The World Health Organization’s (WHO) 1998 recommendations to raise global awareness of familial hypercholesterolemia (FH) have fallen short of its goals, specifically in the area of diagnosis. To address gaps and fortify awareness and educational efforts, the global FH community has released new policy recommendations covering a wide range of areas from advocacy to screening, testing and diagnosis, research, and cost.

Clinical labs should take note of the recommendations on lipid screening and genetic testing for FH, Samuel Gidding, MD, corresponding author of the guidelines, told CLN Stat. “One thing lab directors might be able to do is flag lab reports with LDL [low-density lipoprotein] cholesterol levels in the range where a diagnosis of FH might be considered,” he said. In the meantime, the hope is genetic testing for high-risk conditions like FH will become more mainstream, he added.

Labs could also advocate for public policy to eliminate adverse consequences to those identified at risk due to genetic conditions, Gidding suggested.

The nine recommendations appear in JAMA Cardiology. “FH awareness needs to be dramatically raised worldwide—not just in the medical community but among the general population and in the public and governmental agencies responsible for healthcare,” Gidding said. Substantial scientific progress regarding FH has been made since the release of the WHO’s recommendations, he acknowledged. Cascade testing of first-degree relatives of FH-identified adults and first-degree relatives of affected infants are cost-effective programs that have had success in detecting large numbers of previously unidentified individuals. Using scoring systems to identify probands has been another successful tactic in some countries.

Still, many barriers to diagnosing and treating FH exist, including cost, poor knowledge among both physicians and patients about FH and risk for this disease, competing health problems, family influence, and guideline variations. “We now know that coronary heart disease in those with FH can be prevented with early treatment. The bad news is that FH remains under-diagnosed and under-treated with over 90% of cases worldwide not recognized,” Gidding said. Those who do discover their FH usually begin treatment in mid- to late adulthood. But ideally, interventions should start in children at 10 years of age.

To address these concerns and reduce FH burden, the Global Call to Action on FH includes the following recommendations:

  1. Awareness: Efforts should take place to educate the general public and medical community, educational institutions, and healthcare delivery systems about FH and the risks it poses.
  2. Advocacy: Establish country/region-specific advocacy organizations to implement these nine recommendations, as well as a country-specific toolkit that outlines the ins and outs of creating an advocacy organization.
  3. Screening, testing, and diagnosis: Screening should reflect conditions and guidelines of specific countries and be based either on cholesterol levels (with cutoff levels adapted to the country/target population) or positive genetic tests for an LDL-receptor function defect. “A combination of universal child-parent screening and cascade testing of first- and second-degree relatives of index cases is more useful,” the authors suggested.
  4. Treatment: To prevent premature atherosclerotic cardiovascular disease, treatments should be accessible, affordable, and person-centered, beginning in childhood and continuing throughout an individual’s life.
  5. Severe and homozygous FH: Separate guidelines should be created for this condition, defined as either the presence of LDL cholesterol levels ≥400 mg/dL or a pathogenic gene variant in any FH-related genes on 2 different alleles.
  6. Family-based care: Take steps to include the patient’s input and encourage shared decision-making, integrating primary and specialty care, screening of family members, genetic counseling, social support, community health workers, and appropriate resources.
  7. Registries: Provide funds to national and international FH registries for quantifying current practices, identifying gaps between guidelines and healthcare delivery and areas for future resource deployment; disseminate and define best practices; publish outcome metrics for monitoring and standardizing care; and promote FH awareness and screening.
  8. Research: Support studies on the genetic and environmental factors of inherited lipid disorders, development of atherosclerosis, interventions, risk stratification, and pharmacologic factors surrounding new and existing lipid-lowering drugs.
  9. Cost and value: Develop models to calculate value in quality-adjusted life-years or other acceptable metrics that accommodate changes in characteristics over time.

Updates to the FH guidelines took place in a series of stakeholder meetings that included original authors of the WHO document in addition to other FH advocacy leaders, scientific experts, and policymakers, reflecting input from experts in more than 40 countries. “At these meetings, the original [WHO] recommendations were discussed, and consensus was achieved on new recommendations,” Gidding said. This new material circulated to participants for final approval prior to manuscript submission. In May 2019, an international leadership group was established in Geneva to get these recommendations implemented in individual countries and back on the WHO radar, he explained.

The hope is individual countries will adopt the new  recommendations to help prevent atherosclerotic heart disease in individuals carrying FH-associated genes or those with severe hypercholesterolemia. Coronary heart disease is preventable in those with FH by adhering to current evidence-based lipid management guidelines. “However without screening, diagnosis, and appropriate treatment, this prevention goal will not be achieved,” Gidding said.