- 01High LDL vs a high-LDL gene
Most people with LDL of 190 mg/dL or more do not carry an FH gene (under 2% in Khera 2016), but those who do have far higher heart risk at the same LDL, about 22 times versus about 6 times, because their LDL has been high since birth. A genetic result changes how hard treatment is pushed and whether the family needs testing.
Familial hypercholesterolemia (FH) is an inherited condition in which a faulty gene stops the liver clearing LDL cholesterol, so LDL is high from the day you are born. Artery damage starts in childhood, and untreated FH can cause heart attacks in the 30s, 40s and 50s. High LDL from diet, weight, age and many small genes is common; high LDL from a single gene since birth is rarer and more dangerous at the same number. People with FH who are found and treated early can bring their heart risk close to that of people without it 6, and finding one person usually finds several more in the same family. If your LDL is high but nothing points to an inherited cause, start with our <a href="/conditions/high-cholesterol">high cholesterol</a> page; this one is for when the number is very high or runs in the family.
What goes wrong in familial hypercholesterolemia
LDL, the "bad" cholesterol on your report, travels in the blood in tiny particles. They are cleared by LDL receptors, docking sites on liver cells that grab an LDL particle, pull it inside, and return to the surface to grab another. In FH that loop is broken. Most often the fault is in the receptor gene itself (LDLR); less often it is in the LDL particle (APOB) or in a protein that breaks receptors down too fast (PCSK9).
Whichever gene is involved, fewer receptors work, so LDL stays in the blood longer and the level climbs. Because the problem is clearance, diet alone rarely brings FH cholesterol into a safe range. Food changes help, but by a modest margin, and a person starting at 250 mg/dL is still far above target afterwards.
FH causes early heart disease through cumulative exposure, sometimes counted as LDL-years: the LDL level multiplied by the years it has been there. The European Atherosclerosis Society (EAS) consensus estimated that the burden at which coronary disease tends to appear is reached around age 55 with ordinary LDL, around 35 in untreated heterozygous FH, and in childhood in homozygous FH 2. Starting treatment early slows the climb.
Heterozygous vs homozygous FH
Heterozygous FH (HeFH) means one faulty copy of the gene, inherited from one parent. Homozygous FH (HoFH) means two faulty copies, one from each parent, and it is far rarer and far more severe 11.
| Heterozygous FH (HeFH) | Homozygous FH (HoFH) | |
|---|---|---|
| Gene copies affected | One | Two |
| How common | About 1 in 311 | Roughly 1 in 160,000 to 1 in 300,000 |
| Typical untreated LDL | 190 to 400 mg/dL (4.9 to 10 mmol/L) | Often above 400 mg/dL (10 mmol/L) |
| When heart disease can start | 30s to 50s without treatment | Childhood or teens |
| Visible signs | Often none until adulthood | Skin xanthomas often present in early childhood |
| Who manages it | Primary care doctor or cardiologist, ideally with a lipid clinic | Specialist lipid center from diagnosis |
The blood test numbers that point to FH
A standard lipid panel is where most people first see FH (our guide to <a href="/learn/how-to-read-your-lipid-panel">reading a lipid panel</a> covers every line). The pattern is a very high LDL with triglycerides that are usually normal, which sets FH apart from the mix of <a href="/biomarkers/triglycerides/high">high triglycerides</a> and modestly high LDL that comes with <a href="/conditions/insulin-resistance">insulin resistance</a>. The adult flag used by the 2018 AHA/ACC cholesterol guideline and by the UK Simon Broome criteria is the same number in two units: LDL of 190 mg/dL or 4.9 mmol/L, measured before any treatment 73. Already on a statin? These cutoffs apply to untreated levels, so ask your clinician for your result from before treatment started.
Where an example untreated LDL of 212 mg/dL fallsmg/dL
| Who | Total cholesterol | LDL cholesterol |
|---|---|---|
| Adults | Above 290 mg/dL (7.5 mmol/L) | 190 mg/dL (4.9 mmol/L) or higher |
| Children under 16 | Above 260 mg/dL (6.7 mmol/L) | About 160 mg/dL (4.0 to 4.1 mmol/L) or higher |
CalculatorCholesterol converterYour report in mmol/L and the US cutoffs in mg/dL, or the other way round? Convert both and compare like with like.Work it out Two further markers sharpen the picture. Apolipoprotein B counts LDL-type particles directly, so it can check an LDL that was calculated from a formula; the head-to-head is on our <a href="/compare/apob-vs-ldl">ApoB vs LDL page</a>, and a raised result is read on <a href="/biomarkers/apolipoprotein-b/high">high ApoB</a>. Non-HDL cholesterol, total minus HDL, captures every cholesterol-carrying particle that can enter the artery wall. For how the two main cholesterol numbers differ, see <a href="/compare/hdl-vs-ldl">HDL vs LDL</a>.
