Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego, La Jolla, California, USA.
Medpace Reference Laboratories, Cincinnati, Ohio, USA.
J Am Coll Cardiol. 2022 Aug 30;80(9):934-946. doi: 10.1016/j.jacc.2022.06.019.
This study reviews ancestral differences in the genetics of the LPA gene, risk categories of elevated lipoprotein(a) [Lp(a)] as defined by guidelines, ancestry-specific Lp(a) risk, absolute and proportional risk, predictive value of risk thresholds among different ancestries, and differences between laboratory vs clinical accuracy in Lp(a) assays. For clinical decision-making, the preponderance of evidence suggests that the predictive value of Lp(a) does not vary sufficiently to mandate the use of ancestry-specific risk thresholds. This paper interprets the literature on Lp(a) and ancestral risk to support: 1) clinicians on understanding cardiovascular disease risk in different ancestral groups; 2) trialists for the design of clinical trials to ensure adequate ancestral diversity to support broad conclusions of drug effects; 3) regulators in the evaluation of the design and interpretation of results of Lp(a)-lowering trials with different Lp(a) inclusion thresholds; and 4) clinical laboratories to measure Lp(a) by assays that discriminate risk thresholds appropriately.
本研究回顾了 LPA 基因遗传的祖先差异、指南定义的升高脂蛋白(a) [Lp(a)]的风险类别、特定祖先的 Lp(a)风险、绝对风险和相对风险、不同祖先群体中风险阈值的预测值，以及实验室与临床 Lp(a)检测的准确性差异。对于临床决策，大量证据表明，Lp(a)的预测价值没有足够的差异，需要使用特定祖先的风险阈值。本文解读了关于 Lp(a)和祖先风险的文献，以支持：1) 临床医生了解不同祖先群体的心血管疾病风险；2) 试验设计者为确保药物效果的广泛结论，进行临床试验设计，确保足够的祖先多样性；3) 监管机构在评估不同 Lp(a)纳入阈值的 Lp(a)降低试验的设计和解释时；4) 临床实验室通过适当区分风险阈值的检测方法来测量 Lp(a)。
