Familial Hypercholesterolemia

rarediseases.org/rare-diseases/familial-hypercholesterolemia/

NORD gratefully acknowledges Joshua W. Knowles, MD, PhD, Attending Physician,

Stanford Center for Inherited Cardiovascular Disease and Chief Medical Advisor, The FH
Foundation, Hannah Wand, MS, LCGC, Genetic Counselor, Stanford Center for Inherited
Cardiovascular Disease, and Hannah Ison, MS, LCGC, Genetic Counselor, Stanford Center
for Inherited Cardiovascular Disease, for assistance in the preparation of this report.

Synonyms of Familial Hypercholesterolemia

autosomal dominant hypercholesterolemia

FH
hyperlipoproteinemia, type IIA
LDLR-related familial hypercholesterolemia, autosomal dominant
APOB-related familial hypercholesterolemia, autosomal dominant
PCSK9-related familial hypercholesterolemia, autosomal dominant

Subdivisions of Familial Hypercholesterolemia

heterozygous familial hypercholesterolemia

homozygous familial hypercholesterolemia

General Discussion

Summary

Familial hypercholesterolemia (FH) is a diagnosis which refers to individuals with very

significantly elevated low-density lipoprotein (LDL) cholesterol (LDL-C) or "bad
cholesterol" and an increased risk of early onset of coronary artery disease if not
sufficiently treated. Most commonly, individuals have heterozygous familial
hypercholesterolemia (HeFH), caused by a single DNA variant (alteration) for FH that
they have inherited from one (affected) parent. In rare cases, an individual can have
homozygous familial hypercholesterolemia (HoFH), caused by having two causal FH
DNA variants, where one variant is inherited from each (affected) parent. Individuals
with HoFH typically have a more severe form of disease. For the purposes of this report,
"FH" will refer to HeFH unless otherwise stated.

FH is one of the most common genetic diseases and affects approximately 1 in 250
individuals. Several standardized criteria have been developed to diagnose FH, including
the Dutch Lipid Clinic Network, Simon Broome, and MEDPED diagnostic criteria. A
diagnosis of FH can be made using any criteria. When evaluating someone for FH, it is

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important to rule out secondary causes of elevated LDL-C. If DNA testing is performed
on an individual meeting clinical criteria for FH, most will be found to have a pathogenic
variant in one of three relevant genes (LDLR, APOB, and PCSK9).

In 20-30% of individuals that meet clinical criteria for FH, standard clinical genetic
testing may be negative in individuals due to reasons such as technical limitations (e.g.
clinical sensitivity of current technology) or causal genes not yet discovered. Therefore, a
negative FH genetic test result does not rule out a diagnosis of FH, but may lower the
suspicion for FH in circumstances where a diagnosis of FH is unclear. There is emerging
data for alternative genetic causes for a clinical FH presentation, including a very high
polygenic burden (see Related Disorders section) that should be considered.

Having FH greatly increases the risk of hardening of the arteries (atherosclerosis), which
can lead to heart attacks, strokes and other vascular conditions. Untreated individuals
with FH have a 20-fold increased risk for coronary artery disease (CAD). Untreated men
have a 50% risk of a nonfatal or fatal heart attack (coronary artery blockage) by age 50
years; untreated women have a 30% risk by age 60 years. If one or more other risk
factors for CAD are present, especially cigarette smoking or diabetes mellitus, the risk of
developing symptomatic CAD is even higher.

FH is treatable and the associated cardiovascular disease is largely preventable with

early and intensive treatment, using statins, additional drugs, and other means. Other
non-statin medications include PCSK9 inhibitors, ezetimibe, and bempedoic acid. These
are effective treatments for individuals with FH who have a persistently elevated LDL-C
despite treatment with maximally tolerated statin therapy.

Early identification and treatment of individuals with FH is key to preventing

cardiovascular disease. Underdiagnosis of FH is a problem in most countries as high
cholesterol can be an invisible and undetected problem until it leads to coronary artery
disease. When an individual with FH is identified, it is important to identify other
affected family members through "cascade screening" or "family screening." Family
members who have not yet exhibited cardiovascular symptoms and who are
appropriately treated are likely to live a normal lifespan. Without proper family
screening, family members will have undetected very high cholesterol and are at risk to
develop early onset CAD. It is common for individuals with FH to have a strong family
history of premature CAD (men < 60 years, women <50 years) and sudden cardiac
death. With improved detection and preventative treatment, the prevalence of
premature CAD in families is declining.