Markers to read beside an FH suspicion
Symptoms and signs of FH, and why most people have none
FH usually causes no symptoms at all until heart disease starts. Years of very high LDL can leave cholesterol deposits that a doctor can see or feel, but their absence does not rule FH out: many people with FH, especially those under 30 or already on a statin, have no visible signs.
| Sign | What and where | How strongly it points to FH |
|---|---|---|
| Tendon xanthomas | Firm lumps of cholesterol in the Achilles tendon or the tendons over the knuckles | Strong: worth 6 points on the Dutch score and part of definite FH under Simon Broome |
| Corneal arcus under 45 | A white or gray ring at the edge of the iris | Moderate before 45; common and unremarkable in older adults |
| Xanthelasma | Flat yellow patches on the eyelids | Weak: common in people with normal cholesterol too |
Family history is the strongest clue
FH runs in straight lines through families, so the family history often tells as much as the blood test. The patterns that count are a heart attack, stent or bypass in a parent, sibling or child before 55 in men or 60 in women; a relative already known to have very high cholesterol or FH; and a sudden unexplained death at a young age. A family tree written down before the appointment saves time. For each parent, sibling, grandparent, aunt and uncle, note:
| What to note | Example |
|---|---|
| Any heart event and the age it happened | Father: heart attack at 50 |
| Any known cholesterol number | Sister: LDL around 240 mg/dL |
| Cholesterol medicine started young | Uncle: on a statin from his 20s |
| Early or unexplained deaths | Grandfather: died suddenly at 46 |
How doctors score FH with the Dutch and Simon Broome criteria
Two scoring systems turn the clues above into a probability, and both are clinician tools. The Dutch Lipid Clinic Network (DLCN) score adds points across five groups, counting only the highest-scoring item in each group, and reads the total as definite, probable or possible FH 2. A first-degree relative means a parent, sibling or child.
| Group | Finding | Points |
|---|---|---|
| Family history | First-degree relative with early heart disease, or with LDL higher than 95 in 100 people of their age and sex | 1 |
| Family history | First-degree relative with tendon xanthomas or arcus, or a relative under 18 with LDL higher than 95 in 100 children of their age and sex | 2 |
| Your history | Early coronary heart disease | 2 |
| Your history | Early stroke or narrowed leg arteries (peripheral artery disease) | 1 |
| Examination | Tendon xanthomas | 6 |
| Examination | Corneal arcus before 45 | 4 |
| LDL | 8.5 mmol/L or more (330 mg/dL or more) | 8 |
| LDL | 6.5 to 8.4 mmol/L (250 to 329 mg/dL) | 5 |
| LDL | 5.0 to 6.4 mmol/L (190 to 249 mg/dL) | 3 |
| LDL | 4.0 to 4.9 mmol/L (155 to 189 mg/dL) | 1 |
| DNA | A disease-causing variant in LDLR, APOB or PCSK9 | 8 |
| Result | Over 8: definite. 6 to 8: probable. 3 to 5: possible. Under 3: unlikely. |
The Simon Broome criteria, used across the UK, start from the cholesterol thresholds in the table above. Definite FH also needs tendon xanthomas in the person or a close relative, or a confirmed DNA variant; possible FH needs a family history of early heart attack or of very high cholesterol in a relative 3.
What genetic testing tells you
A genetic test looks for a known disease-causing variant in LDLR, APOB or PCSK9. A positive result confirms FH, earns 8 points on the Dutch score, and gives relatives a precise target to test for. A negative result does not cancel a very high LDL. In a US study of over 26,000 sequenced people, fewer than 2% of those with LDL of 190 mg/dL or more carried an FH variant; the rest had high LDL from many small genetic effects, high Lp(a) or other causes 4.
The same study showed why the gene still matters. At any given LDL level, carriers had far higher coronary risk than non-carriers: compared with people with LDL under 130 mg/dL and no variant, people with LDL of 190 or more had about 6 times the risk without a variant and about 22 times the risk with one 4. Lifelong exposure, starting at birth, is the likely reason. So a positive result changes two things: how hard treatment is pushed, and how urgently the family should be tested.
How Lp(a) can mimic FH
Lipoprotein(a), or Lp(a), is an LDL-like particle whose level is set mostly by genes. Standard lab methods count the cholesterol inside Lp(a) as part of LDL, so a very high Lp(a) can lift a measured LDL into the FH range, and in people who do have FH it adds heart risk of its own. How to read a raised result is on our <a href="/biomarkers/lipoprotein-a/high">high Lp(a) page</a>.
