Background:Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing.Methods:PRSs were developed using least absolute shrinkage and selection operator regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines.Results:In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90–0.92) and 0.74 (95% CI, 0.73–0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the European Society of Cardiology/European Atherosclerosis Society lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate.Conclusions:A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.

中文翻译：

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遗传预测的 Lp(a)（脂蛋白 [a]）和 ApoB 水平在心血管风险评估中的效用

背景：当前的血脂指南建议测量 Lp(a)（脂蛋白[a]）和 ApoB（载脂蛋白 B）用于动脉粥样硬化性心血管疾病风险评估。Lp(a) 和 ApoB 的多基因风险评分 (PRS) 可以识别出 Lp(a) 或 ApoB 不太可能升高的个体，从而减少此类建议的检测。方法：PRS 是使用最小绝对收缩和选择算子回归在 273 222 和356 958 名英国白人血统的英国生物样本库参与者分别针对 Lp(a) 和 ApoB，并在 60 771 名英国生物样本库和 15 050 名欧洲癌症和营养前瞻性调查参与者中分别进行了验证。然后，我们根据当前的脂质指南评估了基于这些 PRS 不太可能从 Lp(a) 或 ApoB 测量中受益的参与者比例。 结果：在英国生物库和欧洲癌症和营养前瞻性研究-诺福克队列中，PRS 预测的 Lp(a) 和 ApoB 用于识别 Lp(a) 和 ApoB 升高的个体的受试者工作曲线下面积至少为 0.91（ 95% CI, 0.90–0.92) 和 0.74 (95% CI, 0.73–0.75)。Lp(a) PRS 和测量的 Lp(a) 显示出与动脉粥样硬化心血管疾病发病率相当的相关性，而 ApoB PRS 通常比测量的 ApoB 对动脉粥样硬化心血管疾病风险的预测更差。在欧洲心脏病学会/欧洲动脉粥样硬化学会血脂指南的背景下，以 95% 的灵敏度识别 Lp(a) 和 ApoB 水平升高的个体，