MP McGowan, AL Peterson et al. J Pediatr 2024; 113928. Open Access! Universal Pediatric Cholesterol Screening: The Time Has Come!

Background: More than a decade ago, the AAP has previously “endorsed the National Heart, Lung, and Blood Institute’s pediatric cholesterol guidelines, recommending screening for all children between 9 and 11 years of age and, if normal, again between 17 and 21 years of age.” However, these guidelines conflict with “the US Preventive Services Task Force (USPSTF) [which] values the rigorous evidence from randomized controlled trials (RCTs).” The USPSTF has stated “there is insufficient evidence to assess the balance of benefits and harms of universal screening for cholesterol disorders in children and adolescents ages ≤20 years.⁷” In addition, ” recent data suggest only between 2% and 22% of children in the US are screened between the ages of 9 and 11.^{2, 3, 4, 5}”

What is Familial Hypercholesterolemia (FH)?

• Heterozygous FH (HeFH) “should be suspected in a child with an LDL-C of ≥160 mg/dL, after the exclusion of secondary causes and adherence to a heart-healthy diet, especially in the setting of a family history of ASCVD or with a parent with elevated LDL-C”
• “Homozygous FH (HoFH) [is] much rarer, occurring in 1:250 000-1:360 000 people…HoFH should be suspected in children with an LDL-C of ≥400 mg/dL in the setting of a family history of early ASCVD and/or with 1 or both parents having an untreated LDL-C of ≥190 mg/dL¹³“

Why Screening in Childhood is Important?

• “HeFH is the second most common potentially fatal genetic disorder in humans, affecting 1 in 250-300 people.⁸…Homozygous FH (HoFH) [is] much rarer, occurring in 1:250 000-1:360 000 people.”
• Given the limitations of family history and lack of findings on physical exam, universal screening is needed to avert symptomatic atherosclerotic vascular disease (ASCVD).
• Proof that screening can make a difference: “In a 20-year follow-up study, Luirink et al followed a cohort of individuals with genetically confirmed HeFH who had initiated statin therapy in childhood. When compared with their HeFH parents who had not had the benefit of childhood therapy, statins virtually eliminated excess ASCVD risk in adulthood.¹⁶ At age 40, 26% of parents had experienced a cardiac event and 7% had died of ASCVD, whereas only 1% of the those treated as children had needed a vascular procedure (coronary artery stenting) and none had died.¹⁶“
• “Currently available therapies have the potential to completely normalize LDL-C in children with both HeFH and HoFH.^12,17 Such normalization of LDL-C in childhood will presumably prevent future cardiac morbidity and mortality.”
• “An RCT in 214 children with HeFH aged 8-18 years found that those randomized to statin therapy experienced regression of carotid atherosclerosis, whereas those randomized to placebo experienced progression.²⁵ Importantly, no safety concerns with statin treatment were identified.²⁵ …in a follow-up study²⁶ …found that age of statin initiation was an independent predictor of the degree of carotid atherosclerosis, indicating that earlier initiation is protective.²⁶“
• Cost burden of screening could be less in childhood. There is a higher rate of insurance coverage in U.S. for children 0-17 years compared to adults 18-64 years: in 2022, it was >95% compared to 88% respectively.
• Identification of children with HeFH and HoFH has the potential to identify siblings and parents “through a process known as reverse cascade screening.”

Cholesterol-Lowering Therapy:

• Many with HeFH and HoFH will respond to statin therapy
• Some need the addition of ezetimibe
• For severe cases (esp HoFH) injectable agents (eg.  evinacumab-dgnb, an angiopoietin-like3 inhibitor) may be needed

My take: There is a strong case for universal screening for hypercholesterolemia in childhood to prevent cardiovascular disease.

Related blog posts:

• Treatment Outcomes in Children and Adolescents with Hypercholesterolemia
• Conflicting Cholesterol Guidelines –Massive Undertreatment or Massive Overtreatment?
• NEJM: Competing Visions for U.S. Health Policy, Evolocumab for Pediatric Familial Hypercholesterolemia, and the Cervical Cancer Vaccine
• Cholesterol controversy