Familial Hypercholesterolemia

Table of Contents

1. Overview
2. How Common It Is
3. The Genes Behind It
4. What High LDL From Birth Does
5. Physical Signs
6. How It Is Diagnosed
7. Screening in Families and Children
8. Treatments as Guidelines and Trials Report Them
9. Pregnancy and FH
10. Lipoprotein(a) and FH
11. What Remains Unknown
12. Key Research Papers
13. Connections
14. Featured Videos

1. Overview

The liver clears LDL particles with LDL receptors on the surface of its cells. In FH a fault in one of the genes behind this system leaves fewer working receptors, or particles that bind to them poorly, so cholesterol builds up in the blood and is deposited in artery walls, tendons and skin (MedlinePlus Genetics). Much of what is known about the receptor came from studies of skin cells from people with FH, a story told on the site’s page on Goldstein and Brown.

The EAS calls FH “a common genetic cause of premature coronary heart disease” and notes that “once diagnosed, heterozygotes can readily be treated with cholesterol-lowering medication.” Its 2015 statement on children says that people diagnosed and treated early in childhood “can have normal life expectancy.” A clinical diagnosis rests on cholesterol levels, family history and physical signs scored against published criteria; a genetic diagnosis rests on finding a disease-causing variant. The two overlap but are not the same.

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2. How Common It Is

• Hu and colleagues (2020) pooled 42 general-population studies of 7,297,363 people: a prevalence of 1 in 311 (95% confidence interval 1 in 250 to 1 in 397), similar in children (1 in 364) and adults (1 in 303), and 1 in 17 among people with atherosclerotic cardiovascular disease.
• Beheshti and colleagues (2020) pooled 44 studies of 10,921,310 people: 0.32%, or 1 in 313; 1 in 31 among people with ischemic heart disease, 1 in 15 with premature ischemic heart disease and 1 in 14 with an LDL of 190 mg/dL or more.

The CDC gives “about 1 in 311 people”; MedlinePlus Genetics gives “1 in 200 to 1 in 250 people in most countries,” with higher rates in some populations, including Afrikaners in South Africa, Lebanese and Tunisians. Testing of 10,095 children aged 1 to 2 found an FH mutation in 1 in 273 (Wald and colleagues, 2016).

Homozygous FH is put at about 1 in 250,000 to 360,000 by the EAS 2023 statement: roughly 30,000 people worldwide, fewer than 5% of them identified, with at least 10-fold higher rates possible in founder populations such as French Canadians, Afrikaners and Christian Lebanese.

Diagnosis comes late. Among 42,167 adults from 56 countries in the EAS FH Studies Collaboration registry, the median age at diagnosis was 44.4 years (Lancet, 2021).

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3. The Genes Behind It

The EAS 2023 statement gives the shares of FH-causing variants:

• LDLR, the LDL-receptor gene (loss of function): 85% to 90%. Some variants reduce the number of receptors made; others disrupt their ability to remove LDL (MedlinePlus Genetics).
• APOB, the protein on the LDL particle that the receptor binds (variants that bind poorly): 5% to 10%.
• PCSK9 (gain of function): 1% to 3%. PCSK9 binds LDL receptors on liver cells “to promote LDLR degradation within the liver,” in the words of the enlicitide label; variants with the opposite effect, which lower LDL for life, are part of the story of the PCSK9-blocking drugs.

LDLRAP1 causes a rare recessive form, autosomal recessive hypercholesterolemia, under 1% of cases (EAS 2023): a person inherits two faulty copies, and carrier parents usually have normal cholesterol (MedlinePlus Genetics).

The LDLR, APOB and PCSK9 forms are autosomal dominant: one altered copy is enough, typically inherited from an affected parent. The EAS 2023 statement calls FH “semi-dominant”: people with two altered copies have “more extreme LDL-C deviation and more severe clinical features from a younger age,” and children of a parent with HoFH “will have obligate HeFH.” When a family’s mutation is known, roughly 50% of the relatives tested will have inherited it (EAS 2013).

In 10% to 40% of people with a clinical diagnosis, depending on referral criteria, no causative mutation is found; the EAS 2013 statement suggests other genes or a polygenic basis.

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4. What High LDL From Birth Does

A 2017 EAS consensus statement found that mutations reducing LDL-receptor function lead to “markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD,” an effect that “appears to increase with increasing duration of exposure” (Ference and colleagues). In FH the exposure starts at birth.

