载脂蛋白(a)对冠状动脉疾病多基因风险预测的贡献：一项英国生物库前瞻性分析。

Contribution of Lipoprotein(a) to Polygenic Risk Prediction of Coronary Artery Disease: A Prospective UK Biobank Analysis.

机构信息

Centre de recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec (H.D.M., A.P., A.G., A.E., P.M., S.T., B.J.A.), Faculty of Medicine, Université Laval, Québec (QC), Canada.

Department of Social and Preventive Medicine (A.E.), Faculty of Medicine, Université Laval, Québec (QC), Canada.

出版信息

Circ Genom Precis Med. 2023 Oct;16(5):470-477. doi: 10.1161/CIRCGEN.123.004137. Epub 2023 Sep 27.

DOI:10.1161/CIRCGEN.123.004137

PMID:37753708

Abstract

BACKGROUND

Lp(a) (lipoprotein[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD.

METHODS

A total of 372 385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using the LDpred2 algorithm. Over the median follow-up of 12.6 years, 13 538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting, or coronary angioplasty).

RESULTS

The region contribution to the CAD-PRS-mediated CAD risk was modest (7.2% [95% CI, 6.1-8.3]). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C statistic 0.751 versus 0.746, difference, 0.005 [95% CI, 0.004-0.006]). Compared with participants in the bottom CAD-PRS quintile with Lp(a) levels <25 nmol/L (CAD event rate, 1.4%), the hazard ratio for incident CAD in participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L was 5.45 (95% CI, 4.93-6.03; =9.35×10, CAD event rate 6.6%).

CONCLUSIONS

Compared with individuals with a low genetic risk of CAD (low CAD-PRS and low Lp[a] levels), those with a high genetic risk (high CAD-PRS and high Lp[a] levels) had a 5-fold higher CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD may need to consider blood levels of Lp(a).

摘要

背景

脂蛋白(a)（Lp(a)）是一种高度致动脉粥样硬化的脂蛋白亚群，可能导致冠心病（CAD）的多基因风险，但这种贡献的程度尚不清楚。我们的目的是估计 Lp(a) 对 CAD 多基因风险的贡献，并评估 Lp(a)和 CAD 多基因风险评分（PRS）对 CAD 的各自贡献。

方法

共纳入 372385 名无 CAD 的英国生物库欧洲血统的参与者。测量血浆 Lp(a)水平，并使用 LDpred2 算法计算 CAD-PRS。在中位随访 12.6 年期间，有 13538 名参与者发生了 CAD（心肌梗死、冠状动脉旁路移植术或冠状动脉血管成形术）。

结果

该区域对 CAD-PRS 介导的 CAD 风险的贡献适中（7.2%[95%CI，6.1-8.3]）。Lp(a)水平在 Cox 回归中显著提高了包括年龄和性别在内的 CAD-PRS 的预测性能（C 统计量 0.751 与 0.746 相比，差异为 0.005[95%CI，0.004-0.006]）。与 CAD-PRS 五分位最低且 Lp(a)水平<25 nmol/L 的参与者（CAD 事件发生率为 1.4%）相比，CAD-PRS 五分位最高且 Lp(a)水平≥125 nmol/L 的参与者发生 CAD 的风险比为 5.45（95%CI，4.93-6.03；=9.35×10，CAD 事件发生率为 6.6%）。