Research Institute of the McGill University Health Centre, 1001, Boul. Décarie, Office EM1.2212, Montréal, Québec, Canada.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Eur Heart J. 2022 Sep 7;43(34):3227-3239. doi: 10.1093/eurheartj/ehac339.
Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565).
MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted.
These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients.
家族性高胆固醇血症（HoFH）是一种孤儿病，其特征为低密度脂蛋白胆固醇极度升高、皮肤黄色瘤和早发动脉粥样硬化性心血管疾病。在过去的三十年中，患者的存活率增加了一倍以上。常合并主动脉瓣狭窄（AS）[主动脉瓣上狭窄（SVAS）或主动脉瓣狭窄（VAS）]。目前尚无有效的治疗方法，复杂的高危手术是严重情况下的唯一选择。本系统评价旨在总结目前 HoFH 患者 AS 的证据，并确定过去 90 年中（PROSPERO CRD42021250565），药物治疗（他汀类药物）是否对临床表现、表型和临床病程产生了影响。
从建库到 2021 年 11 月 10 日，检索 MEDLINE、Embase Classic+Embase、Cochrane 中央对照试验注册库、PubMed、AfricaWide 和 Scopus。检索到 381 篇文献，其中 19 篇被保留；这些研究为横断面或回顾性研究。此外，还描述了 108 例单独的病例报告。在 424 例 HoFH 患者中，他汀类药物问世前，AS 见于 57%的患者，而最近（>2000 年，他汀类药物长期治疗期）报道的患者中 AS 见于 35%。由于他汀类药物和脂蛋白吸附治疗延长了患者的寿命，SVAS 和 VAS 的患者比例发生了变化，未接受他汀类药物和长期接受他汀类药物治疗的 HoFH 患者的 SVAS：VAS 比值分别为 47:53 和 10:90。
这些数据表明，SVAS 和 VAS 在 HoFH 中很常见，并且随着他汀类药物和脂蛋白吸附治疗改善了这些患者的生存率，表型已向钙化性 VAS 转变。
