Naderian Mohammadreza, Hamed Marwan E, Vaseem Ali A, Norland Kristjan, Dikilitas Ozan, Teymourzadeh Azin, Bailey Kent R, Kullo Iftikhar J
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
medRxiv. 2024 Jul 19:2024.07.19.24310709. doi: 10.1101/2024.07.19.24310709.
The MI-GENES clinical trial (NCT01936675), in which participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (FRS, n=103), or an integrated risk score (IRS, n=104) that additionally included a polygenic risk score (PRS), demonstrated that after 6 months, participants randomized to IRS had higher statin initiation and lower low-density lipoprotein cholesterol (LDL-C).
In a post hoc 10-year follow-up analysis of the MI-GENES trial, we investigated whether disclosure of a PRS for CHD was associated with a reduction in adverse cardiovascular events.
Participants were followed from randomization beginning in October 2013 until September 2023 to ascertain adverse cardiovascular events, testing for CHD, and changes in risk factors, by blinded review of electronic health records. The primary outcome was the time from randomization to the occurrence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and non-fatal stroke. Statistical analyses were conducted using Cox proportional hazards regression and linear mixed-effects models.
We followed all 203 participants who completed the MI-GENES trial, 100 in FRS and 103 in IRS (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 FRS and 2 in IRS (hazard ratio (HR), 0.20; 95% confidence interval (CI), 0.04 to 0.94; =0.042). In FRS, 47 (47%) underwent at least one test for CHD, compared to 30 (29%) in IRS (HR, 0.51; 95% CI, 0.32 to 0.81; =0.004). IRS participants had a longer duration of statin therapy during the first four years post-randomization and a greater reduction in LDL-C for up to 3 years post-randomization. No significant differences between the two groups were observed for hemoglobin A1C, systolic and diastolic blood pressures, weight, and smoking cessation rate during follow-up.
The disclosure of an IRS that included a PRS to individuals at intermediate risk for CHD was associated with a lower incidence of MACE after a decade of follow-up, likely due to a higher rate of initiation and longer duration of statin therapy, leading to lower LDL-C levels.
MI-GENES临床试验（NCT01936675）将冠心病（CHD）中度风险参与者随机分为两组，一组接受弗雷明汉风险评分（FRS，n = 103），另一组接受综合风险评分（IRS，n = 104），后者还包括多基因风险评分（PRS）。结果显示，6个月后，随机分配至IRS组的参与者他汀类药物起始治疗率更高，低密度脂蛋白胆固醇（LDL-C）水平更低。
在MI-GENES试验的事后10年随访分析中，我们调查了CHD的PRS披露是否与不良心血管事件的减少相关。
从2013年10月开始随机分组对参与者进行随访，直至2023年9月，通过对电子健康记录进行盲法审查来确定不良心血管事件、CHD检测情况以及风险因素的变化。主要结局是从随机分组到首次发生主要不良心血管事件（MACE）的时间，MACE定义为心血管死亡、非致命性心肌梗死、冠状动脉血运重建和非致命性中风。使用Cox比例风险回归和线性混合效应模型进行统计分析。
我们对完成MI-GENES试验的所有203名参与者进行了随访，FRS组100名，IRS组103名（随访结束时的平均年龄：68.2±5.2岁，男性占48%）。在中位随访9.5年期间，FRS组发生9例MACE，IRS组发生2例（风险比（HR），0.20；95%置信区间（CI），0.04至0.94；P = 0.042）。在FRS组中，47名（47%）接受了至少一次CHD检测，而IRS组为30名（29%）（HR，0.51；95%CI，0.32至0.81；P = 0.004）。IRS组参与者在随机分组后的前四年他汀类药物治疗持续时间更长，随机分组后长达3年LDL-C降低幅度更大。随访期间，两组在糖化血红蛋白、收缩压和舒张压、体重以及戒烟率方面未观察到显著差异。
对CHD中度风险个体披露包含PRS的IRS与十年随访后MACE发生率较低相关，这可能是由于他汀类药物起始治疗率较高和治疗持续时间较长，导致LDL-C水平较低。