The cumulative burden. The EAS 2013 statement illustrates this with a running total of LDL cholesterol. A 55-year-old without FH typically reaches about 160 mmol, a burden it describes as sufficient for coronary heart disease to develop. A person with HeFH reaches it by age 35 if untreated, by 48 if treated from age 18 and by 53 if treated from age 10; an untreated person with HoFH reaches it at 12.5.

The untreated course. Untreated men and women with HeFH, with total cholesterol of 8–15 mmol/L (310–580 mg/dL), “typically develop CHD before age 55 and 60, respectively”; people with HoFH (12–30 mmol/L, 460–1160 mg/dL) develop it very early in life and, if untreated, die before age 20 (EAS 2013). The FDA’s 2021 description of HoFH says heart disease can start “when they are teenagers or in their 20s” and that “without aggressive treatment, patients may die before age 30.”

• Simon Broome Register (UK; 282 men and 244 women aged 20 to 74, followed during 1980–89): the standardised mortality ratio for coronary heart disease was 386, where 100 is the rate in England and Wales; it was highest at ages 20 to 39 (9686) and fell with age, with no significant difference between men and women.
• Khera and colleagues (2016; 26,025 sequenced people): compared with an LDL under 130 mg/dL and no mutation, an LDL of 190 mg/dL or more brought a 6-fold higher risk of coronary artery disease without an FH mutation (odds ratio 6.0) and a 22-fold increased risk with one (odds ratio 22.3). Of 1,386 participants with an LDL of 190 or more, only 24 (1.7%) carried an FH mutation.
• Copenhagen General Population Study: 33% of people with definite or probable FH had coronary heart disease, only 48% took a statin, and risk was increased 13-fold in those not on one (EAS 2013).
• FHSC registry: coronary disease in 17.4% of adults, a rate “about two times lower in women than in men.”

Changes start in childhood. Carotid wall thickening may be significant by age 7, and coronary calcification is present in about 25% of 11- to 23-year-olds with HeFH (EAS 2015). In HoFH the 2023 statement describes atherosclerosis “typically affecting the aortic root and coronary ostia” and calcific aortic valve disease that “has become very prevalent with increasing longevity” (see aortic stenosis).

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5. Physical Signs

MedlinePlus Genetics describes three signs of cholesterol deposited outside the arteries:

• Tendon xanthomas: growths most often in the Achilles tendons and the tendons of the hands and fingers. NICE calls them “a distinctive feature of FH.”
• Xanthelasmata: yellowish deposits under the skin of the eyelids.
• Corneal arcus: a gray ring at the edge of the cornea.

In the Dutch Lipid Clinic Network score a tendon xanthoma earns 6 points and corneal arcus before age 45 earns 4. Their absence proves little: NICE states that “the absence of clinical signs (for example, tendon xanthomata) in adults and children and young people does not exclude a diagnosis of FH,” and the EAS 2013 statement notes that in children they “are not reliable clinical criteria as they only appear later; however, if present, they are suggestive of homozygous FH.” NICE does not recommend Achilles-tendon ultrasound for diagnosis, while the EAS reports that it “increases the rate of xanthoma detection.”

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6. How It Is Diagnosed

The EAS 2013 statement lists five elements: family history, personal history of premature coronary heart disease, examination for xanthomas and corneal arcus, very high LDL on repeated measurements, and/or a causative mutation, after other causes such as thyroid, liver or kidney disease are excluded. NICE asks for two LDL measurements to confirm a diagnosis. Standard risk calculators “are not appropriate for FH subjects” (EAS 2013).

Dutch Lipid Clinic Network (DLCN) criteria

The commonest method in prevalence studies (Hu 2020). As tabulated by the EAS, only the highest applicable score in each group counts:

• Family history: first-degree relative with premature coronary heart disease (men under 55, women under 60) or LDL above the 95th percentile: 1; first-degree relative with tendon xanthoma and/or corneal arcus, or children under 18 with LDL above the 95th percentile: 2.
• Personal history: premature coronary heart disease: 2; premature cerebral or peripheral vascular disease: 1.
• Examination: tendon xanthoma: 6; corneal arcus before 45: 4.
• LDL: above 8.5 mmol/L (325 mg/dL): 8; 6.5–8.4 mmol/L (251–325 mg/dL): 5; 5.0–6.4 mmol/L (191–250 mg/dL): 3; 4.0–4.9 mmol/L (155–190 mg/dL): 1.
• DNA: causative mutation in LDLR, APOB or PCSK9: 8.

