Teymourzadeh, Azin

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 [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.

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.

Introduction: Lp(a) is a causal risk factor for ASCVD that is often elevated in patients with personal or family history (FHx) of ASCVD. The 2019 ESC guidelines recommend universal Lp(a) testing, while the 2019 AHA/ACC guidelines include Lp(a) as a ‘risk enhancer’. We used electronic health records (EHR) to assess utilization of Lp(a) testing in patients with ASCVD, premature ASCVD, and FHx of ASCVD at Mayo Clinic sites in Rochester MN, Phoenix AZ and Jacksonville FL and the Mayo Clinic Health System (MCHS) from 1999-2021. Methods: We ascertained Lp(a) testing using LOINC codes and ASCVD status using validated ICD/CPT-based algorithms. ASCVD included coronary heart disease (CHD), cerebrovascular disease (CVD) (ischemic stroke and/or carotid artery stenosis), peripheral artery disease, and abdominal aortic aneurysm. Premature ASCVD was defined as occurring in males < 55 years and females < 65 years. We ascertained FHx using EHR survey data from 2017-2021. We estimated the proportion of patients with ASCVD, premature ASCVD, or FHx of ASCVD who underwent Lp(a) testing. Results: Between 1999-2021, we identified 310,760 patients with at least 1 ASCVD subtype of whom 66,710 had premature disease. FHx data was available starting 2017. For the timeframe 2017-2021, we identified 267,177 patients with FHx of ASCVD and 90,269 ASCVD patients. As summarized in Table 1, Lp(a) was tested only in a small proportion of patients; 7% of ASCVD patients, 11% of premature ASCVD patients, and 6% of patients with FHx of ASCVD. Premature CHD patients had the highest testing proportion (17%). Conclusions: Our results demonstrate underutilization of Lp(a) testing in patients with personal or FHx of ASCVD. Lp(a) is one of the mediators of “ASCVD residual risk” in patients on statins, and with new Lp(a)-lowering medications in phase III clinical trials, patient and provider education will be needed to increase awareness of Lp(a) as a modulator of ASCVD risk.