Genetically predicted lipoprotein(a) associates with coronary artery plaque severity independent of low-density lipoprotein cholesterol.

IF 8.4 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European journal of preventive cardiology Pub Date : 2025-01-27 DOI:10.1093/eurjpc/zwae271
Shoa L Clarke, Rose D L Huang, Austin T Hilliard, Michael G Levin, Disha Sharma, Blake Thomson, Julie Lynch, Philip S Tsao, J Michael Gaziano, Themistocles L Assimes
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Abstract

Aims: Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease, but the mechanisms of risk are debated. Studies have found inconsistent associations between Lp(a) and measurements of atherosclerosis. We aimed to assess the relationship between Lp(a), low-density lipoprotein cholesterol (LDL-C), and coronary artery plaque severity.

Methods and results: The study population consisted of participants of the Million Veteran Program who have undergone an invasive angiogram. The primary exposure was genetically predicted Lp(a) estimated by a polygenic score. Genetically predicted LDL-C was also assessed for comparison. The primary outcome was coronary artery plaque severity categorized as normal, non-obstructive disease, one-vessel disease, two-vessel disease, and three-vessel or left main disease. Among 18 927 adults of genetically inferred European ancestry and 4039 adults of genetically inferred African ancestry, we observed consistent associations between genetically predicted Lp(a) and obstructive coronary plaque, with effect sizes trending upward for increasingly severe categories of disease. Associations were independent of risk factors, clinically measured LDL-C and genetically predicted LDL-C. However, we did not find strong or consistent evidence for an association between genetically predicted Lp(a) and risk for non-obstructive plaque.

Conclusion: Genetically predicted Lp(a) is positively associated with coronary plaque severity independent of LDL-C, consistent with Lp(a) promoting atherogenesis. However, the effects of Lp(a) may be greater for progression of plaque to obstructive disease than for the initial development of non-obstructive plaque. A limitation of this study is that Lp(a) was estimated using genetic markers and could not be directly assayed nor could apo(a) isoform size.

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基因预测的脂蛋白(a)与冠状动脉斑块严重程度的关系与低密度脂蛋白胆固醇无关。
目的:脂蛋白(a)[Lp(a)]升高是动脉粥样硬化性心血管疾病的致病风险因素,但其风险机制尚存在争议。研究发现,脂蛋白(a)与动脉粥样硬化测量值之间的关系并不一致。我们旨在评估脂蛋白(a)、低密度脂蛋白胆固醇(LDL-C)和冠状动脉斑块严重程度之间的关系:研究对象包括接受过侵入性血管造影检查的 "百万退伍军人计划 "参与者。主要暴露因子是通过多基因评分估算的基因预测脂蛋白(a)。同时还评估了基因预测的低密度脂蛋白胆固醇(LDL-C),以进行比较。主要结果是冠状动脉斑块严重程度,分为正常、非阻塞性疾病、1血管疾病、2血管疾病、3血管或左主干疾病:在18927名经基因推断具有欧洲血统的成年人和4039名经基因推断具有非洲血统的成年人中,我们观察到基因预测的脂蛋白(a)与阻塞性冠状动脉斑块之间存在一致的关联,随着疾病类别的增加,效应大小呈上升趋势。这种关联与风险因素、临床测量的低密度脂蛋白胆固醇和基因预测的低密度脂蛋白胆固醇无关。但是,我们没有发现基因预测的脂蛋白(a)与非阻塞性斑块风险之间存在关联的有力或一致的证据:结论:基因预测的脂蛋白(a)与冠状动脉斑块的严重程度呈正相关,与低密度脂蛋白胆固醇无关,这与脂蛋白(a)促进动脉粥样硬化是一致的。然而,脂蛋白(a)对斑块进展为阻塞性疾病的影响可能大于对非阻塞性斑块初期发展的影响。这项研究的局限性在于,脂蛋白(a)是通过基因标记物估算的,无法直接测定,载脂蛋白(a)同工酶的大小也是如此。
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来源期刊
European journal of preventive cardiology
European journal of preventive cardiology CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
12.50
自引率
12.00%
发文量
601
审稿时长
3-8 weeks
期刊介绍: European Journal of Preventive Cardiology (EJPC) is an official journal of the European Society of Cardiology (ESC) and the European Association of Preventive Cardiology (EAPC). The journal covers a wide range of scientific, clinical, and public health disciplines related to cardiovascular disease prevention, risk factor management, cardiovascular rehabilitation, population science and public health, and exercise physiology. The categories covered by the journal include classical risk factors and treatment, lifestyle risk factors, non-modifiable cardiovascular risk factors, cardiovascular conditions, concomitant pathological conditions, sport cardiology, diagnostic tests, care settings, epidemiology, pharmacology and pharmacotherapy, machine learning, and artificial intelligence.
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