Above 8 points is “definite” FH, 6 to 8 “probable,” 3 to 5 “possible” and 0 to 2 “unlikely.” The EAS 2015 statement notes the DLCN criteria are not valid in children.

Simon Broome criteria (UK)

In NICE guideline CG71 (appendix F), the threshold is total cholesterol above 7.5 mmol/L or LDL above 4.9 mmol/L in adults, and above 6.7 or 4.0 mmol/L in a child or young person. Definite FH adds tendon xanthomas in the person or a first- or second-degree relative, or DNA evidence of an LDL-receptor, apolipoprotein B or PCSK9 mutation. Possible FH adds a family history of heart attack (before 50 in a second-degree relative, before 60 in a first-degree relative) or of raised total cholesterol. NICE refers people for DNA testing if they meet possible or definite Simon Broome criteria or have a DLCN score above 5.

MEDPED criteria (US)

The MEDPED (Make Early Diagnosis to Prevent Early Death) cut-offs depend on age and on whether the person is a close relative of a known case. Williams and colleagues (1993) found that at a total cholesterol of 310 mg/dL, only 4% of people in the general population would have FH but 95% of first-degree relatives of known cases would. In population screening the criteria require total cholesterol above 360 mg/dL at age 40 or older (270 mg/dL in youth); for first-degree relatives of confirmed cases, above 290 mg/dL at 40 or older and above 220 mg/dL in youth.

Children

The EAS 2015 statement uses an LDL of 5 mmol/L (190 mg/dL) or more; 4 mmol/L (160 mg/dL) or more with a family history of premature coronary heart disease and/or high baseline cholesterol in one parent; or 3.5 mmol/L (130 mg/dL) or more when a parent has a known genetic defect.

Genetic testing

A 2018 international expert panel recommended that FH genetic testing “become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives,” covering LDLR, APOB and PCSK9, for a definitive diagnosis, risk information, treatment uptake and cascade testing. The EAS 2015 statement notes that testing first-degree relatives for a known family mutation has, in theory, 100% sensitivity and specificity, against 70% to 85% for a clinical diagnosis.

Homozygous FH

NICE sets the threshold for a clinical diagnosis of HoFH at an LDL above 13 mmol/L in adults and above 11 mmol/L in children and young people. Because LDL below 13 mmol/L had been reported in several cohorts of genetically confirmed HoFH, the EAS 2023 statement lowered its own threshold: an untreated LDL above 10 mmol/L (400 mg/dL) “is suggestive of HoFH and warrants further evaluation,” supported by xanthomas before age 10 and/or FH-range LDL in both parents.

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7. Screening in Families and Children

Cascade screening. The EAS 2013 statement calls testing the relatives of known patients “the most cost-effective approach for identification of new FH subjects,” starting with parents, brothers and sisters and children. NICE recommends DNA-based cascade testing of first-, second- and, when possible, third-degree relatives of anyone with a genetic diagnosis. In the Netherlands more than 28,000 people with FH had been identified, almost 23,000 of them by cascade screening (EAS 2015).

From child to parent. Testing 10,095 children aged 1 to 2 at routine immunization visits identified, for every 1,000 children screened, 8 people with positive FH screening results: 4 children and 4 parents (Wald and colleagues, 2016).

Universal screening of children. The bodies that have weighed it differ:

• The National Heart, Lung, and Blood Institute’s 2011 expert panel recommended universal lipid screening at ages 9 to 11 and once at 17 to 21, with testing at ages 2 to 8 only for a positive family history or other risk conditions.
• The 2026 ACC/AHA guideline, in the AHA’s summary, notes that “children may have high cholesterol due to inherited conditions or lifestyle habits” and that “cholesterol screening is recommended for all children between the ages of 9-11 years not previously screened.”
• The EAS 2015 statement recommends testing children with suspected HeFH from age 5 (earlier if HoFH is suspected) and says universal screening “may also be considered”; in Europe it had been implemented only in Slovenia.
• The US Preventive Services Task Force concluded in 2016 and again in 2023 that “the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger.”

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8. Treatments as Guidelines and Trials Report Them

NICE recommends a high-intensity statin for all adults with FH, aiming for at least a 50% fall in LDL from the untreated level, with ezetimibe on its own as an option for adults who cannot take or tolerate a statin. The 2026 ACC/AHA guideline, in the AHA’s summary, sets LDL goals of under 100 mg/dL (borderline or intermediate risk) and under 70 mg/dL (high risk) for preventing a first heart attack or stroke, and under 55 mg/dL for people with atherosclerotic disease at very high risk; the summary does not say where FH fits. More on the drugs is on the cholesterol management page.