HoFH is very rare (~ 1 in 250,000). LDL-C levels are usually, though not always, > 400
mg/dl. Severe vascular disease including CAD and aortic stenosis are often seen by the
teenage years. Without very aggressive treatment including LDL-C apheresis and HoFH
specific medications, mortality is common before age 30.

Introduction

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In 1973, Joseph Goldstein and Michael Brown identified and characterized a cell
membrane protein they called the LDL receptor and the variation in the low-density
lipoprotein receptor gene (LDLR) that interfered with its function. Normally functioning
receptors lower the blood levels of LDL-C by taking up the lipoproteins that carry LDL-C
in the liver. Pathogenic variants in this gene cause a decrease either in the number or
function of the receptors, resulting in the extreme LDL-C elevations seen in FH.
Goldstein and Brown became the first investigators to identify a variation that caused a
metabolic disorder when only a single abnormal gene was present. In 1985 they won the
Nobel Prize in Medicine for this work. Their pioneering work and the subsequent studies
of LDL-C metabolism in FH patients greatly contributed to our knowledge about the link
between cholesterol and heart disease and led to the development of numerous
therapeutic agents that benefit a very large number of individuals with high cholesterol.
Since that time, other genes causing FH such as the apolipoprotein B-100 gene (APOB)
and the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) have been
identified (see below). Importantly, there is a great deal of evidence showing that early
diagnosis and intensive treatment can prevent illness and death due to FH.

Signs & Symptoms

Heterozygous Familial Hypercholesterolemia

Vascular conditions

People with FH have very high levels of LDL-C from birth. In children, LDL-C levels are
usually > 160 mg/dl, but can be lower, and in adults LDL-C is usually > 190 mg/dL. This
very high LDL-C level is toxic to the body and causes atherosclerosis in the arteries over
time. For individuals with FH, the exposure to elevated LDL-C begins at birth. When
untreated, this can lead to premature CAD, cerebrovascular disease, peripheral vascular
disease and/or other serious conditions.

Most common is CAD due to atherosclerotic plaque build-up in the arteries supplying
the heart (atherosclerosis), which can result in chest pain or discomfort (angina), heart
attack (myocardial infarction) or sudden death. Untreated people with FH have an
approximately 10 to 20-fold increased risk for CAD. It is estimated that 1 in 10
individuals with a heart attack at a young age (<50) have FH, and this may be as high as
6 in 10 if there is a family history of CAD and the LDL-C is > 160 mg/dl at the time of the
heart attack.

Less common are cerebrovascular disease, peripheral vascular disease and aortic
aneurysm. Cerebrovascular disease may occur due to cholesterol build-up in the arteries
supplying the brain, which may cause stroke or transient ischemic attack (TIA).

Peripheral vascular disease is due to cholesterol build-up in the arteries supplying the
legs which may cause pain when walking that is relieved by rest (claudication) and at its
most severe, pain at rest or critical lack of blood flow.

Extravascular clinical features of FH

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Xanthomas are firm nodules caused by cholesterol buildup as a result of the very high
levels of LDL-C. The most common sites are the Achilles tendon and the tendons on top
of the hands (less common). Achilles tendon xanthomas may cause tendonitis, an
inflammation of the tendon that may tear or rupture. Tendon xanthomas are seen in
<15% of individuals with HeFH in the current era and in a much higher percentage of
those with HoFH. Xanthesmas are cholesterol deposits on, above or under the eyelids
can be seen in ~5% of patients with FH. They may also be seen in individuals with
normal cholesterol levels, particularly as they age. Corneal arcus is a white, grey or blue
opaque ring around the edge of the cornea in the eye, can be seen in ~30% of patients
with FH. Since corneal arcus is common in African Americans with normal cholesterol
levels and becomes increasingly common in the general population with age, it is only
useful as a diagnostic tool in younger individuals, particularly in those under age 45. Of
note, children with heterozygous FH are less likely to present with these physical exam
findings. Additionally, the longer an individual is treated with statins, the less likely
these extra-vascular findings will be present. Homozygous Familial
Hypercholesterolemia

Individuals with HoFH exhibit extremely high LDL-C levels, usually above 400 mg/dL.
They usually have xanthomas by early childhood. Planar xanthomas affecting the skin on
the hands, elbows, buttocks and knees in a young child are diagnostic for this condition.
Corneal arcus surrounding the entire inside edge of the cornea is often present. Most
individuals with HoFH experience severe CAD by their mid-20’s if not aggressively
treated. Narrowing of the heart valve leading to the aorta (aortic stenosis) often occurs,
which may make it necessary to replace the aortic valve. Very aggressive therapy is
needed to reduce the likelihood of vascular events. Most affected people will require
filtering of their blood (LDL apheresis) and/or medications specifically approved by the
FDA for HoFH (lomitapide, PCSK9 inhibitors or mipomersen).

