Hypercholesterolemia

Polygenic risk

People with high polygenic risk scores are 3 to 4 times more likely to get hypercholesterolemia than are people who aren't in the high-risk category.

This estimate is based on data about people of African, Asian, European, and Hispanic or Latino ancestry. Information is lacking or not available for those of other ancestries.

For participants with a high polygenic risk score, recommendations include:

  • Check the participant's lipid profile and Lp(a) level.
  • Consider starting lipid-lowering therapy, such as a statin. Therapy recommendations include:
    • Reduce low-density lipoprotein, also known as LDL or as bad cholesterol, using the highest tolerated statin therapy with or without ezetimibe (Vytorin, Zetia and others).
    • Consider using PCSK9 inhibitors if the participant doesn't reach target LDL cholesterol despite receiving the highest statin dose.
  • Follow the 2018 guideline on the management of blood cholesterol in patients with familial hypercholesterolemia from the American College of Cardiology and American Heart Association. 
  • Consider referral to a lipid specialist.
  • Provide guidance for leading a heart-healthy lifestyle, including:
    • Get more physical activity.
    • Eat a heart-healthy diet.
    • Keep body mass index under 25.
    • Limit alcohol intake.
    • Stop smoking if the participant smokes.

Monogenic risk

Risk of hypercholesterolemia can be due to variants in one of these genes:

  • APOB.
  • LDLR.
  • LDLRAP1.
  • PCSK9.

For participants with monogenic risk, recommendations include:

  • Referral to a genetic counselor.
  • Check the participant's lipid profile and Lp(a) level.
  • Consider starting lipid-lowering therapy, such as a statin. Therapy recommendations include:
    • Reduce low-density lipoprotein, also known as LDL or as bad cholesterol, using the highest tolerated statin therapy with or without ezetimibe (Vytorin, Zetia and others).
    • Consider using PCSK9 inhibitors if the participant doesn't reach target LDL cholesterol despite receiving the highest statin dose.
  • Follow the 2018 Guideline on the Management of Blood Cholesterol in Patients With Familial Hypercholesterolemia From the American College of Cardiology and American Heart Association.
  • Consider referral to a lipid specialist.
  • Provide guidance for leading a heart-healthy lifestyle, including:
    • Get more physical activity.
    • Eat a heart-healthy diet.
    • Keep body mass index under 25.
    • Limit alcohol intake.