By Annette Boyle
BOSTON—Familial hypercholesterolemia (FH), an 
inherited disorder caused by defects in the genes 
responsible for clearing LDL from the bloodstream, 
accounts for about one in five cases of high choles-
terol levels.1 Now, new therapies, including a twice-
yearly injectable, are expanding choices for a condition 
that affects hundreds of thousands but remains 
largely undiagnosed.
The condition is most commonly associated with 
pathogenic variants in the LDL receptor gene (LDLR), 
but variants in apolipoprotein B (APOB) or proprotein 
convertase subtilisin/kexin type 9 (PCSK9) can also 
cause FH.
With 37% of veterans having hypercholesterolemia, 
FH likely affects nearly 2 million former servicemembers 
who receive care through the VA.2 The condition is most 
commonly associated with pathogenic variants in the LDL 
receptor gene (LDLR), but variants in apolipoprotein B 
(APOB) or proprotein convertase subtilisin/kexin type 9 
(PCSK9) can also cause FH.
Heterozygous FH (HeFH), in which one allele 
carries a pathogenic variant, occurs in approximately 1 
in 250 individuals, ranking it among the most common 
monogenic diseases in the VA and worldwide. Conversely, 
homozygous FH (HoFH), in which both alleles are affected, 
is far rarer — estimated at 1 in 300,000 — but dramatically 
more severe, with LDL-C often exceeding 400 mg/dL and 
cardiovascular disease sometimes appearing before age 20. 
Because of its early presentation and very high cholesterol 
levels, few people with HoFH will qualify for military 
service, making it extremely uncommon in the VA.3
Clinical hallmarks that may prompt suspicion include 
LDL-C of 190 mg/dL or more, xanthomata (cholesterol 
deposits in the tendons of the hands, elbows, or Achilles 
tendons) and corneal arcus. Without treatment, the 
lifelong exposure to severely elevated cholesterol causes 
accelerated atherosclerosis and premature coronary 
artery disease.
Critically, FH is not a condition that responds 
adequately to lifestyle change alone. While diet and 
exercise provide benefit, pharmacotherapy is nearly 
always required. 
More Treatment Options  
Now Available for 
Veterans With Familial 
Hypercholesterolemia
VA research is helping to change 
the massive underdiagnosis 
and undertreatment of familial 
hypercholesterolemia (FH), using the 
unparalleled scale of the Million Veteran 
Program to identify affected veterans and 
return actionable results.  As the treatment 
landscape expands, including multiple 
PCSK9 inhibitor option, clinicians now 
have the tools to bring even severely 
elevated LDL-C under control.
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