Often the other medications that are the mainstay of treatment for HeFH (such as
statins) are relatively ineffective in HoFH. This is because the mechanism of action of
statins normally “triggers” the liver to express additional LDL receptors. In the most
severe cases of HoFH, the LDL receptors are completely inactive which makes this
response futile. Statins can be effective in individuals with HoFH if there is some
residual LDL-R activity, or if they have causal DNA variants in the APOB or PCSK9
genes.

Causes

Genetics of FH

HeFH occurs when a child inherits a nonfunctional copy of one of their FH genes (LDLR,
APOB, PCSK9) from an affected parent and a functional copy from their unaffected
parent. Each egg or sperm they produce has a 50% chance of getting the nonfunctional
copy (passing down FH) and a 50% chance of getting the functional copy, Therefore, the
risk of passing the FH from the affected parent to a child is 50% in each pregnancy. New,
spontaneous variants appear to be very rare.

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Most individuals with HoFH have inherited one mutated gene from each parent, such
that each parent has HeFH. These parents have a 25% risk in each pregnancy to have a
child with HoFH, a 50% chance of having a child with HeFH, and a 25% chance that the
child will inherit a normal gene from each parent. The risk is the same for males and
females.

When one parent has HeFH and the other has HoFH, there is a 50% chance with each
pregnancy to have a child with HeFH and a 50% chance to have a child with HoFH.

When one parent has HoFH and the other has two normal genes, all children will have
HeFH.

When both parents have HoFH, all children will have HoFH.

In FH there is a “dose effect” so that HoFH is more severe than HeFH.

Variation by gene

Of patients with identifiable pathogenic gene variants, a LDLR gene variant is the most
common cause of HeFH, accounting for ~90% of pathogenic variants. Since the original
pathogenic variant discovered by Goldstein and Brown, over 2500 other variants in the
same gene have been identified. An adequate number of functioning LDL receptors are
needed to remove cholesterol from the bloodstream.

A pathogenic variant in the APOB gene is responsible for ~10% of FH cases; this
variation is seen most commonly in those of European Caucasian ancestry. It is also
associated with lower baseline LDL-C levels compared to most cases of FH, closer to 160
mg/dl. Apolipoprotein B-100 is a protein that binds to LDL receptors, which enables
uptake of lipoproteins by the liver and reduces the cholesterol level in the blood.
Pathogenic variants in the APOB gene lead to faulty uptake and increased cholesterol
level.

PCSK9 gene variants are responsible for only a small percentage of FH cases. The normal
PCSK9 gene codes for an enzyme that breaks down the cholesterol receptors after they
have done their job. Unlike most pathogenic variants which cause a loss of function of
the affected gene, PCSK9 pathogenic variants actually increase the gene’s function. This
gain in function in PCSK9 leads to excess degradation of LDL receptors and thus an
increase in the LDL-C levels.

Recent research suggests individuals with FH that have variants in different genes
(LDLR, APOB, PCSK9) or of different types of DNA changes may have different
individual risks. However, there is wide enough variation even among those data sets
and it can be difficult to provide personalized risk information by one’s genotype.

Polygenic inheritance

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FH due to a change in LDLR, APOB or PCSK9 is referred to as a monogenic disease,
where a change in any one of those genes is sufficient to cause disease. In contrast, there
is growing evidence to show that some individuals with a clinical FH presentation
(defined by any of the standard diagnostic criteria signs and symptoms) actually have a
polygenic predisposition to hyperlipidemia as an alternative genetic cause to their
disease. Polygenic disease is due to changes in many genes, often broadly related to
cholesterol metabolism. The contribution of any single genetic change is very small and
it takes the combination of these many, changed genes to get significantly elevated LDL-
C. Polygenic hyperlipidemia can present as severe as FH, but can often also present
milder or more variable than monogenic FH because the number of changes inherited by
any one family member is always different. Polygenic hyperlipidemia is described in
more detail in the “Related Disorders” section.