Heterozygous FH

• Statins. Placebo-controlled trials were not run in FH when statins were introduced because “it was considered unethical to withhold causal treatment from patients with an inborn error of lipid metabolism.” A Dutch cohort of 2,146 patients followed for a mean of 8.5 years found a 76% lower risk of coronary heart disease with statins (hazard ratio 0.24), and treated patients’ heart-attack risk was not significantly different from an age-matched general-population sample; the authors note the study was observational (Versmissen and colleagues, 2008).
• From childhood. A 20-year follow-up of 214 children from an earlier pravastatin trial found mean LDL down 32%, from 237.3 to 160.7 mg/dL, and carotid thickening no faster than in unaffected siblings. By age 39, cardiovascular events had occurred in 1% of them against 26% of their affected parents, and cardiovascular deaths in 0% against 7% (Luirink and colleagues, 2019). The EAS 2015 statement places the start of statins at age 8 to 10.
• PCSK9 antibodies (injections every 2 to 4 weeks). In RUTHERFORD-2 (331 patients), evolocumab lowered LDL by 59.2% (every 2 weeks) and 61.3% (monthly) more than placebo at 12 weeks; nasopharyngitis (9% vs 5%) and muscle-related events (5% vs 1%) were the most common adverse events more frequent than with placebo.
• Inclisiran, a small interfering RNA that inhibits the liver’s production of PCSK9. In ORION-9 (482 adults; injections on days 1, 90, 270 and 450), LDL at day 510 was down 39.7% with inclisiran and up 8.2% with placebo, a difference of 47.9 percentage points; adverse events were similar.
• Enlicitide, a daily tablet approved on July 15, 2026. In CORALreef HeFH (303 adults, all on statins, 64.4% also on ezetimibe; average LDL 119 mg/dL), LDL fell 58.2% with the drug and rose 2.6% with placebo at 24 weeks, a difference of 59.4% (Ballantyne and colleagues, 2026). The label lists diarrhea (7% vs 2%) and dizziness (9% vs 4%) as more frequent than with placebo.
• Lipoprotein apheresis, which removes LDL from the blood in repeated sessions, is limited by NICE to exceptional heterozygous cases; the EAS 2013 statement says it “can be offered in homozygotes and in treatment-resistant heterozygotes with CHD.”

RUTHERFORD-2, ORION-9 and CORALreef HeFH each had a change in LDL as the primary end point, not heart attacks or strokes; PCSK9 antibody outcome trials in wider groups are described in the oral PCSK9 report.

Homozygous FH

The EAS 2023 statement explains that in HoFH the response to statins, ezetimibe and PCSK9 inhibitors depends on how much LDL-receptor activity remains, while lomitapide, ANGPTL3-directed therapy and apheresis work regardless. It calls combination drug treatment plus apheresis foundational, with apheresis in children ideally by age 3 and not later than 8, usually every one or two weeks.

• Evinacumab, an ANGPTL3 antibody infused every 4 weeks. In ELIPSE HoFH (65 patients on maximal therapy; average LDL 255.1 mg/dL), LDL fell 47.1% with evinacumab and rose 1.9% with placebo at 24 weeks, a difference of 49.0 percentage points or 132.1 mg/dL, including in patients with virtually absent receptor activity; adverse events were similar. FDA-approved for HoFH on February 11, 2021, it is now labeled for ages 1 and up, with warnings of serious hypersensitivity reactions and possible fetal harm based on animal studies.
• Lomitapide, an oral microsomal triglyceride transfer protein inhibitor that acts on the production of very low-density lipoproteins, the precursor of LDL (EAS 2023). In 29 adults, LDL fell 50% at 26 weeks and was 38% below baseline at 78 weeks; gastrointestinal symptoms were the most common adverse event. Its label carries a boxed warning for liver toxicity (10 of the 29 trial patients, 34%, had at least one liver-enzyme reading at three or more times the upper limit of normal), restricts it to a safety program and contraindicates it in pregnancy.
• Alirocumab was approved by the FDA for adults with HoFH on April 1, 2021; in a 12-week trial LDL fell 27% in 45 patients on the drug and rose 9% in 24 on placebo.
• Liver transplantation is described by the EAS 2023 statement as a possible last resort for a small subset, particularly severely affected young children; case reports show LDL normalizing within a few weeks and staying normal up to 28 years.

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9. Pregnancy and FH

LDL can rise by 25% to 50% in the second and particularly the third trimester, and the absolute rise is much greater in FH, especially HoFH (EAS 2023).

