Shishikura Daisuke, Harada-Shiba Mariko, Michikura Masahito, Fujioka Shimpei, Fujisaka Tomohiro, Morita Hideaki, Kanzaki Yumiko, Hoshiga Masaaki
Department of Cardiology, Osaka Medical and Pharmaceutical University.
J Atheroscler Thromb. 2025 Jan 1;32(1):100-110. doi: 10.5551/jat.65009. Epub 2024 Aug 6.
Elevated lipoprotein (a) (Lp[a]), predominantly determined by genetic variability, causes atherosclerotic cardiovascular disease (ASCVD), particularly in patients with familial hypercholesterolemia (FH). We aimed to elucidate the clinical impact of Lp(a) and cumulative exposure to low-density lipoprotein cholesterol (LDL-C) on CAD in patients with FH.
One hundred forty-seven patients clinically diagnosed with heterozygous familial hypercholesterolemia (HeFH) were retrospectively investigated. Patients were divided into 2 groups according to the presence of CAD. Their clinical characteristics and lipid profiles were evaluated.
There were no significant differences in untreated LDL-C levels between the 2 groups (p=0.4), whereas the cumulative exposure to LDL-C and Lp(a) concentration were significantly higher in patients with CAD (11956 vs. 8824 mg-year/dL, p＜0.01; 40 vs. 14 mg/dL, p＜0.001, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated that the cutoff values of Lp(a) and cumulative LDL-C exposure to predict CAD in patients with FH were 28 mg/dL (AUC 0.71) and 10600 mg-year/dL (AUC 0.77), respectively. A multivariate analysis revealed that cumulative LDL-C exposure ≥ 10600 mg-year/dL (p＜0.0001) and Lp(a) level ≥ 28 mg/dL (p＜0.001) were independent predictors of CAD. Notably, the risk of CAD remarkably increased to 85.7% with smoking, Lp(a) ≥ 28 mg/dL, and cumulative LDL-C exposure ≥ 10600 mg-year/dL (odds ratio: 46.5, 95%CI: 5.3-411.4, p＜0.001).
This study demonstrated an additive effect of Lp(a) and cumulative LDL-C exposure on CAD in patients with HeFH. Interaction with traditional risk factors, particularly smoking and cumulative LDL-C exposure, enormously enhances the cardiovascular risk in this population.
脂蛋白(a)[Lp(a)]升高主要由基因变异决定，可导致动脉粥样硬化性心血管疾病(ASCVD)，尤其是在家族性高胆固醇血症(FH)患者中。我们旨在阐明Lp(a)和低密度脂蛋白胆固醇(LDL-C)的累积暴露对FH患者冠心病(CAD)的临床影响。
对147例临床诊断为杂合子家族性高胆固醇血症(HeFH)的患者进行回顾性研究。根据是否患有CAD将患者分为两组。评估他们的临床特征和血脂谱。
两组患者未经治疗的LDL-C水平无显著差异(p = 0.4)，而CAD患者的LDL-C累积暴露量和Lp(a)浓度显著更高(分别为11956 vs. 8824 mg-年/dL，p＜0.01；40 vs. 14 mg/dL，p＜0.001)。受试者工作特征(ROC)曲线分析表明，预测FH患者CAD的Lp(a)和LDL-C累积暴露的临界值分别为28 mg/dL(AUC 0.71)和10600 mg-年/dL(AUC 0.77)。多变量分析显示，LDL-C累积暴露≥10600 mg-年/dL(p＜0.0001)和Lp(a)水平≥28 mg/dL(p＜0.001)是CAD的独立预测因素。值得注意的是，吸烟、Lp(a)≥28 mg/dL和LDL-C累积暴露≥10600 mg-年/dL时，CAD风险显著增加至85.7%(优势比：46.5，95%CI：5.3-411.4，p＜0.001)。
本研究证明了Lp(a)和LDL-C累积暴露对HeFH患者CAD具有相加作用。与传统危险因素的相互作用，尤其是吸烟和LDL-C累积暴露，极大地增加了该人群的心血管风险。