Affected Populations

Recent studies have shown that FH is as common as 1 in 250, making it one of the most
common genetic diseases. However, most individuals go undiagnosed and most are
undertreated given their very high risk. Small subpopulations around the world have a
higher incidence, such as Lebanese Christians (1/85), Afrikaners in South Africa (1/72 –
1/100), French Canadians (1/270), and Ashkenazi Jews originating from Lithuania
(1/67) known as a founder effect.

The frequency of HoFH across populations is estimated to be 1 in 1/160,000 to 1

250,000. HoFH is more likely to occur in countries where the prevalence of HeFH is
very high, especially those where consanguinity (marriage between relatives) is common.

Related Disorders

A diagnosis of FH can be made using any of the accepted standardized diagnostic criteria
described in the “Diagnosis” section. In instances when a diagnosis of FH is suspected
but cannot be definitively confirmed with the available information, genetic testing can
often aid in the assessment. In 2019, an international expert panel published a
consensus paper supporting the utility of FH genetic testing and a statement that genetic
testing should be offered as standard of care.

In instances where genetic testing is negative, the technical limitations and sensitivity of
FH genetic testing cannot rule out FH with certainty but may support the consideration
of alternative explanations for the presenting symptoms. There are several conditions
with overlapping laboratory findings or family history features similar to FH.These
include the following:

1.) Hypercholesterolemia secondary to obesity, diabetes mellitus, hypothyroidism, drugs

such as steroids, or kidney disease. Inheritance follows a non-Mendelian pattern.

2.) Polygenic hypercholesterolemia due to a combination of many small effect genetic

variants in many cholesterol metabolizing genes. Polygenic hypercholesterolemia can be
exacerbated by risk factors such as diabetes mellitus and obesity. Oftentimes, an
individual will have a family history of hyperlipidemia and coronary artery disease

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though the onset of CAD may be later in life. Inheritance follows a non-Mendelian
pattern and family members often present with variable expression of LDL-C levels or
the associated cardiovascular risks.

3.) Autosomal recessive hypercholesterolemia caused by biallelic pathogenic variants in

LDLRAP1. Persons with biallelic pathogenic variants have LDL-C >400 mg/dL (>10
mmol/L) a phenotype resembling HoFH, whereas heterozygotes have normal LDL-C
levels.

4.) Familial combined hyperlipidemia (FCHL) which leads to elevated LDL-C and
triglycerides. While FCHL is a complex polygenic disorder, heterozygous pathogenic
variants in APOB (different than the ones causing FH) and USF1 (associated with
autosomal dominant inheritance) are causative in a minority of families.

5.) Lipoprotein a (Lp(a)) is a cholesterol-like particle which, when elevated (>30 mg/dL),
increases the risk of premature CAD. Lp(a) levels are primarily genetically determined,
and are inherited in an autosomal codominant pattern. Individuals with significantly
elevated Lp(a) levels may display a family history which mimics that of an individual
with FH even if LDL-C levels are normal. Individuals with both FH and elevated Lp(a)
are at a particularly increased risk of premature coronary artery disease.

Diagnosis

FH should be considered in an untreated child with LDL-C above 160 mg/dL, or with
LDL-C above 130 mg/dL and a positive family history of FH or premature heart disease.
In untreated adults, an LDL-C above 190 mg/dL, a personal and/or family history of
early CAD, physical signs such as those described under “Symptoms, or a relative known
to have FH, should increase the suspicion of FH

FH can be diagnosed using DNA testing or by utilizing one of three well-accepted sets of
criteria — Simon Broome (UK), Dutch Lipid Clinic Network (Netherlands), or MEDPED
(US). Of note, the Dutch Lipid Clinic Network criteria are unable to be used in the
pediatric setting. In individuals suspected to have “definite” FH based on clinical criteria,
an FH variant is identified approximately 60-80% of the time. In individuals with
“possible” FH based on clinical criteria, an FH variant is identified approximately 20-
40% of the time. DNA testing confirms the diagnosis and is considered the “gold
standard”, but is not always necessary or feasible. DNA testing should definitely be
considered when it’s not clear whether an individual is affected or not, and is very
helpful for testing family members. Recent studies also suggest that individual risks for
CAD vary among the affected gene and type of DNA variation (substitution vs. partial
deletion of a gene, etc.). Individuals with an LDL-C >190 mg/dL and a FH pathogenic
variant have been noted to have a 10 fold increased relative risk for CAD (compared to
the general population) while those with an LDL-C >190 mg/dL and no FH pathogenic
mutation have a 3-fold increased relative risk for CAD (compared to the general
population). Therefore, individuals who test positive on genetic testing may infer an
increased risk of CAD over an individual with negative genetic testing at any given LDL-
C level.

