Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan; Department of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center Hospital, Suita, Japan; Cardiovascular Center, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan; Department of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; Department of Endocrinology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Atherosclerosis. 2022 Oct;358:41-46. doi: 10.1016/j.atherosclerosis.2022.08.014. Epub 2022 Aug 30.
Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL)-cholesterol, xanthoma of the Achilles tendon (AT), and premature coronary artery disease (CAD). Ultrasonography can assess AT thickness and softness, making it useful for evaluating AT in FH diagnosis. We aimed to clarify whether FH-causative LDLR or PCSK9 variants affect AT thickness or softness.
In total, 248 FH and 60 non-familial hypercholesterolemia (non-FH) patients (total: 308) aged ≥30 years were enrolled. Patients with FH were classified according to genotype. AT thickness and elasticity index (EI) as softness were measured by ultrasonography.
In FH patients with LDLR variants, AT was significantly thicker and softer than it was in FH patients with PCSK9 variants, FH patients without LDLR or PCSK9 variants, and patients with non-FH. The proportion of patients harboring LDLR variants significantly increased with AT thickness (p = 2.0 × 10) and softness (p = 1.4 × 10). Among those with AT thickness>8.5 mm and EI < 3.9, patients with LDLR variants accounted for 89% and 83%, respectively. The odds of AT thickening, AT softening and CAD increased 13.3-fold, 4.9-fold, and 2.1-fold, adjusted for the LDL-C year score by the presence of LDLR variants compared with those of patients without LDLR or PCSK9 variants. PCSK9 variants did not influence AT thickening or softening or CAD prevalence.
LDLR variants affected AT thickness and softness independent of the LDL-C year score, but PCSK9 variants did not. Evaluating AT is important for identifying FH patients with LDLR variants at high risk for CAD.
家族性高胆固醇血症（FH）的特征是低密度脂蛋白（LDL）-胆固醇水平升高、跟腱黄色瘤（AT）和早发冠心病（CAD）。超声检查可评估 AT 厚度和柔软度，有助于 FH 诊断中 AT 的评估。本研究旨在明确 FH 致病 LDLR 或 PCSK9 变异是否影响 AT 厚度和柔软度。
共纳入 248 例 FH 患者和 60 例非家族性高胆固醇血症（non-FH）患者（总计 308 例），年龄均≥30 岁。FH 患者根据基因型进行分类。通过超声检查测量 AT 厚度和弹性指数（EI）作为柔软度。
在 LDLR 变异的 FH 患者中，AT 厚度和柔软度均显著大于 PCSK9 变异的 FH 患者、无 LDLR 或 PCSK9 变异的 FH 患者和 non-FH 患者。携带 LDLR 变异的患者比例随 AT 厚度（p=2.0×10）和柔软度（p=1.4×10）增加而显著增加。在 AT 厚度>8.5mm 且 EI<3.9 的患者中，LDLR 变异的患者分别占 89%和 83%。与无 LDLR 或 PCSK9 变异的患者相比，存在 LDLR 变异时，AT 增厚、AT 变软和 CAD 的风险分别增加 13.3 倍、4.9 倍和 2.1 倍，校正 LDL-C 年积分后。PCSK9 变异不影响 AT 厚度或柔软度或 CAD 发生率。
LDLR 变异独立于 LDL-C 年积分影响 AT 厚度和柔软度，但 PCSK9 变异不影响。评估 AT 对识别 LDLR 变异的 FH 患者发生 CAD 的高风险很重要。
