School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia; School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia.
Cardiology Department, Hospital Clínico San Carlos, IDISSC, Universidad Complutense, Madrid, Spain; Fundación Hipercolesterolemia Familiar, Madrid, Spain.
J Am Coll Cardiol. 2019 Mar 12;73(9):1029-1039. doi: 10.1016/j.jacc.2018.12.037.
Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a).
This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program.
Family members (N = 2,927) from 755 index cases enrolled in SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) were tested for genetic FH and elevated Lp(a) via an established screening program. Elevated Lp(a) was defined as levels ≥50 mg/dl. The authors compared the prevalence and yield of new cases of high Lp(a) in relatives of FH probands both with and without high Lp(a), and prospectively investigated the association between elevated Lp(a) and ASCVD events among family members.
Systematic screening from index cases with both FH and elevated Lp(a) identified 1 new case of elevated Lp(a) for every 2.4 screened. Opportunistic screening from index cases with FH, but without elevated Lp(a), identified 1 individual for 5.8 screened. Over 5 years' follow-up, FH (hazard ratio [HR]: 2.47; p = 0.036) and elevated Lp(a) (HR: 3.17; p = 0.024) alone were associated with a significantly increased risk of experiencing an ASCVD event or death compared with individuals with neither disorder; the greatest risk was observed in relatives with both FH and elevated Lp(a) (HR: 4.40; p < 0.001), independent of conventional risk factors.
Testing for elevated Lp(a) during cascade screening for FH is effective in identifying relatives with high Lp(a) and heightened risk of ASCVD, particularly when the proband has both FH and elevated Lp(a).
家族性高胆固醇血症（FH）和脂蛋白（a）[Lp(a)]升高是与早发动脉粥样硬化性心血管疾病（ASCVD）相关的遗传性疾病。FH 推荐进行级联检测，但对于 Lp(a)升高尚无类似的推荐。
本研究旨在探讨在 FH 级联筛查项目中检测 Lp(a)是否能有效发现并对个体进行风险分层。
755 例 FH 先证者的家族成员（N=2927）参加了 SAFEHEART（西班牙家族性高胆固醇血症队列研究），通过已建立的筛查方案对其进行 FH 和 Lp(a)升高的基因检测。Lp(a)升高定义为水平≥50mg/dl。作者比较了 FH 先证者及其无 Lp(a)升高亲属中高 Lp(a)新发病例的患病率和检出率，并前瞻性研究了 Lp(a)升高与家族成员 ASCVD 事件之间的关联。
FH 合并 Lp(a)升高的先证者进行系统性筛查，每筛查 2.4 人即可发现 1 例新的 Lp(a)升高患者。FH 先证者进行机会性筛查，且无 Lp(a)升高，每筛查 5.8 人即可发现 1 例。在 5 年的随访中，FH（危险比[HR]：2.47；p=0.036）和 Lp(a)升高（HR：3.17；p=0.024）单独与 ASCVD 事件或死亡风险显著增加相关，与既无 FH 也无 Lp(a)升高的个体相比；风险最大的是同时患有 FH 和 Lp(a)升高的亲属（HR：4.40；p<0.001），独立于传统危险因素。
在 FH 级联筛查中检测 Lp(a)，可有效识别 Lp(a)升高且 ASCVD 风险增加的亲属，尤其是当先证者同时患有 FH 和 Lp(a)升高时。
