目的:脂蛋白(a)[Lp(a)]升高是动脉粥样硬化性心血管疾病的因果危险因素,但是风险机制是有争议的。研究发现Lp(a)与动脉粥样硬化的测量之间存在不一致的关联。我们的目的是评估Lp(a),低密度脂蛋白胆固醇(LDL-C)与冠状动脉斑块严重程度。
方法:研究人群由接受过侵入性血管造影的百万退伍军人计划的参与者组成。主要暴露是遗传预测的Lp(a),通过多基因评分估计。还评估了遗传预测的LDL-C用于比较。主要结果是冠状动脉斑块严重程度,归类为正常,非阻塞性疾病,1血管疾病,2血管疾病,和3血管或左主要疾病。
结果:在18,927名具有遗传推断的欧洲血统的成年人和4,039名具有遗传推断的非洲血统的成年人中,我们观察到基因预测的Lp(a)和阻塞性冠状动脉斑块之间的一致关联,对于越来越严重的疾病类别,效应大小呈上升趋势。关联独立于危险因素,临床测量的LDL-C和遗传预测的LDL-C。然而,我们没有发现基因预测的Lp(a)与非阻塞性斑块风险相关的有力或一致的证据.
结论:遗传预测Lp(a)与冠状动脉斑块严重程度呈正相关,与LDL-C无关,与Lp(a)促进动脉粥样硬化一致。然而,Lp(a)对斑块进展为阻塞性疾病的影响可能大于对初始发展为非阻塞性斑块的影响。这项研究的局限性在于Lp(a)是使用遗传标记进行估计的,无法直接测定,apo(a)也不能同工型大小。
本研究评估了血液中更高脂蛋白(a)[Lp(a)]的遗传倾向与临床血管造影上看到的冠状动脉斑块严重程度之间的关联。独立于其他因素,包括低密度脂蛋白胆固醇(LDL-C)。这项研究是在美国大量人口中使用百万退伍军人计划的数据进行的。遗传预测的高Lp(a)与阻塞性冠状动脉斑块相关,但与非阻塞性冠状动脉斑块无关.这种关联与LDL-C无关,对于更严重的疾病形式,这种关联更大。Lp(a)与心血管事件之间的关联机制存在争议。先前的研究表明,Lp(a)与动脉粥样硬化的早期标志物无关。我们的分析支持Lp(a)在早期斑块启动中的作用较小,但在斑块向更严重疾病的进展中起重要作用的观点。与LDL-C无关
OBJECTIVE: 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: 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, 1-vessel disease, 2-vessel disease, and 3-vessel or left main disease.
RESULTS: Among 18,927 adults of genetically inferred European ancestry and 4,039 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.
CONCLUSIONS: 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.
This study assessed the association between genetic propensity towards higher lipoprotein(a) [Lp(a)] in the blood and the severity of coronary artery plaque seen on clinical angiograms, independent of other factors, including low-density lipoprotein cholesterol (LDL-C). The study was conducted in a large U.S. population using data from the Million Veteran Program. Genetically predicted high Lp(a) was associated with obstructive coronary plaque, but it was not associated with non-obstructive coronary plaque. This association was independent of LDL-C, and the association was greater for more severe forms of disease.The mechanisms of association between Lp(a) and cardiovascular events are debated. Prior studies have shown that Lp(a) does not associate with early markers of atherosclerosis. Our analyses support the idea that Lp(a) plays less of a role in early plaque initiation but plays a significant role in the progression of plaque towards more severe disease, independent of LDL-C.