Performance of Cardiovascular Polygenic Risk Scores in Carotid Stenosis Identification

Area of Science:

• Genetics and Cardiovascular Disease
• Atherosclerosis Research
• Precision Medicine

Background:

• Carotid stenosis is a significant risk factor for ischemic stroke, but predicting its progression is challenging.
• Polygenic risk scores (PRSs) for related cardiovascular diseases (CVD) have shown associations with atherosclerosis.
• The utility of PRSs for predicting carotid stenosis is not well-established.

Purpose of the Study:

• To evaluate the association and discriminative performance of PRSs for CAD, PAD, IS, and cIMT with carotid stenosis.
• To determine if PRSs can improve risk prediction for carotid stenosis.

Main Methods:

• Utilized data from the Mass General Brigham Biobank (MGBB) with validated phenotyping for carotid stenosis.
• Employed logistic regression to assess PRS associations, adjusting for age, sex, and ancestry.
• Evaluated incremental discrimination using changes in Harrell's C-statistic.

Main Results:

• PAD, CAD, and IS PRSs were significantly associated with carotid stenosis (p<0.0001), while cIMT PRS was not.
• The PAD PRS showed the greatest improvement in discrimination (ΔC-statistic 0.017).
• Individuals in the top PRS percentiles for PAD and CAD had a 3-fold increased odds of carotid stenosis.

Conclusions:

• PAD and CAD PRSs may help identify individuals at high likelihood for carotid stenosis.
• These PRSs can serve as adjunctive tools for risk stratification, improving upon traditional risk factors.
• Further research into carotid-specific PRSs in diverse populations is warranted for enhanced precision risk assessment.