Hypercholesterolemia

Positive Monogenic Risk

Monogenic risk for Hypercholesterolemia results from a pathogenic variant(s) in any of the following genes: LDLR, APOB, PCSK9, and LDLRAP1. For participants with monogenic risk, recommendations include:

  • Referral to a genetic counselor.
  • Check a lipid profile and Lp(a) level.
  • Consider initiation of lipid-lowering therapy (e.g., statin):
    • Reduce LDL-cholesterol using maximally tolerated statin therapy +/- ezetimibe; PCSK9 inhibitors may be considered if target LDL-C is not achieved despite maximal statin dose.
    • Follow the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol guidance for treating Familial Hypercholesterolemia.
  • Consider referral to a lipid specialist.
  • Emphasize a heart-healthy lifestyle.

High PRS

A high PRS is associated with a 3 to 4 times increased risk for developing Hypercholesterolemia relative to a person not in the high-risk category. The data is based on populations of African, European, Hispanic/Latino and Asian descent. Information is insufficient or not available for populations of other descent. For participants with a high PRS, recommendations include:

  • Check lipid levels.
  • Consider initiation of lipid-lowering therapy (e.g., statin).
  • Consider referral to a lipid specialist.
  • Emphasize a heart-healthy lifestyle.