TY - JOUR
T1 - Cardiovascular manifestations in men and women carrying a FBN1 mutation
AU - Détaint, Delphine
AU - Faivre, Laurence
AU - Collod-Beroud, Gwenaelle
AU - Child, Anne H.
AU - Loeys, Bart L.
AU - Binquet, Christine
AU - Gautier, Elodie
AU - Arbustini, Eloisa
AU - Mayer, Karin
AU - Arslan-Kirchner, Mine
AU - Stheneur, Chantal
AU - Halliday, Dorothy
AU - Beroud, Christophe
AU - Bonithon-Kopp, Claire
AU - Claustres, Mireille
AU - Plauchu, Henri
AU - Robinson, Peter N.
AU - Kiotsekoglou, Anatoli
AU - De Backer, Julie
AU - Ads, Lesley
AU - Francke, Uta
AU - De Paepe, Anne
AU - Boileau, Catherine
AU - Jondeau, Guillaume
PY - 2010/9
Y1 - 2010/9
N2 - AimsIn 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. Methods and resultsA 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). ConclusionThe 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.
AB - AimsIn 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. Methods and resultsA 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). ConclusionThe 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.
KW - Aortic dilatation
KW - Aortic dissection
KW - Cardiovascular risk
KW - FBN1 gene mutation
KW - Marfan syndrome
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U2 - 10.1093/eurheartj/ehq258
DO - 10.1093/eurheartj/ehq258
M3 - Article
C2 - 20709720
AN - SCOPUS:77956914239
VL - 31
SP - 2223
EP - 2229
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 18
ER -