statin treatment lowered coronary heart disease risk by 76%, and heart attack risk in treated patients was no longer significantly different from the general population.

Treatment often combines medicines early, and starts in childhood or early adulthood because the exposure begins at birth. Ask your clinician which of these fit you and what LDL target to aim for:

  • A high-intensity statin plus ezetimibe as a baseline when LDL starts very high
  • PCSK9 inhibitors, the most effective add-on for reaching target LDL-C
  • Bempedoic acid or inclisiran for some people, especially when statins aren't tolerated

Common questions

▸What is the life expectancy of someone with familial hypercholesterolemia?

Untreated, the CDC reports heart attacks in about 50% of men with FH by age 50 and 30% of women by age 60. In a Dutch study of 2,146 people with FH, those on statins had a heart attack risk no longer significantly different from the general population.

▸What genes cause familial hypercholesterolemia?

Most cases come from the LDL receptor gene (LDLR). Less often the cause is in APOB or PCSK9. An expert panel recommends that FH genetic testing include all three genes.

▸How is familial hypercholesterolemia inherited?

One changed copy from either parent is enough, and each child of a parent with FH has a 50% chance of inheriting it. A changed copy from both parents causes homozygous FH, which is much rarer and more severe.

▸How is familial hypercholesterolemia diagnosed?

Usually from a very high LDL (190 mg/dL or higher in adults), family history of high cholesterol or early heart disease, and physical signs like tendon xanthomas. A genetic test can confirm it, and a negative test doesn't rule FH out.

▸Can familial hypercholesterolemia be treated with diet alone?

No. Diet and lifestyle help, but they rarely bring LDL-C to a safe target on their own because FH is a genetic defect in LDL clearance. Medication is part of effective treatment for nearly everyone with FH.

The full guideRead the complete, referenced version on Preval Health More detail, every study, and the date each figure was checked.

Read next

See it on lipid.site

Sources

Not medical advice. General education from published trials and drug labels, last updated October 2026. lipid.site is not a healthcare provider and cannot tell you what to take or change. Talk to your clinician before starting or stopping any treatment. If you have chest pain or other signs of a heart attack or stroke, call 911.