Statins. In July 2021 the FDA asked statin makers to remove the contraindication against use in all pregnant patients. It still advises that most patients stop statins once they learn they are pregnant, but expects the change to enable individual decisions about benefit and risk, “especially for those at very high risk of heart attack or stroke. This includes patients with homozygous familial hypercholesterolemia and those who have previously had a heart attack or stroke.” Observational studies, it reported, “have not identified a drug-associated risk of major birth defects when controlling for other risks such as diabetes” but are insufficient to determine miscarriage risk; it advises against breastfeeding while taking a statin.

Guideline positions. NICE (2008 wording) states that “in general, there is no reason to advise against pregnancy or breastfeeding in women with FH,” and advises women not to take lipid-modifying drugs when planning a pregnancy or during one, because of the potential risk of fetal abnormality, stopping them 3 months before trying to conceive. The 2026 ACC/AHA guideline, in the AHA’s summary, lists among its special considerations “deferring most lipid-lowering therapies during conception, pregnancy and lactation.” For women with HoFH the EAS 2023 statement calls pregnancy “potentially life-threatening,” recommends weekly or fortnightly apheresis during it, and reports that where apheresis is unavailable, continuing a statin, or reintroducing a statin plus other therapy from the second trimester, “appears to be safe.” Bile acid sequestrants such as colesevelam are not linked to more birth defects, it adds, but data are scarce and efficacy limited.

Newer drugs. The enlicitide label says it “may cause fetal harm when administered to pregnant patients based on the mechanism of action”; the evinacumab label calls for contraception during treatment and for at least 5 months after the last dose; lomitapide is contraindicated in pregnancy.

Treatment time lost. A survey of 102 women with FH in Norway and the Netherlands found a median of 2.3 years off statins related to pregnancy, a median 18% of potential treatment time; 86% wanted more information on pregnancy and breastfeeding (Klevmoen and colleagues, 2021).

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10. Lipoprotein(a) and FH

Lipoprotein(a), or Lp(a), is a cholesterol-carrying particle whose level, in the AHA’s words, is “largely genetically determined.” The 2026 ACC/AHA guideline, as the AHA summarizes it, recommends measuring it at least once in adulthood, and the EAS 2023 statement includes it in the initial work-up for HoFH.

It can look like FH, and it adds to the risk. In 46,200 people from the Copenhagen General Population Study, mean Lp(a) rose from 23 mg/dL in people unlikely to have FH to 32 mg/dL with possible and 35 mg/dL with probable or definite clinical FH; after an estimate of the cholesterol carried in Lp(a) was subtracted from each person’s LDL, the trend disappeared (24, 22 and 21 mg/dL). High Lp(a) cholesterol accounted for a quarter of all clinical FH diagnoses, while Lp(a) was similar in people with and without FH mutations. Against people unlikely to have FH with Lp(a) of 50 mg/dL or less, the hazard ratio for heart attack was 3.2 with clinical FH and Lp(a) of 50 mg/dL or less, and 5.3 with clinical FH and Lp(a) above 50 mg/dL. The authors concluded their findings suggest all individuals with FH have Lp(a) measured (Langsted and colleagues, 2016). In CORALreef HeFH, median Lp(a) fell 24.7% with enlicitide and 1.6% with placebo.

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11. What Remains Unknown

• Outcomes with the newer drugs in FH. The FH trials of PCSK9 antibodies, inclisiran and enlicitide measured LDL. Enlicitide’s outcome trial, CORALreef Outcomes, lists an estimated primary completion date of November 2029, and the pediatric HeFH study the FDA requires is due in January 2036.
• Randomized statin data. Statins’ effect on hard end points in FH has not been tested against placebo; the evidence comes from cohorts and from the pediatric follow-up, which compared treated children with their affected parents.
• Universal child screening. The USPSTF found the evidence insufficient in 2016 and 2023, while the NHLBI panel and the 2026 ACC/AHA guideline recommend screening at ages 9 to 11.
• The global count. Only 17 of 195 countries had reported a general-population prevalence (Beheshti 2020).
• Mutation-negative FH. When no mutation is found, MedlinePlus Genetics states, “the cause of the condition is unknown.”
• Pregnancy. Whether off-statin periods raise long-term risk “needs to be further elucidated” (Klevmoen 2021).
• HoFH in children. Data with the newer agents “are, however, limited in children with HoFH” (EAS 2023).

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Key Research Papers

Each paper was checked against PubMed and Crossref, and its abstract read, before it was cited.

