Polygenic risk score of CAD may help predict preventive strategies such as statin initiation: JAMA

A new study published in the Journal of American Medical Association found that younger people have higher coronary artery disease (CAD) polygenic risk score (PRS) predictive capacity, which can be utilized to more accurately identify individuals with marginal and intermediate clinical risk who should begin statin medication.

Polygenic risk scores for coronary artery disease have not yet been proven to be clinically useful. Therefore, after taking into consideration age and clinical risk, Nicholas Marston and colleagues undertook this investigation to examine if a CAD PRS may perhaps lead to the start of statins in primary prevention.

The UK Biobank, a long-term population study of UK nationals, provided the data for this longitudinal cohort research, which had enrolment beginning on January 1, 2006 and concluding on December 31, 2010, with data updated to mid-2021. In Biobank Japan, a replication study was carried out. All individuals without a history of CAD and not receiving lipid-lowering medication were included in the study. Between January 1 and June 30, 2022, data were examined. A CAD PRS with 241 genome-wide significant single-nucleotide variants was used to categorize polygenic risk for CAD as low, moderate, and high (top 20%). (SNVs). The 10-year atherosclerotic cardiovascular disease (ASCVD) risk assessment and classification of people as low (5%), borderline (5-7.5%), intermediate (7.5-20%), or high risk (≥20%) employed the pooled cohort equations.

The key findings of this study were:

1. From the UK Biobank, 330 201 patients in total were included.

2. During the ten-year follow-up, 4454 people experienced a MI.

3. In spite of having a greater risk prediction at younger ages, the CAD PRS was substantially linked to the risk of MI across all age groups.

4. Patients under the age of 50 who had high PRS had a three- to four-fold higher associated risk of MI than those with low PRS.

5. In Biobank Japan, a similar substantial interaction between CAD PRS and age was seen.

6. When CAD PRS testing was combined with the clinical ASCVD risk score in people under the age of 50, 591 of 4373 borderline risk patients (20%) were risk categorized as intermediate risk, necessitating the start of statin therapy, and 3198 of 7477 borderline or intermediate risk patients (20%) were categorized as low risk, necessitating the end of therapy.

Reference:

Marston, N. A., Pirruccello, J. P., Melloni, G. E. M., Koyama, S., Kamanu, F. K., Weng, L.-C., Roselli, C., Kamatani, Y., Komuro, I., Aragam, K. G., Butterworth, A. S., Ito, K., Lubitz, S. A., & Ruff, C. T. (2022). Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention. In JAMA Cardiology. American Medical Association (AMA). https://doi.org/10.1001/jamacardio.2022.4466