Kjærgaard Kasper Aalbæk, Christiansen Morten Krogh, Schmidt Morten, Olsen Morten Smærup, Jensen Henrik Kjærulf
Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
J Am Heart Assoc. 2017 Jun 26;6(6):e005435. doi: 10.1161/JAHA.116.005435.
Heterozygous familial hypercholesterolemia increases the risk of adverse cardiovascular events. Whether affected relatives of probands are at increased risk remains unknown. We aimed to evaluate the long-term cardiovascular risk in heterozygous familial hypercholesterolemia relatives with a low-density lipoprotein receptor () mutation who were all recommended statin therapy.
Participants were identified by cascade screening at Aarhus University Hospital during 1992-1994. A comparison cohort from the Danish general population was matched 10:1 to relatives by birth year and sex. Using medical registries, participants were followed until the event of interest, migration, death, or end of follow-up on December 31, 2014. The primary end point was all-cause mortality and major adverse cardiovascular events comprising myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease, and coronary revascularization. We included 220 relatives. Median age was 37 years (interquartile range: 27-52 years) of which 118 (54%) had an mutation. By 2004, when prescription data became available, 89% of mutation-carrying participants were taking statins during their follow-up period. Despite frequent use of lipid-lowering medication, the adjusted hazard ratio of the primary end point was 1.65 (95% confidence interval, 1.17-2.33) in mutation-carrying relatives compared with the general population cohort. The risk in non-mutation-carrying relatives was not different from that of the general population cohort (adjusted hazard ratio: 0.85; 95% confidence interval, 0.56-1.29). Comparing mutation-carrying relatives with non-mutation-carrying relatives, the adjusted hazard ratio was 1.94 (95% confidence interval, 1.14-3.31). Results were driven by nonfatal events.
Heterozygous familial hypercholesterolemia relatives with an mutation had an increased long-term risk of adverse cardiovascular events.
杂合子家族性高胆固醇血症会增加不良心血管事件的风险。先证者的受影响亲属是否风险增加仍不清楚。我们旨在评估所有被推荐接受他汀类药物治疗的、携带低密度脂蛋白受体（）突变的杂合子家族性高胆固醇血症亲属的长期心血管风险。
1992年至1994年期间，在奥胡斯大学医院通过级联筛查确定参与者。丹麦普通人群的一个对照队列按出生年份和性别与亲属以10:1的比例匹配。利用医疗登记系统，对参与者进行随访，直至发生感兴趣的事件、迁移、死亡或2014年12月31日随访结束。主要终点是全因死亡率和主要不良心血管事件，包括心肌梗死、缺血性中风、短暂性脑缺血发作、外周动脉疾病和冠状动脉血运重建。我们纳入了220名亲属。中位年龄为37岁（四分位间距：27 - 52岁），其中118名（54%）携带突变。到2004年有处方数据可用时，89%携带突变的参与者在随访期间服用他汀类药物。尽管频繁使用降脂药物，但携带突变的亲属与普通人群队列相比，主要终点的调整后风险比为1.65（95%置信区间，1.17 - 2.33）。非携带突变亲属的风险与普通人群队列无异（调整后风险比：0.85；95%置信区间，0.56 - 1.29）。将携带突变的亲属与非携带突变的亲属进行比较，调整后风险比为1.94（95%置信区间，1.14 - 3.31）。结果由非致命事件驱动。
携带突变的杂合子家族性高胆固醇血症亲属发生不良心血管事件的长期风险增加。
