Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Atherosclerosis. 2021 Jul;329:22-29. doi: 10.1016/j.atherosclerosis.2021.06.004. Epub 2021 Jun 11.
Lipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific.
In 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics.
Lipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44).
In patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.
脂蛋白(a)是心血管疾病和复发性缺血性中风的独立危险因素。已知脂蛋白(a)水平与颈动脉狭窄有关，但脂蛋白(a)水平与颈动脉粥样硬化斑块成分和形态的关系知之甚少。我们假设较高的脂蛋白(a)水平和脂蛋白(a)相关的 SNP 与更易损的颈动脉斑块有关，而且这种影响具有性别特异性。
在 Plaque At RISK 研究的 182 例患者中，我们测定了脂蛋白(a)浓度、载脂蛋白(a) KIV-2 重复和 LPA SNP。通过 MDCTA(n=161)和/或 MRI(n=171)确定颈动脉粥样硬化的影像学特征。回归分析用于研究脂蛋白(a)水平、载脂蛋白(a) KIV-2 重复和 LPA SNP 与影像学特征之间的性别分层关联。
脂蛋白(a)与富含脂质的坏死核心(LRNC)的存在相关(aOR=1.07，95%CI：1.00；1.15)，薄或破裂的纤维帽(TRFC)(aOR=1.07，95%CI：1.01；1.14)和狭窄程度(β=0.44，95%CI：0.00；0.88)。在女性中，脂蛋白(a)与斑块内出血(IPH)的存在相关(aOR=1.25，95%CI：1.06；1.61)。在男性中，脂蛋白(a)与狭窄程度相关(β=0.58，95%CI：0.04；1.12)。rs10455872 与钙化体积增加显著相关(β=1.07，95%CI：0.25；1.89)，与斑块溃疡缺失相关(aOR=0.25，95%CI：0.04；0.93)。T3888P 与 LRNC 缺失相关(aOR=0.36，95%CI：0.16；0.78)和最大血管壁面积较小相关(β=-10.24，95%CI：-19.03；-1.44)。
在有症状的颈动脉狭窄患者中，脂蛋白(a)水平升高与狭窄程度以及颈动脉易损斑块特征的 IPH、LRNC 和 TRFC 相关。T3888P 与较低的 LRNC 患病率和较小的最大血管壁面积相关。需要在更大的研究人群中进一步研究以证实这些结果。