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Once an individual is diagnosed with FH (either with or without the use of DNA testing)
a process called “cascade screening”, “cascade testing” or “family screening” (testing of
close relatives, in a step-wise fashion) is recommended to identify those with FH before
symptoms appear, so that early and intensive treatment can be initiated and disease and
death prevented. If a pathogenic variant is identified, risk in the patient’s first degree
relatives (parent, sibling, child) and when appropriate, more distant relatives, can be
accessed via DNA testing by tracing the altered gene through the family. If DNA testing
is not performed, another version of cascade screening can be implemented using
cholesterol testing. Cascade screening by either means has been shown to be effective in
finding patients with FH who were not being appropriately treated. A genetic counselor
can help a family through this process. (http://www.nsgc.org/page/find-a-gc-search )

Cascade screening has been shown in numerous studies to be cost-effective and has been
recommended by the National Institute for Health and Clinical Excellence (NICE) in the
UK. The Office of Public Health Genomics at the Centers for Disease Control and
Prevention considers cascade screening of relatives of those with FH a “Tier 1
application” which means that there is good evidence that implementation will prevent
disease and save lives.

HoFH is easily identified in infants and young children by the presence of planar
xanthomas, corneal arcus, and exceedingly high total and LDL-C; LDL-C is usually
greater than 400 mg/dL. The parents are “obligate heterozygotes” who are considered to
have HeFH until proven otherwise.

Clinical Testing and Workup

Evaluations following initial diagnosis

To establish the extent of disease and needs of an individual diagnosed with FH, the
following evaluations are recommended in adults and children:
• Pre-treatment lipid values
• Lipoprotein(a) levels when possible as lipoprotein(a) is an additional risk factor for
CAD
• Exclusion of concurrent illnesses (kidney disease,uncontrolled hypothyroidism, acute
myocardial infarction, infection) that can affect lipid values
• Lipid panel including total cholesterol (TC), low density lipoprotein cholesterol (LDL-
C), high density lipoprotein cholesterol (HDL-C), and triglycerides
• Consultation with a lipid specialist or clinician with expertise in FH
• Medical genetics or a genetic counseling consultation

In children, noninvasive imaging modalities (e.g., measurement of carotid intima-media

thickness) are recommended in some guidelines to help inform treatment decisions.

Standard Therapies

Treatment
Treatment of FH is focused on reducing the LDL-C levels in order to decrease the risk for
atherosclerotic heart disease.

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Adults with FH

Lifestyle intervention

Dietary changes such as restricting saturated fat and eliminating trans-fats have
significant cholesterol-lowering impact. Decreasing dietary cholesterol and increasing
soluble fiber are also helpful. The diet should primarily be made up of vegetables, whole
fruit and grains, nuts and legumes. Seafood, lean poultry and low fat dairy products are
the preferred sources of animal protein. Weight loss and aerobic exercise have modest
effects on cholesterol level but can help to lower blood pressure and blood sugar levels
and thus cardiovascular disease risk.

Cholesterol lowering medication

For adults, treatment should begin as soon as possible after diagnosis. Almost all will
require cholesterol-lowering drug therapy. A firm diagnosis of FH should prompt more
aggressive treatment than would otherwise be undertaken in a patient with “garden
variety” high cholesterol. Some guidelines state that the untreated cholesterol level
should be reduced by at least 50%; others suggest that less than 100 mg/dL is the goal
for individuals without a prior CVD event. LDL-C goals are more stringent (typically <70
mg/dl) when additional risk factors such as diabetes or atherosclerosis are present.
Patients with FH should be referred to a lipidologist if these goals cannot be reached in
the primary care setting. Pharmacotherapy should initially be statin-based, followed by
addition of other drugs if the targeted LDL-C level is not achieved with statins and
lifestyle changes. Preference should be given to one of the higher potency statins
(atorvastatin or rosuvastatin) used at the maximal dose. Muscle injury (rhabdomyolysis)
is the major risk of statins but is very rare, seen in approximately 1/10,000 of those
taking these drugs. Damage to the liver does not occur at a higher rate than in people not
taking a statin. However, myalgia (muscle pain) is a relatively common side effect
occurring in 10-15% of patients. Mild myalgia with or without mild creatine kinase
elevations (less than 5 times the upper limit of normal) are not necessarily a reason to
discontinue statins or other cholesterol lowering medications. Other drugs such as
ezetimibe (Zetia), bile acid sequestrants (colesevelam, Welcol), bempedoic acid
(Nexletol) and icosapent ethyl (Vascepa), or PCSK9 inhibitors (evolocumab; Repatha or
alirocumab; Praluent) (approved in 2015 for the treatment of HeFH and HoFH) may be
necessary. In patients who cannot achieve the desired LDL-C level, a procedure called
LDL apheresis (similar to dialysis for kidney disease) may be necessary. Children with
HeFH

