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Effect of Disclosing a Polygenic Risk Score for Coronary Heart Disease on Adverse Cardiovascular Events
Mohammadreza Naderian1, Marwan E Hamed1, Ali A Vaseem1
1Department of Cardiovascular Medicine (M.N., M.E.H., A.A.V., K.N., A.T., I.J.K.), Mayo Clinic, Rochester, MN.
Insights
Disclosure of an integrated risk score including polygenic risk score reduced major adverse cardiovascular events (MACE) in individuals at intermediate risk for coronary heart disease (CHD). This likely resulted from increased statin use and lower LDL cholesterol levels over 10 years.
Area of Science:
- Cardiology
- Genetics
- Preventive Medicine
Background:
- The Myocardial Infarction Genes clinical trial assessed risk scores for coronary heart disease (CHD).
- Participants at intermediate CHD risk received either a standard Framingham risk score or an integrated risk score (IRSg) incorporating a polygenic risk score.
- Previous 6-month follow-up showed IRSg led to higher statin initiation and lower LDL cholesterol.
Purpose of the Study:
- To investigate the 10-year impact of disclosing an integrated risk score, including a polygenic risk score, on major adverse cardiovascular events (MACE).
- To determine if polygenic risk score disclosure influences cardiovascular event rates and risk factor management.
Main Methods:
- A 10-year follow-up analysis of the Myocardial Infarction Genes trial (NCT01936675).
- Participants were randomized to Framingham risk score or integrated risk score (IRSg) groups.
- Primary outcome: time to first MACE (cardiovascular death, myocardial infarction, revascularization, stroke).
- Statistical analyses: Cox regression and linear mixed-effects models.
Main Results:
- Over a median 9.5-year follow-up, MACE occurred in 2 participants in the IRSg group versus 9 in the Framingham risk score group (HR, 0.20; P=0.042).
- Fewer participants in the IRSg group underwent CHD diagnostic testing (29% vs 47%; HR, 0.51; P=0.004).
- IRSg participants showed higher statin use and greater LDL cholesterol reduction in the initial years.
Conclusions:
- Disclosure of an integrated risk score, including a polygenic risk score, was associated with a significant reduction in MACE over 10 years.
- The observed benefit is likely mediated by increased statin initiation and improved lipid profiles.
- Polygenic risk scores may enhance cardiovascular risk assessment and preventive strategies.
Background:
In the Myocardial Infarction 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 [IRSg], n=104) that additionally included a polygenic risk score. After 6 months, IRSg 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 IRSg (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 IRSg (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 IRSg (hazard ratio, 0.51 [95% CI, 0.32-0.81]; P=0.004). A higher proportion of IRSg 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.
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