Familial hypercholesterolemia: signs you might have it and what to do

Familial hypercholesterolemia is the most common serious genetic disorder in medicine. It affects approximately 1 in 250 adults worldwide — about 1.3 million people in the United States alone. Most of them don't know they have it. Here's how to recognize it, how it's confirmed, and what it actually changes about treatment.

What FH is and why it matters

Familial hypercholesterolemia (FH) is a genetic disorder that causes very high LDL cholesterol from birth. The most common form involves mutations in the LDL receptor gene — the gene responsible for clearing LDL from the bloodstream. When these receptors function poorly, LDL accumulates in the blood at two to three times normal levels, even in children eating a healthy diet.

The clinical consequence: untreated FH typically produces LDL in the 190–400 mg/dL range in adults. Because this elevation starts at birth (or conception), the cumulative exposure to elevated LDL is enormous by the time someone reaches middle age. FH is associated with a 20-fold higher lifetime risk of cardiovascular disease compared to the general population, and without treatment, heart attacks often occur in the 30s and 40s in men and 40s and 50s in women.

Despite this, fewer than 10% of people with FH in the United States have been diagnosed. Most will have multiple lipid panels over decades and be told their cholesterol is "a bit high" without ever hearing the words familial hypercholesterolemia.

The signs that should trigger further investigation

LDL above 190 mg/dL in adults

This is the primary trigger. The 2026 AHA dyslipidemia guideline specifically flags LDL ≥190 mg/dL as an indication for statin therapy and as a threshold that warrants evaluation for FH. Not everyone with LDL above 190 has FH — severely unhealthy dietary patterns can also reach this range — but it's high enough that genetic causation should be on the table, particularly when diet appears reasonable.

If you're at the LDL 190 mg/dL level, this context is directly relevant to your next steps.

Family history of early cardiovascular disease

First-degree relatives (parents, siblings) with a heart attack, angina, or coronary artery disease before age 55 in men and age 65 in women. If your father had a heart attack at 48 and your LDL is above 160 mg/dL, FH is a plausible explanation that should be investigated — not explained away as coincidence.

Family history of high LDL or confirmed FH in a first-degree relative is itself a diagnostic criterion. If a parent or sibling has been told their LDL is "extremely high" or has been prescribed high-intensity statin therapy, the question is worth raising about whether FH screening has been done.

Physical signs (present in some, not all)

Tendon xanthomas. These are cholesterol deposits in tendons — most commonly the Achilles tendon (which may feel thickened) and the tendons on the back of the hand. They're firm, yellowish, and painless. Tendon xanthomas are highly specific to FH — they virtually don't occur in non-FH hypercholesterolemia. However, they only appear in a minority of FH patients (roughly 30–40%) and tend to develop over years of elevation, so their absence doesn't rule FH out.

Xanthelasma. Yellowish plaques around the eyelids. These can occur in FH but are less specific — they also appear in other lipid disorders and sometimes in people without significant lipid abnormalities. More of a signal to investigate than a diagnostic finding on its own.

Corneal arcus before age 45. A grey-white arc or complete ring at the outer edge of the cornea. In adults over 60, arcus is common and non-specific. Before age 45, it's a flag worth noting in the context of elevated LDL.

LDL above 160 mg/dL in children

Because FH is present from birth, cholesterol should be screened in children of affected parents. LDL above 160 mg/dL in a child without any obvious secondary cause is a strong indicator of FH and warrants genetic workup. The earlier FH is identified in children, the earlier treatment can prevent decades of cumulative damage.

The diagnostic criteria

The two most widely used clinical scoring systems are the Dutch Lipid Clinic Network (DLCN) score and the Simon Broome criteria. Both combine LDL level, family history, physical exam findings, and (optionally) genetic testing.

The DLCN score assigns points to:

• Family history of premature CVD in a first-degree relative (1–2 points)
• Family history of LDL above the 95th percentile in a first-degree relative (1 point)
• Personal premature CVD history (2 points)
• Tendon xanthomas in patient or first-degree relative (6 points)
• Corneal arcus before 45 (4 points)
• LDL level (1–8 points depending on severity)
• Causative mutation identified (8 points)

Scores above 8 are "definite FH," 6–8 are "probable FH," 3–5 are "possible FH." You don't need a genetic mutation identified to receive a clinical FH diagnosis if the rest of the picture is strong.

Genetic testing: what it finds and doesn't find

FH is caused by mutations in one of three genes — LDLR (LDL receptor, ~80% of cases), APOB (apolipoprotein B, ~5%), or PCSK9 (~1%) — as well as some less common variants. Commercial genetic panels identify a causative mutation in approximately 80% of people with a clear clinical FH diagnosis.

The 20% who don't get a positive genetic result aren't "cleared" — clinical FH can exist without an identified mutation in currently testable genes. Genetic testing is additive to clinical diagnosis, not a replacement for it.

If a causative mutation is found, it dramatically simplifies cascade screening of family members — relatives can be tested with a targeted assay rather than relying on lipid panels alone.

What FH means for treatment

The treatment of FH is the same class of drugs as general high LDL — primarily statins — but the intensity and urgency are categorically different.

Statins work well in FH, despite the impaired LDL receptors. They work by upregulating LDL receptor expression (making more receptors, even if each one functions less efficiently) and reducing LDL production. High-intensity statins (rosuvastatin 20–40 mg, atorvastatin 40–80 mg) typically lower LDL by 50–60% in FH — meaningful even starting from a high baseline.

Most FH patients need more than statins alone. Ezetimibe (blocks intestinal cholesterol absorption) adds another 15–25% reduction. For heterozygous FH patients who remain above LDL targets on maximum tolerated statin plus ezetimibe, PCSK9 inhibitors (evolocumab, alirocumab) provide another 50–60% reduction and are now widely covered for FH by insurance. For homozygous FH — the rare, most severe form — inclisiran and lomitapide are additional options.

Start earlier than you think. The 2026 AHA guideline supports statin therapy in FH starting in childhood (after age 10 in most cases) because the benefit of early treatment in FH is enormous. The cumulative LDL exposure avoided by starting a statin at 12 versus 40 is the difference between a manageable lifetime cardiovascular risk and a very high one.

This is also where ApoB monitoring becomes particularly important in FH treatment. LDL targets in FH are aggressive, and ApoB confirms whether particle count has truly reached goal — not just cholesterol mass. The lipid panel translator shows how ApoB, LDL, and non-HDL interact.

Cascade screening: the family responsibility

FH is autosomal dominant. Every child of an FH-positive parent has a 50% chance of inheriting the condition. Most of those children have never been tested.

If you are diagnosed with FH, cascade screening your first-degree relatives — parents, siblings, children — is strongly recommended by every cardiology guideline. It's the highest-yield single intervention in FH management, and it's often the diagnosis that allows a relative's decade of "borderline high" LDL to finally be understood and treated appropriately.

Many countries have FH registries and organized cascade screening programs. In the US, the FH Foundation (thefhfoundation.org) coordinates screening programs and is a useful resource for navigating the testing and treatment landscape.

Educational resource. Not medical advice. See our methodology and citations.