1. Hu P, Dharmayat KI, Stevens CAT, et al. (2020). Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis. Circulation 141(22):1742-1759. — PubMed PMID: 32468833
2. Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG (2020). Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. Journal of the American College of Cardiology 75(20):2553-2566. — PubMed PMID: 32439005
3. Nordestgaard BG, Chapman MJ, Humphries SE, et al. (2013). 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. European Heart Journal 34(45):3478-3490a. — PubMed PMID: 23956253
4. Wald DS, Bestwick JP, Morris JK, et al. (2016). Child-Parent Familial Hypercholesterolemia Screening in Primary Care. New England Journal of Medicine 375(17):1628-1637. — PubMed PMID: 27783906
5. Cuchel M, Raal FJ, Hegele RA, et al. (2023). 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance. European Heart Journal 44(25):2277-2291. — PubMed PMID: 37130090
6. EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) (2021). Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). The Lancet 398(10312):1713-1725. — PubMed PMID: 34506743
7. Ference BA, Ginsberg HN, Graham I, et al. (2017). Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal 38(32):2459-2472. — PubMed PMID: 28444290
8. Scientific Steering Committee on behalf of the Simon Broome Register Group (1991). Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ 303(6807):893-896. — PubMed PMID: 1933004
9. Khera AV, Won HH, Peloso GM, et al. (2016). Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia. Journal of the American College of Cardiology 67(22):2578-2589. — PubMed PMID: 27050191
10. Wiegman A, Gidding SS, Watts GF, et al. (2015). Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. European Heart Journal 36(36):2425-2437. — PubMed PMID: 26009596
11. Williams RR, Hunt SC, Schumacher MC, et al. (1993). Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. American Journal of Cardiology 72(2):171-176. — PubMed PMID: 8328379
12. Sturm AC, Knowles JW, Gidding SS, et al. (2018). Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. Journal of the American College of Cardiology 72(6):662-680. — PubMed PMID: 30071997
13. US Preventive Services Task Force; Barry MJ, Nicholson WK, Silverstein M, et al. (2023). Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA 330(3):253-260. — PubMed PMID: 37462699
14. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. (2008). Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 337:a2423. — PubMed PMID: 19001495
15. Luirink IK, Wiegman A, Kusters DM, et al. (2019). 20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia. New England Journal of Medicine 381(16):1547-1556. — PubMed PMID: 31618540
16. Raal FJ, Stein EA, Dufour R, et al. (2015). PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. The Lancet 385(9965):331-340. — PubMed PMID: 25282519
17. Raal FJ, Kallend D, Ray KK, et al. (2020). Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. New England Journal of Medicine 382(16):1520-1530. — PubMed PMID: 32197277
18. Ballantyne CM, Gellis L, Tardif JC, et al. (2026). Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA 335(2):129-139. — PubMed PMID: 41206969
19. Raal FJ, Rosenson RS, Reeskamp LF, et al. (2020). Evinacumab for Homozygous Familial Hypercholesterolemia. New England Journal of Medicine 383(8):711-720. — PubMed PMID: 32813947
20. Cuchel M, Meagher EA, du Toit Theron H, et al. (2013). Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. The Lancet 381(9860):40-46. — PubMed PMID: 23122768
21. Klevmoen M, Bogsrud MP, Retterstøl K, et al. (2021). Loss of statin treatment years during pregnancy and breastfeeding periods in women with familial hypercholesterolemia. Atherosclerosis 335:8-15. — PubMed PMID: 34520888
22. Langsted A, Kamstrup PR, Benn M, et al. (2016). High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. The Lancet Diabetes & Endocrinology 4(7):577-587. — PubMed PMID: 27185354

PubMed Topic Searches

1. PubMed: Familial hypercholesterolemia cascade screening
2. PubMed: Statins in children with familial hypercholesterolemia
3. PubMed: Treatment of homozygous familial hypercholesterolemia
4. PubMed: Familial hypercholesterolemia and pregnancy

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Connections

• Cholesterol Management
• Atherosclerosis
• Coronary Artery Disease
• Heart Attack
• Aortic Stenosis
• Lipid Panel
• Apolipoprotein B (ApoB)
• Lipoprotein(a)
• Coronary Calcium Score
• Genetics
• Goldstein & Brown: The LDL Receptor
• Cholesterol, LDL and the Artery Wall
• FDA Approves the First Cholesterol-Lowering PCSK9 Pill
• Statins After 70: STAREE Trial Results
• New Cholesterol Guideline Lowers LDL Targets

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