Cardiology Department, Hospital Clínico San Carlos, IDISSC, Facultad de Medicina, Universidad Complutense, C/Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Fundación Hipercolesterolemia Familiar, C/General Alvarez de Castro 14, 28010 Madrid, Spain.
Eur J Prev Cardiol. 2022 May 5;29(5):795-801. doi: 10.1093/eurjpc/zwab185.
Knowledge of the features of patients with familial hypercholesterolaemia (FH) who are protected from atherosclerotic cardiovascular disease (ASCVD) is important for the clinical and prognostic care of this apparently high-risk condition. Our aim was to investigate the determinant and characteristics of patients with FH who are protected from ASCVD and have normal life expectancy, so-called 'resilient' FH (R-FH).
Spanish Familial Hypercholesterolaemia cohort study (SAFEHEART) is an open, multicentre, nation-wide, long-term prospective cohort study in genetically defined patients with heterozygous FH in Spain. Patients in the registry who at the time of analysis were at least 65 years or those who would have reached that age had they not died from an ASCVD event were analysed as a case-control study. Resilient FH was defined as the presence of a pathogenic mutation causative of FH in a patient aged ≥65 years without clinical ASCVD. Nine hundred and thirty registrants with FH met the study criteria. A defective low-density lipoprotein (LDL)-receptor mutation, higher plasma level of high-density lipoprotein cholesterol (HDL-C), younger age, female gender, absence of hypertension, and lower plasma lipoprotein (a) [Lp(a)] concentration were independently predictive of R-FH. In a second model, higher levels of HDL-C and lower 10-year score in SAFEHEART-RE were also independently predictive of R-FH.
Resilient FH may be typified as being female and having a defective LDL-receptor mutation, higher levels of plasma HDL-C, lower levels of Lp(a), and an absence of hypertension. The implications of this type of FH for clinical practice guidelines and the value for service design and optional care of FH remains to be established.
ClinicalTrials.gov number NCT02693548.
了解家族性高胆固醇血症（FH）患者中未发生动脉粥样硬化性心血管疾病（ASCVD）的个体的特征，对于此类高危人群的临床和预后管理具有重要意义。本研究旨在探讨 FH 患者中发生 ASCVD 风险低且预期寿命正常的个体（所谓“韧性 FH”）的决定因素和特征。
西班牙 FH 队列研究（SAFEHEART）是一项在西班牙开展的、针对携带杂合子 FH 致病基因突变的患者、开放性、多中心、全国性、长期前瞻性队列研究。本研究对该登记处中在分析时至少 65 岁或在未死于 ASCVD 事件的情况下本应达到该年龄的患者进行了病例对照研究。定义韧性 FH 为 65 岁以上且无 ASCVD 临床证据的 FH 患者存在致病性 LDL 受体突变。符合研究标准的 930 例 FH 患者中，有 368 例为韧性 FH。携带 LDL 受体缺陷型突变、高密度脂蛋白胆固醇（HDL-C）水平较高、年龄较小、女性、无高血压、脂蛋白（a）[Lp（a）]浓度较低与韧性 FH 独立相关。在第二个模型中，HDL-C 水平较高和 SAFEHEART-RE 10 年评分较低也与韧性 FH 独立相关。
韧性 FH 可能的特征是女性、存在 LDL 受体缺陷型突变、HDL-C 水平较高、Lp（a）水平较低且无高血压。这种 FH 对临床实践指南的意义以及 FH 服务设计和可选护理的价值仍有待确定。
ClinicalTrials.gov 编号 NCT02693548。
