Cardiovascular manifestations in men and women carrying a FBN1 mutation
Cardiovascular manifestations in men and women carrying a FBN1 mutation
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DOI：
10.1093/eurheartj/ehq258
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发表时间：
2010-09-01
影响因子：
39.3
通讯作者：
Jondeau, Guillaume
中科院分区：
文献类型：
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作者：
Detaint, Delphine;Faivre, Laurence;Jondeau, Guillaume
在马凡氏综合征和其他1型纤维蛋白病患者中，基因检测变得越来越容易获得，导致在疾病早期发现突变。本研究评估了与发现FBN 1突变相关的心血管（CV）风险，共纳入1013例致病性FBN 1突变的先证者，其中965例患者[中位年龄：22岁（11-34），男性53%]有适合分析的数据。升主动脉（AA）扩张的患者百分比随着年龄的增加而稳步增加，60岁时达到96%（95% CI：94-97%）。主动脉事件（夹层或预防性手术）在20年前很少见，然后逐渐增加，到60年达到74%（95% CI：67-81%）。与女性相比，男性发生AA扩张的风险更高[< 30岁：57%]。（95% CI：52-63）vs. 50%（95% CI：45-55），P = 0.0076]和主动脉事件[< 30岁：21%（95% CI：17-26）vs. 11%（95% CI：8-16），P < 0.0001;校正HR：1.4（1.1-1.8），P = 0.005]。二尖瓣（MV）脱垂[< 60岁：77%（95% CI：72-82）]和MV返流[< 60岁：61%（95% CI：53-69）]的患病率也随年龄稳步增加，但仅限于MV的手术仍然罕见[< 60岁：13%（95% CI：8-21）]。性别间差异无统计学意义（均P > 0.20）。从1985年到2005年，AA扩张的患病率保持稳定（趋势P = 0.88），而AA夹层患者的百分比显著下降（趋势P = 0.01）。CV风险在FBN 1基因突变患者中仍然很重要，并且终生存在，这证明定期主动脉监测是合理的。主动脉扩张或夹层应始终引起对遗传背景的怀疑，从而导致对主动脉外特征的彻底检查和全面的家系调查。
In patients with Marfan syndrome and other type-1 fibrillinopathies, genetic testing is becoming more easily available, leading to the identification of mutations early in the course of the disease. This study evaluates the cardiovascular (CV) risk associated with the discovery of a fibrillin-1 (FBN1) mutation.A total of 1013 probands with pathogenic FBN1 mutations were included, among whom 965 patients [median age: 22 years (11-34), male gender 53%] had data suitable for analysis. The percentage of patients with an ascending aortic (AA) dilatation increased steadily with increasing age and reached 96% (95% CI: 94-97%) by 60 years. The presence of aortic events (dissection or prophylactic surgery) was rare before 20 years and then increased progressively, reaching 74% (95% CI: 67-81%) by 60 years. Compared with women, men were at higher risk for AA dilatation [< 30 years: 57% (95% CI: 52-63) vs. 50% (95% CI: 45-55), P = 0.0076] and aortic events [< 30 years: 21% (95% CI: 17-26) vs. 11% (95% CI: 8-16), P < 0.0001; adjusted HR: 1.4 (1.1-1.8), P = 0.005]. The prevalence of mitral valve (MV) prolapse [< 60 years: 77% (95% CI: 72-82)] and MV regurgitation [< 60 years: 61% (95% CI: 53-69)] also increased steadily with age, but surgery limited to the MV remained rare [< 60 years: 13% (95% CI: 8-21)]. No difference between genders was observed (for all P > 0.20). From 1985 to 2005 the prevalence of AA dilatation remained stable (P for trend = 0.88), whereas the percentage of patients with AA dissection significantly decreased (P for trend = 0.01).The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring. Aortic dilatation or dissection should always trigger suspicion of a genetic background leading to thorough examination for extra-aortic features and comprehensive pedigree investigation.