Treatment and how much each medicine lowers LDL
FH treatment is medicine first, with lifestyle as support. A high-intensity statin is the usual starting point, and the 2018 AHA/ACC guideline recommends one for an untreated LDL of 190 mg/dL or higher without running a risk calculator first 7. The 2019 ESC/EAS guidelines aim for at least a 50% fall in LDL and a level below 70 mg/dL (1.8 mmol/L), or below 55 mg/dL (1.4 mmol/L) when there is already artery disease or another major risk factor 8. Most people with FH need more than one medicine to reach these targets; the choice and dose are set by their clinician.
| Medicine class | How it works | Typical LDL lowering |
|---|---|---|
| High-intensity statin (atorvastatin, rosuvastatin) | Slows cholesterol production in the liver, so the liver makes more LDL receptors | About 50% or more 8 |
| Ezetimibe | Blocks cholesterol absorption from the gut | About 20% more on top of a statin 8 |
| PCSK9 antibodies (evolocumab, alirocumab) | Stop PCSK9 destroying LDL receptors | About 60% more on top of a statin in a trial in FH 9 |
| Inclisiran | Silences PCSK9 production; given twice a year after the first doses | About 40% more on top of a statin in a trial in FH 12 |
| Bempedoic acid | Blocks cholesterol production one step earlier than statins | A smaller extra drop |
| HoFH options (evinacumab, lomitapide, LDL apheresis, a dialysis-like filtering of the blood) | Work without needing LDL receptors, or filter LDL out of the blood | Specialist use, mainly homozygous FH 11 |
The medicine with the outcome data in FH
Food, activity and not smoking still matter, because they lower the other risks that stack on top of LDL. Our guide to <a href="/learn/foods-that-lower-cholesterol">foods that lower cholesterol</a> covers the changes with the best evidence. In FH they work alongside medicine, not in place of it, and because LDL-years add up, guidelines generally do not recommend a long diet-only trial; when to start medicine is a decision to make with a clinician.
Children and family screening
Cascade testing means that once one person is diagnosed, their parents, siblings and children are tested, then the wider family as more cases are found. Each first-degree relative has a 50% chance of having FH, so the yield is high. NICE recommends testing the children of an affected parent by age 10 3. The 2018 AHA/ACC guideline says a lipid test once between ages 9 and 11 is reasonable for all children, and earlier, from age 2, when FH runs in the family 7. The 2015 EAS pediatric consensus allows statins to be considered from about age 8 to 10 after diet counseling 10.
What to do if your result looks like FH
- 1Ask for a repeat lipid panelOne high result can be a lab or timing quirk, so your clinician will usually repeat it, often within a few weeks to a few months, ideally at the same lab and not during an illness or a big change in diet. ApoB and a once-in-a-lifetime Lp(a) can be added if they have not been measured.
- 2Ask about other causesA clinician will usually check TSH for the thyroid, kidney and liver tests, and review current medicines, to rule out the look-alikes before the FH label is used.
- 3Write down your family historyHeart events with ages, known cholesterol numbers and cholesterol medicine taken young, for both sides of the family.
- 4Ask about a lipid clinicA lipid specialist can score you, arrange genetic testing and start cascade testing for relatives. An untreated LDL above about 400 mg/dL (10 mmol/L), or yellow lumps on the skin or tendons at a young age, can mean the rarer homozygous form and needs a lipid specialist promptly, not a routine appointment.
- 5Tell your relativesParents, siblings and children each have a 50% chance of carrying the same gene and benefit most from finding out early.
A diagnosis of familial hypercholesterolemia needs a clinician, ideally a lipid specialist, who can repeat your tests, rule out other causes and weigh your family history. Do not stop or change a prescribed medicine on your own. Chest pain or pressure, pain spreading to the arm, jaw or back, sudden breathlessness, fainting, or sudden weakness, facial droop or trouble speaking are emergencies: call 911. A child with yellow bumps on the skin, or anyone with an untreated LDL above about 400 mg/dL, needs a specialist promptly.
Citations
- Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol. 2020;75(20):2553-2566.
- Nordestgaard BG et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-3490.
- National Institute for Health and Care Excellence. Familial hypercholesterolaemia: identification and management (CG71), updated 2019.
- Khera AV et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578-2589.
- Luirink IK et al. 20-year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med. 2019;381(16):1547-1556.
- Versmissen J et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;337:a2423.
- Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082-e1143.
- Mach F et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188.
- Raal FJ et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):331-340.
- Wiegman A et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425-2437.
- Cuchel M et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-2157.
- Raal FJ et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med. 2020;382(16):1520-1530.
Educational context only, not medical advice or a diagnosis. Always discuss your results with a clinician.
