Center for Genomic Medicine (A.P.P., J.P.P., P.T.E., A.V.K.), Massachusetts General Hospital, Boston.
Division of Cardiology, Department of Medicine (A.P.P., J.P.P., P.T.E., S.K., A.V.K.), Massachusetts General Hospital, Boston.
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):465-474. doi: 10.1161/ATVBAHA.120.315291. Epub 2020 Oct 29.
Lp(a) (lipoprotein[a]) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are in development. In the largest study conducted to date, we address 3 areas of uncertainty: (1) the magnitude and shape of ASCVD risk conferred across the distribution of lipoprotein(a) concentrations; (2) variation of risk across racial and clinical subgroups; (3) clinical importance of a high lipoprotein(a) threshold to guide therapy. Approach and Results: Relationship of lipoprotein(a) to incident ASCVD was studied in 460 506 middle-aged UK Biobank participants. Over a median follow-up of 11.2 years, incident ASCVD occurred in 22 401 (4.9%) participants. Median lipoprotein(a) concentration was 19.6 nmol/L (25th-75th percentile 7.6-74.8). The relationship between lipoprotein(a) and ASCVD appeared linear across the distribution, with a hazard ratio of 1.11 (95% CI, 1.10-1.12) per 50 nmol/L increment. Substantial differences in concentrations were noted according to race-median values for white, South Asian, black, and Chinese individuals were 19, 31, 75, and 16 nmol/L, respectively. However, risk per 50 nmol/L appeared similar-hazard ratios of 1.11, 1.10, and 1.07 for white, South Asian, and black individuals, respectively. A high lipoprotein(a) concentration defined as ≥150 nmol/L was present in 12.2% of those without and 20.3% of those with preexisting ASCVD and associated with hazard ratios of 1.50 (95% CI, 1.44-1.56) and 1.16 (95% CI, 1.05-1.27), respectively.
Lipoprotein(a) concentrations predict incident ASCVD among middle-aged adults within primary and secondary prevention contexts, with a linear risk gradient across the distribution. Concentrations are variable across racial subgroups, but the associated risk appears similar.
脂蛋白(a)[Lp(a)]浓度与动脉粥样硬化性心血管疾病（ASCVD）相关，目前正在开发能够实现强效且特异性降低 Lp(a)的新疗法。在迄今为止进行的最大规模研究中，我们解决了以下 3 个不确定性问题：（1）Lp(a)浓度分布范围内，ASCVD 风险的幅度和形状；（2）不同种族和临床亚组之间的风险差异；（3）指导治疗的高脂蛋白(a)阈值的临床重要性。方法和结果：在英国生物库 460506 名中年参与者中，研究了脂蛋白(a)与 ASCVD 发病的关系。中位随访 11.2 年后，22401 名（4.9%）参与者发生 ASCVD。脂蛋白(a)的中位数浓度为 19.6nmol/L（25%-75%分位数为 7.6-74.8）。脂蛋白(a)与 ASCVD 的关系呈线性分布，每增加 50nmol/L，风险比为 1.11（95%CI，1.10-1.12）。根据种族，脂蛋白(a)浓度存在显著差异，白种人、南亚人、黑人和中国人的中位值分别为 19、31、75 和 16nmol/L。然而，每 50nmol/L 的风险似乎相似-白种人、南亚人和黑人的风险比分别为 1.11、1.10 和 1.07。无预先存在 ASCVD 的参与者中，脂蛋白(a)浓度≥150nmol/L 的比例为 12.2%，而预先存在 ASCVD 的参与者中这一比例为 20.3%，相应的风险比分别为 1.50（95%CI，1.44-1.56）和 1.16（95%CI，1.05-1.27）。结论：在一级和二级预防环境中，脂蛋白(a)浓度可预测中年人群的 ASCVD 发病风险，呈线性分布。在不同种族亚组中，浓度存在差异，但相关风险似乎相似。