Parents should discuss with the pediatrician when to initiate treatment in a child with
FH. Treatment should be considered when LDL-C level is greater than 190 mg/dl, or
greater than 160 md/dl with at least two other risk factors present. The National Lipid
Association guidelines recommend referral to a lipid specialist, management of diet and
physical activity from an early age, and consideration of statin treatment. Atorvastatin
and rosuvastatin, two of the stronger statins, are approved for use in children by the
Federal Drug Administration, as are all of the weaker statins. The goal is at least a 50%
reduction in LDL-C or LDL-C below 130 mg/dL. Statins can be initiated as early as 8 to

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10 years old; adverse effects of statins in childhood have not been reported. Studies have
shown that children who begin statins have a statistically significant decreased risk of
developing coronary artery disease compared to their parents affected with FH. The goal
of initiating statins in childhood is to reduce the cumulative lifetime burden of exposure
to LDL-C levels.

Children or Adults with HoFH

Early initiation of therapy and monitoring using CT coronary angiography and other
imaging are recommended; these patients often require additional treatment strategies,
as pharmacological treatment and lifestyle changes may not be sufficient. Statins are
usually started as soon as the diagnosis is made (though may not be effective as
explained above). Lomitapide is now a FDA-approved treatment for adults with HoFH,
and should be considered for these patients, especially if LDL-C level cannot be
controlled using other drugs. A PCSK9 inhibitor (evolocumab) was also approved for
HoFH. Additional options include LDL apheresis or liver transplantation.

LDL apheresis

Using a process similar to kidney dialysis, blood is withdrawn from a vein via a catheter
and processed to remove LDL-C particles. Normal blood products are returned via
another catheter. LDL-C levels will decrease approximately 50% but will rise between
apheresis sessions, so they are necessary approximately weekly or every other week. The
procedure is effective and well tolerated though time-consuming and only available in
50-60 sites in the US.

Liver transplantation

Liver transplant is extraordinarily rare and may become even less common with the new
medications available. As the donor liver will have normal LDL receptors, the LDL-C
quickly normalizes after the procedure, but the risks of any organ transplant are
significant and include complications from major surgery and the effects of lifelong
suppression of the immune system. Donor organs are often not available. Patients with
familial pathogenic APOB or PCSK9 gene variants have normal LDL receptors, so liver
transplantation is not an option for them.
Various imaging modalities such as echocardiograms, CT angiograms and cardiac
catheterization may be recommended to monitor individuals with HoFH.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov.

All studies receiving U.S. government funding, and some supported by private industry,
are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in
Bethesda, MD, contact the NIH Patient Recruitment Office:

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Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-
patient-recruitment/

For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com

For more information about clinical trials conducted in Europe, contact:

https://www.clinicaltrialsregister.eu/

Supporting Organizations

American Heart Association

7272 Greenville Avenue
Dallas, TX 75231
Phone: (214) 784-7212
Toll-free: (800) 242-8721
Email: [email protected]
Website: http://www.heart.org
FH Foundation
959 East Walnut Street
Suite 220
Pasandena, CA 91106
Phone: (626) 583-4674
Email: [email protected]
Website: http://www.thefhfoundation.org
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Phone: (301) 251-4925
Toll-free: (888) 205-2311
Website: http://rarediseases.info.nih.gov/GARD/
International FH Foundation
St. Andrews Court
Wellington St.
Oxfordshire, OX9 3WT
Phone: 01235531203
Email: [email protected]
Website: http://www.fh-foundation.org

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 NIH/National Heart, Lung and Blood Institute
P.O. Box 30105
Bethesda, MD 20892-0105
Phone: (301) 592-8573
Email: [email protected]
Website: http://www.nhlbi.nih.gov/

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INTERNET
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[Updated 2016 Dec 8]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors.
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Association. http://www.learnyourlipids.com/ Accessed May 20, 2020.

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Years Published

1991, 1995, 1996, 1998, 2006, 2011, 2014, 2017, 2020

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