EDITORIALS
Familial Hypercholesterolemia: The Atlantic Divide
R
ecommendations have existed since the 1990s to
screen for familial hypercholesterolemia and
initiate treatment early in life, but uptake has
been poor worldwide.1,2 Two articles in the current
volume of The Journal call attention to the fundamental
differences in approach to familial hyperc-holesterolemia
care across the Atlantic and barriers to further
progress in familial hypercholesterolemia identification
globally.3,4
In Europe, a variety of approaches, specific to the health
care environments in individual countries, have led to
substantial progress in the identification of familial
hypercholesterolemia in well-organized programs, supported
by government funding and abetted by either registries or
centrally organized specialized centers with resources that
include genetic testing.5,6 Cascade screening, the genetic
testing of first-degree relatives of familial hypercholesterole-
mia index cases, has been pioneered most notably in the
Netherlands (approximately 70% of total cases identified)
but also successfully in Norway (about 37% of cases identi-
fied), Spain, the United Kingdom, and on a smaller scale in
other countries. Slovenia began a universal screening pro-
gram for 5-year-old children that now tests approximately
91% of all children in that country. Today, familial hypercho-
lesterolemia screening is considered a Best Practice by the
European Union (https://webgate.ec.europa.eu/dyna/bp-
portal/practice.cfm?id=390). At least 15 countries have
familial hypercholesterolemia screening programs in place
that include children, with approximately 95% diagnosed
by confirmatory genetic testing. In individual countries,
screening may be based on either cholesterol or genetic
testing as a primary measurement and might occur at birth,
in 1-year-old, or older children. Individual programs may
be primarily based either on universal screening or cascade
testing. Most programs recognize that for identification of
all children carrying an familial hypercholesterolemia
variant, some combination of cascade testing, universal
screening, and opportunistic screening is necessary.
Also in this volume of The Journal, Perretti et al report
the experience of one of the newer European programs,
in France, which takes advantage of an familial
hypercholesterolemia registry to identify relatives of
patients, using cascade testing.3 Genetic testing in children
is not performed as routinely in France as in some other
European countries, allowing the authors to study factors
associated with acceptance of early-life treatment for
familial hypercholesterolemia. They found that the presence
of a genetic diagnosis and parental history of heart disease,
as well as older age and longer follow-up, were associated
with a greater prevalence of lipid-lowering medication
use. These insights are built on key elements of successful
European programs: active registries of patients with
familial hypercholesterolemia, the use of genetic testing
for diagnosis, and interdisciplinary teams that include
internal medicine and pediatric care providers integrated
with genetic counseling and other important resources.
In the US, attempts to identify familial hypercholesterole-
mia were first based on opportunistic screening of children
with a positive family history of elevated cholesterol or
premature heart disease, followed by the 2011
American Academy of Pediatrics recommendation for both
opportunistic screening of those at risk combined with
universal cholesterol screening at age 9-11 years.2,7,8
However, conflicting guidelines for cholesterol screening
exist, such as the United States Preventive Services Task Force
determination of insufficient evidence for cholesterol testing
in younger individuals.9 Although pediatricians’ implemen-
tation of cholesterol testing for the identification of familial
hypercholesterolemia has gained limited acceptance
(probably 15%-20% of children are tested), in family
practice, which does not recommend screening for
conditions not given an A grade by the United States
Preventive Services Task Force, pediatric cholesterol
screening occurs less frequently.10 With regard to genetics,
cascade testing for familial hypercholesterolemia has limited
acceptance; less than 10% of children in the US diagnosed
with familial hypercholesterolemia have molecular
confirmation of the diagnosis.11,12
Most assessments of the limited pediatric screening for
familial hypercholesterolemia point to lack of patient and
provider knowledge about familial hypercholesterolemia,
difficulty in getting blood drawn for cholesterol screening,
cost or fears related to genetic testing, and conflicting guide-
lines as key barriers. Hokanson et al, also in this volume of
The Journal, point out a barrier not discussed as prominently,
lack of interest in cardiologists in providing preventive
cardiology care.4 Lack of training and knowledge also feature
prominently as reasons why specialists may be reluctant to
accept referrals. Without the infrastructure, created by
training and personal interest, to manage referrals for
preventive cardiology care, successful screening programs
based in primary care are doomed to fail.
Although I admire the work by Hokanson et al, one has to
question the focus on pediatric cardiology in their survey.4
Around the world, endocrinologists are the primary pro-
viders of lipid specialty care in children; gastroenterologists
and geneticists also may provide specialty care for familial
hypercholesterolemia. Their questionnaire also addresses
smoking cessation; however, pulmonologists and oncologists
The author is on the Editorial Board of The Journal of Pediatrics. He also serves as a
consultant or Esperion.
0022-3476/$ - see front matter. ª 2022 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jpeds.2022.09.021
1
THE JOURNAL OF PEDIATRICS  www.jpeds.com
might also be considered as specialty providers with an
interest in smoking cessation. Tobacco use is a behavior issue,
so why not psychologists or psychiatrists? Or why not
primary care providers themselves? Statins, the first-choice
lipid lowering medications, are safe, and children with
heterozygous familial hypercholesterolemia are otherwise
healthy. Medications for smoking cessation are closer to
medications used for behavioral conditions than medicines
typically prescribed by cardiologists, pulmonologists, or
oncologists.
The evidence base for treatment of familial hypercholester-
olemia in childhood (and for smoking cessation) is now fairly
secure.5,6 It has been shown recently in a variety of settings
that the development of atherosclerosis is tightly associated
with chronic exposure to elevated low-density lipoprotein
cholesterol as is future atherosclerotic heart disease.13
Lipid-lowering clinical trials conducted in childhood show
treatment is safe and reduces atherosclerosis burden.14,15
Treatment of familial hypercholesterolemia at a young age
is at least cost effective and may be cost-saving.5 Successful
familial hypercholesterolemia screening programs exist.
The European experience suggests that programs that
combine universal screening and cascade testing can be
successful.
Innovation and adaptation of existing models of care,
tested by implementation science, are needed to move from
the current inertia regarding familial hypercholesterolemia
care to making familial hypercholesterolemia care main-
stream for children on both sides of the Atlantic. Lessons
from the studies of Perretti and Hokanson are applicable.3,4
We must accept that identifying familial hypercholesterole-
mia at any age in childhood is valuable. We must accept
that familial hypercholesterolemia care should be
family-based, because it is inherited and family-based factors
influence acceptance of clinical recommendations. We must
accept that many different types of providers, with a special-
ized interest in lipids, are capable of caring for patients with
familial hypercholesterolemia. And, we should accept that
considering familial hypercholesterolemia in isolation may
not be the best strategy, either. There are many conditions
in which genetics and other personalized medicine tools
make early identification during childhood useful to families
interested in prevention, including inherited cancers and
type 1 diabetes. Population-based early identification of
conditions has a successful model in newborn screening;
the list of conditions for which similar strategies might be
useful now includes familial hypercholesterolemia. n
Samuel S. Gidding, MD
Genomic Medicine Institute
Geisinger Health
Danville, Pennsylvania
Reprint requests: Samuel S. Gidding, MD, 100 N Academy Dr, Danville, PA
17822. E-mail: ssgidding@geisinger.edu
Volume 256  May 2023
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