Effect of Disclosing a Polygenic Risk Score for Coronary Heart Disease on Adverse Cardiovascular Events

Circ Genom Precis Med. 2025 Mar 28:e004968. doi: 10.1161/CIRCGEN.124.004968. Online ahead of print.

ABSTRACT

BACKGROUND: In the MI-GENES clinical trial (URL: https://www.clinicaltrials.gov; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRS_g], n=104) that additionally included a polygenic risk score. After 6 months, IRS_g participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE).

METHODS: Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models.

RESULTS: We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRS_g (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRS_g (hazard ratio, 0.20 [95% CI, 0.04-0.94]; P=0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRS_g (hazard ratio, 0.51 [95% CI, 0.32-0.81]; P=0.004). A higher proportion of IRS_g participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up.

CONCLUSIONS: Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.

PMID:40151934 | DOI:10.1161/CIRCGEN.124.004968