Abstract 4140097: Effect of Disclosing a Polygenic Risk Score for Coronary Heart Disease on Adverse Cardiovascular Events: 10-year Follow-up of the MI-GENES Randomized Clinical Trial

Introduction: The MI-GENES randomized clinical trial (NCT01936675) assessed the effect of disclosing a polygenic risk score (PRS) for coronary heart disease (CHD), in addition to a clinical risk based on Framingham risk score (FRS), on LDL-C levels. The trial enrolled participants from Olmsted County, Minnesota, without cardiovascular disease, at intermediate CHD risk (10-y risk: 5-20%), and not on statins. There was a significant LDL-C reduction in the integrated risk score group (IRS g ; received PRS information in addition to the FRS) compared to the FRS group (FRS g ; received their risk based on FRS), due to more frequent statin initiation. Research Question: Does disclosure of an IRS for CHD lead to a lower rate of major adverse cardiovascular events (MACE)? Methods: Participants were followed from randomization beginning in October 2013 until September 2023 to ascertain cardiovascular events, testing for CHD, and risk factor changes, by blinded review of electronic health records. The primary outcome was time from randomization to the first MACE— defined as cardiovascular death, nonfatal MI, coronary revascularization, and nonfatal stroke. Analyses were done using Cox and linear mixed-effects models. Results: We followed all 203 participants, who completed the MI-GENES trial, 100 in FRS g and 103 in IRS g (mean age at the end of follow-up 68.2±5.2 years, 48% male). During a median follow-up of 9.5 years, 9 MACE occurred in FRS g and 2 in IRS g (HR, 0.20; 95% CI, 0.04 to 0.94; P =0.042, Figure 1A). In FRS g , 47 (47%) underwent at least one test for CHD, compared to 30 (29%) in IRS g (HR, 0.51; 95% CI, 0.32 to 0.81; P =0.004, Figure 1B). IRS g participants had a longer duration of statin therapy during the first four years post-randomization (Figure 1C) and a greater reduction in LDL-C for up to 3 years post-randomization (Figure 1D). No significant differences between the two groups were observed for hemoglobin A1C, blood pressure, weight, and smoking cessation rate during follow-up. Conclusion: The disclosure of 10-year CHD risk that included a PRS to those at intermediate risk was associated with lower incidence of MACE after a decade, likely due to more frequent and prolonged statin use, leading to lower LDL-C levels.