{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:29:28Z","timestamp":1768451368678,"version":"3.49.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007190","name":"Sveriges Regering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Marfan Syndrome (MFS) has been associated with increased aortic stiffness and left ventricular dysfunction. The latter may be due to the underlying genotype and\/or secondary to aortic stiffening (vascular-ventricular interaction). The aim of this study was to characterize arterial and cardiac function in MFS using a multimodal approach.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Prospective observational study of MFS patients and healthy controls. Methods included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection, carotid-femoral pulse wave velocity [cfPWV]), reactive hyperemia index [RHI], and biomarker analysis (Olink, CVII panel).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We included 20 patients with MFS and 67 controls. Ascending aortic distensibility, cIMT and RHI were decreased, while all parameters of arterial wave reflection, stiffness and BNP levels were increased in the MFS group. Both systolic and diastolic function were impaired relative to controls. Within the MFS group, no significant correlation between arterial and cardiac function was identified. However, cfPWV correlated significantly with indexed left ventricular mass and volume in MFS. Bran natriuretic peptide (BNP) was the only biomarker significantly elevated in MFS following correction for age and sex.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> MFS patients have generally increased aortic stiffness, endothelial dysfunction and BNP levels while cIMT is decreased, supporting that the mechanism of general stiffening is different from acquired vascular disease. CfPWV is associated with cardiac size, blood pressure and BNP in MFS patients. These may be early markers of disease progression that are suitable for monitoring pharmacological treatment effects in MFS patients.<\/jats:p>","DOI":"10.3389\/fphys.2022.873373","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T07:13:34Z","timestamp":1650870814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Comprehensive Characterization of Arterial and Cardiac Function in Marfan Syndrome\u2014Can Biomarkers Help Improve Outcome?"],"prefix":"10.3389","volume":"13","author":[{"given":"Constance G.","family":"Weismann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Hlebowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"\u00c5kesson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petru","family":"Liuba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Hanseus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1001\/jama.298.13.1539","article-title":"Effect of Perindopril on Large Artery Stiffness and Aortic Root Diameter in Patients with Marfan Syndrome: A Randomized Controlled Trial","volume":"298","author":"Ahimastos","year":"2007","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.amjcard.2020.04.034","article-title":"Meta-analysis Examining the Usefulness of Angiotensin Receptor Blockers for the Prevention of Aortic Root Dilation in Patients with the Marfan Syndrome","volume":"128","author":"Al-Abcha","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1093\/eurjhf\/hfq127","article-title":"Evidence for Marfan Cardiomyopathy","volume":"12","author":"Alpendurada","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"B4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1177\/1358863x15569868","article-title":"Distinct Effects of Losartan and Atenolol on Vascular Stiffness in Marfan Syndrome","volume":"20","author":"Bhatt","year":"2015","journal-title":"Vasc. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.atherosclerosis.2005.01.030","article-title":"Evidence of Vascular Dysfunction in Young Patients with Successfully Repaired Coarctation of Aorta","volume":"182","author":"Brili","year":"2005","journal-title":"Atherosclerosis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1159\/000452448","article-title":"Large Artery Stiffness Assessment Using SphygmoCor Technology","volume":"4","author":"Butlin","year":"2017","journal-title":"Pulse (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/sj.bjp.0707181","article-title":"Endothelial Dysfunction and Compromised eNOS\/Akt Signaling in the Thoracic Aorta during the Progression of Marfan Syndrome","volume":"150","author":"Chung","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1161\/atvbaha.114.304412","article-title":"Vascular Smooth Muscle Cell Phenotypic Changes in Patients with Marfan Syndrome","volume":"35","author":"Crosas-Molist","year":"2015","journal-title":"Atvb"},{"key":"B9","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.cjco.2020.12.018","article-title":"Aortic Dimensions, Biophysical Properties, and Plasma Biomarkers in Children and Adults with Marfan or Loeys-Dietz Syndrome","volume":"3","author":"Cui","year":"2021","journal-title":"CJC