{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:30:26Z","timestamp":1791203426045,"version":"4.2.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates losartan effectiveness in genetically classified subgroups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              In this predefined substudy of COMPARE, Marfan patients were randomized to daily receive losartan 100 mg or no losartan. Aortic root dimensions were measured by MRI at baseline and after 3 years.\n              <jats:italic>FBN1<\/jats:italic>\n              mutations were classified based on fibrillin-1 protein effect into (1) haploinsufficiency, decreased amount of normal fibrillin-1, or (2) dominant negative, normal fibrillin-1 abundance with mutant fibrillin-1 incorporated in the matrix. A pathogenic\n              <jats:italic>FBN1<\/jats:italic>\n              mutation was found in 117 patients, of whom 79 patients were positive for a dominant negative mutation (67.5%) and 38 for a mutation causing haploinsufficiency (32.5%). Baseline characteristics between treatment groups were similar. Overall, losartan significantly reduced aortic root dilatation rate (no losartan, 1.3\u00b11.5 mm\/3 years, n=59 versus losartan, 0.8\u00b11.4 mm\/3 years, n=58;\n              <jats:italic>P<\/jats:italic>\n              =0.009). However, losartan reduced only aortic root dilatation rate in haploinsufficient patients (no losartan, 1.8\u00b11.5 mm\/3 years, n=21 versus losartan 0.5\u00b10.8 mm\/3 years, n=17;\n              <jats:italic>P<\/jats:italic>\n              =0.001) and not in dominant negative patients (no losartan, 1.2\u00b11.7 mm\/3 years, n=38 versus losartan 0.8\u00b11.3 mm\/3 years, n=41;\n              <jats:italic>P<\/jats:italic>\n              =0.197).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Marfan patients with haploinsufficient\n              <jats:italic>FBN1<\/jats:italic>\n              mutations seem to be more responsive to losartan therapy for inhibition of aortic root dilatation rate compared with dominant negative patients. Additional treatment strategies are needed in Marfan patients with dominant negative\n              <jats:italic>FBN1<\/jats:italic>\n              mutations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.trialregister.nl\/trialreg\/index.asp\">http:\/\/www.trialregister.nl\/trialreg\/index.asp<\/jats:ext-link>\n              ; Unique Identifier: NTR1423.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.114.000950","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T04:45:44Z","timestamp":1421988344000},"page":"383-388","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":164,"title":["Beneficial Outcome of Losartan Therapy Depends on Type of\n            <i>FBN1<\/i>\n            Mutation in Marfan Syndrome"],"prefix":"10.1161","volume":"8","author":[{"given":"Romy","family":"Franken","sequence":"first","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W.","family":"den Hartog","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Radonic","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Micha","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Maugeri","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleur S.","family":"van Dijk","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne E.","family":"Meijers-Heijboer","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Timmermans","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur J.","family":"Scholte","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Groenink","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.M.","family":"Mulder","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeilko H.","family":"Zwinderman","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"de Waard","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pals","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology (R.F., A.W.d.H., M.G., B.J.M.M.), Radiology (M.G.), Clinical Epidemiology and Biostatistics (A.H.Z.), and Medical Biochemistry (V.d.W.), Academic Medical Center Amsterdam, Amsterdam; Interuniversity Cardiology Institute of the Netherlands, Utrecht (R.F., A.W.d.H., M.G., B.J.M.M.); Departments of Pathology (T.R.) and Clinical Genetics (D.M., A.M., F.S.v.D., H.E.M.-H., G.P.), VU University Medical Center, Amsterdam; Department of Cardiology, Radboud University..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht334"},{"key":"e_1_3_3_4_2","unstructured":"http:\/\/omim.org\/entry\/154700"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.08.001"},{"key":"e_1_3_3_6_2","first-page":"1","article-title":"Diagnosis and genetics of Marfan syndrome.","author":"Franken R","year":"2014","unstructured":"Franken R, Heesterbeek TJ, de Waard V, Zwinderman AH, Pals G, Mulder BJ, et al.. 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