Intra-individual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate risk.

European heart journal open Pub Date : 2024-08-31 eCollection Date: 2024-09-01 DOI:10.1093/ehjopen/oeae064
Tarek Harb, Efthymios Ziogos, Roger S Blumenthal, Gary Gerstenblith, Thorsten M Leucker
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Abstract

Aims: Lipoprotein(a) [Lp(a)] levels are predominantly genetically determined and repeat measurements are generally considered unlikely to be clinically useful. However, the temporal variation of Lp(a) is not well characterized. Our aim was to determine the intra-individual variability of Lp(a) and whether a repeated measure reclassified Lp(a)-specific cardiovascular risk using the European Atherosclerosis Society (EAS) consensus statement risk categories.

Methods and results: This retrospective cohort study analysed initial and repeated serum Lp(a) levels measured using the same methodology from 609 individuals in the Nashville Biosciences database, a de-identified electronic medical records database. Baseline and follow-up paired values were significantly different (P < 0.05), with an absolute change of ≥10 mg/dL in 38.1% [95% CI 34.2-42%] and a >25% change in 40.5% [95% CI 36.6-44.3%] of individuals. Although the categories of those whose values were in the EAS low-risk and high-risk categories did not change, 53% of those in the intermediate 'grey-zone' category transitioned to either the low-risk (20%) or high-risk (33%) category. Black individuals exhibited greater variability than White individuals and women exhibited greater variability than men. There was a positive correlation between the baseline Lp(a) levels and the absolute changes in Lp(a), (r = 0.59, P < 0.01).

Conclusion: Temporal-related changes in Lp(a) variability were present in many individuals. A repeat Lp(a) measure may allow more precise Lp(a)-specific cardiovascular risk prediction for individuals whose initial value is in the EAS-defined intermediate 'grey-zone' category. Lp(a) variability should be included in calculating the expected effect sizes in future clinical research studies targeting Lp(a).

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脂蛋白(a)的个体内变异性:重复测量对中危个体重新分类的价值。
目的:脂蛋白(a)[Lp(a)]水平主要由基因决定,一般认为重复测量不会对临床有用。然而,脂蛋白(a)的时间变化特征并不明显。我们的目的是确定脂蛋白(a)的个体内变异性,以及重复测量是否能根据欧洲动脉粥样硬化协会(EAS)共识声明的风险类别对脂蛋白(a)特异性心血管风险进行重新分类:这项回顾性队列研究分析了纳什维尔生物科学数据库(一个去标识化的电子病历数据库)中使用相同方法测量的 609 人的初始和重复血清脂蛋白(a)水平。基线值和随访配对值有显著差异(P < 0.05),38.1% [95% CI 34.2-42%]的人绝对值变化≥10 mg/dL,40.5% [95% CI 36.6-44.3%]的人变化>25%。虽然处于 EAS 低风险和高风险类别的人的类别没有发生变化,但处于中间 "灰色地带 "类别的人中有 53% 过渡到了低风险(20%)或高风险(33%)类别。黑人的变异性大于白人,女性的变异性大于男性。Lp(a) 的基线水平与 Lp(a) 的绝对变化呈正相关(r = 0.59,P < 0.01):结论:许多人的脂蛋白(a)变异性存在与时间相关的变化。对于初始值处于 EAS 界定的中间 "灰色区域 "类别的个体,重复测量 Lp(a)可更准确地预测 Lp(a)特异性心血管风险。在未来针对脂蛋白(a)的临床研究中,计算预期效应大小时应将脂蛋白(a)变异性包括在内。
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