Coronary Heart Disease

Positive Monogenic Risk

Monogenic risk for Coronary Heart Disease (CHD) results from a pathogenic variant(s) in any of the following genes: LDLR, APOB, PCSK9, and LDLRAP1. A positive monogenic risk increases CHD risk by 2-3-fold. For participants with monogenic risk, recommendations include:

  • Referral to a genetic counselor.
  • Check a lipid profile and Lp(a) level.
  • Consider 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 in patients with Familial Hypercholesterolemia.
  • Consider referral to a lipid specialist.
  • Emphasize a heart-healthy lifestyle.

High PRS

A high PRS (top 5th percentile) is associated with a 1.7-2.3 times increased risk for developing CHD relative to a person not in the high-risk category. The data is based on populations of European, Hispanic/Latino, Asian, and African descent. Information is insufficient or not available for populations of other descent. For participants with a high PRS, recommendations include:

  • Check a lipid profile and Lp(a) level.
  • In those aged ≥40 years, consider further screening such as a coronary calcium scan and treatment with a statin to reduce CHD risk. Shared decision-making is recommended.
  • In those aged <40 years, consider carotid ultrasound to detect plaque/measure intima-media thickness to assess for early disease if such an imaging modality is available.
  • Treat risk factors if present: high blood pressure, diabetes, and high cholesterol.
  • Lifestyle changes: smoking cessation if a smoker, increase physical activity, weight loss if elevated body mass index, and heart-healthy diet.

Positive Family History

Positive family history of CHD is defined as onset of CHD in a male first-degree relative before age 55 years, or in a female first-degree relative before age 65 year. A positive family history of CHD increases CHD risk by 1.5–2 folds. For participants with a positive family history, recommendations include:

  • Check a lipid profile and Lp(a) level.
  • In those aged ≥40, consider further screening such as a coronary calcium scan and treatment with a statin to reduce CHD risk. Shared decision-making is recommended.
  • In those aged <40, consider carotid ultrasound to detect plaque/measure intima-media thickness to assess for early disease if such an imaging modality is available.
  • Treat risk factors if present: high blood pressure, diabetes, and high cholesterol.
  • Lifestyle changes: smoking cessation if a smoker, increase physical activity, weight loss if elevated body mass index, and heart-healthy diet.

10-year CHD Integrated Score

For participants with monogenic risk/high PRS/family history, the GIRA report displays two estimates for the 10-year CHD risk: one calculated using the PCE and the other calculated by combining PRS and PCE. The 10-year CHD risk is calculated for those aged 40-79 years and is applicable only to individuals without known CHD.

More PCE details

For participants with a 10-y CHD risk ≥7.5%, consider shared-decision making regarding initiation of statin therapy to reduce the risk of CHD.