Department of Radiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Interuniversitair Cardiologisch Instituut Nederland, Utrecht, the Netherlands; Department of Cardiology, Thorax Centre Rotterdam, Rotterdam, the Netherlands.
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam, the Netherlands.
J Am Coll Cardiol. 2015 Dec 22;66(24):2687-2695. doi: 10.1016/j.jacc.2015.09.087.
Familial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic.
The objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown.
Asymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC).
We included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9-117); and 21%, 21 (3-49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001).
Compared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology.
家族性高胆固醇血症通常由 LDL 受体 (LDLR) 突变引起，导致 LDL 胆固醇 (LDL-C) 水平升高。在纯合子 FH 中，主动脉瓣钙化 (AoVC) 的患病率达到 100%，且常伴有症状。
本研究旨在调查目前尚不清楚的杂合子 FH (he-FH) 患者中 AoVC 的患病率、程度和风险修饰因子。
无症状的 he-FH 患者和 131 名非家族性高胆固醇血症对照者接受 CT 计算机断层扫描钙评分。AoVC 定义为主动脉瓣叶有钙存在。AoVC 的程度用 Agatston 单位表示，即 AoVC 评分。我们比较了病例组和对照组之间 AoVC 的患病率和程度。此外，我们还研究了 AoVC 的风险修饰因子，包括 LDLR 无残留功能的突变（LDLR 阴性突变）、最大未治疗 LDL-胆固醇（maxLDL）、LDL-C、血压和冠状动脉钙化（CAC）。
我们纳入了 145 名无症状的 he-FH 患者（93 名男性；平均年龄 52±8 岁）和 131 名非家族性高胆固醇血症对照者。he-FH 患者的患病率（%）和 AoVC 评分（中位数，IQR）均高于对照组：41%，51（9-117）；21%，21（3-49）（p<0.001 和 p=0.007）。年龄、未治疗的 maxLDL、CAC 和舒张压与 AoVC 独立相关。LDLR 阴性突变的 he-FH 是 AoVC 评分的最强预测因子（OR：4.81；95%CI：2.22 至 10.40；p<0.001）。
与对照组相比，he-FH 与亚临床 AoVC 的高患病率和大程度相关，尤其是在 LDLR 阴性突变患者中，这突出了 LDL-C 代谢在 AoVC 病因学中的关键作用。
