BACKGROUND AND PURPOSE:

• Heterozygous familial hypercholesterolemia (FH) is a common, heritable disorder that causes premature cardiovascular disease
• Despite the genetic basis of FH, there is no national screening program in the US to identify individuals with pathogenic or likely pathogenic variants
• Bellows et al. (Journal of the American Heart Association) sought to determine if using genetic testing would enhance screening methods based on clinical factors only

METHODS:

• Population
  • UK Biobank participants
• Exposures
  • Clinical characteristics
  • FH variant status
• Study design
  • A regression model to predict the probability of having any FH variants was developed using participant exposure statuses
  • The regression model and modified Dutch Lipid Clinic Network criteria were applied to adult participants in the National Health and Nutrition Examination Survey (NHANES) to estimate the yield of FH screening programs using
    • Dutch Lipid Clinic Network clinical criteria alone (no genetic variant status)
    • Genetic testing alone
    • Combining clinical criteria with genetic testing
• Primary outcomes
  • Accuracy of regression model
  • Yield of potential FH screening programs

RESULTS:

• 49,738 UK Biobank participants used for regression model generation | 39,790 participants in NHANES used to estimate yield of screening
• The regression model accurately predicted FH variant status in UK Biobank participants
  • Observed prevalence: 0.27%
  • Predicted prevalence: 0.26%
  • Area under the receiver-operator characteristic (ROC) curve: 0.88
• In NHANES, estimated yield per 1000 individuals screened
  • With Dutch Lipid Clinic Network clinical criteria alone
    • 3.7 cases (95% CI, 3.0 to 4.6)
  • With genetic testing alone
    • 3.8 cases (95% CI, 2.7 to 5.1)
  • With combination of clinical criteria with genetic testing
    • 6.6 cases (95% CI, 5.3 to 8.0)
• In young adults 20 to 39 years
  • Clinical criteria alone: Estimated to yield 1.3 FH cases per 1000 people screened (95% CI, 0.6 to 2.5)
  • Addition of genetic testing: Estimated to increase to 4.2 FH cases (95% CI, 2.6 to 6.4)

CONCLUSION:

• Combining genetic screening with clinical criteria may improve detection of FH, increasing opportunities for early treatment
• The authors state

Targeted screening strategies, such as offering genetic testing to adults with an LDL‐C ≥160 mg/dL or adults aged 20 to 39 years, may increase screening yield, and could allow for earlier identification and treatment of FH

Learn More – Primary Sources:

Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults

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