Open"},{"key":"B10","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1136\/hrt.2005.071720","article-title":"Variability of Aortic Stiffness Is Not Associated with the Fibrillin 1 Genotype in Patients with Marfan's Syndrome","volume":"92","author":"De Backer","year":"2006","journal-title":"Heart"},{"key":"B11","doi-asserted-by":"publisher","first-page":"I165","DOI":"10.1161\/hc37t1.094900","article-title":"Vascular Dysfunction after Repair of Coarctation of the Aorta: Impact of Early Surgery","volume":"104","author":"de Divitiis","year":"2001","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1016\/s0735-1097(03)00480-7","article-title":"Ambulatory Blood Pressure, Left Ventricular Mass, and Conduit Artery Function Late after Successful Repair of Coarctation of the Aorta","volume":"41","author":"de Divitiis","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/j.amjcard.2010.05.009","article-title":"Vascular Function in Children with Repaired Tetralogy of Fallot","volume":"106","author":"de Groot","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1017\/s1047951117001950","article-title":"Aortic Elasticity and Carotid Intima-media Thickness in Children with Mitral Valve Prolapse","volume":"28","author":"Erolu","year":"2018","journal-title":"Cardiol. Young"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1093\/eurheartj\/ehv739","article-title":"Genotype Impacts Survival in Marfan Syndrome","volume":"37","author":"Franken","year":"2016","journal-title":"Eur. Heart J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13023-015-0369-8","article-title":"Prevalence, Incidence, and Age at Diagnosis in Marfan Syndrome","volume":"10","author":"Groth","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1177\/2047487317737174","article-title":"Increased Arterial Stiffness in Children with Congenital Heart Disease","volume":"25","author":"H\u00e4cker","year":"2018","journal-title":"Eur. J. Prev. Cardiolog"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1161\/circulationaha.107.748574","article-title":"Cross-sectional Relations of Digital Vascular Function to Cardiovascular Risk Factors in the Framingham Heart Study","volume":"117","author":"Hamburg","year":"2008","journal-title":"Circulation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1016\/j.ijcard.2012.06.036","article-title":"Prospective Risk Stratification of Sudden Cardiac Death in Marfan's Syndrome","volume":"167","author":"Hoffmann","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.ahj.2011.03.029","article-title":"Relationship of Aortic Pulse Wave Velocity and Baroreceptor Reflex Sensitivity to Blood Pressure Control in Patients with Repaired Coarctation of the Aorta","volume":"162","author":"Kenny","year":"2011","journal-title":"Am. Heart J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1540-8175.2008.00813.x","article-title":"Assessment of Carotid Compliance Using Real Time Vascular Ultrasound Image Analysis in Marfan Syndrome","volume":"26","author":"Kiotsekoglou","year":"2009","journal-title":"Echocardiography"},{"key":"B22","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/j.1540-8175.2010.01241.x","article-title":"Assessment of Aortic Stiffness in Marfan Syndrome Using Two-Dimensional and Doppler Echocardiography","volume":"28","author":"Kiotsekoglou","year":"2011","journal-title":"Echocardiography"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e0164778","DOI":"10.1371\/journal.pone.0164778","article-title":"Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome","volume":"11","author":"Lee","year":"2016","journal-title":"PloS one"},{"key":"B24","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The Revised Ghent Nosology for the Marfan Syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"965","DOI":"10.3389\/fphys.2018.00965","article-title":"The Evaluation of Flow-Mediated Vasodilation in the Brachial Artery Correlates with Endothelial Dysfunction Evaluated by Nitric Oxide Synthase Metabolites in Marfan Syndrome Patients","volume":"9","author":"Lomel\u00ed","year":"2018","journal-title":"Front. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e006979","DOI":"10.1161\/CIRCIMAGING.117.006979","article-title":"Relationship of Echocardiographic Z Scores Adjusted for Body Surface Area to Age, Sex, Race, and Ethnicity: The Pediatric Heart Network Normal Echocardiogram Database","volume":"10","author":"Lopez","year":"2017","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B27","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1017\/s1047951112001114","article-title":"Predictors of Exaggerated Exercise-Induced Systolic Blood Pressures in Young Patients after Coarctation Repair","volume":"23","author":"Madueme","year":"2013","journal-title":"Cardiol. Young"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e002270","DOI":"10.1161\/JAHA.115.002270","article-title":"Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis","volume":"4","author":"Matsuzawa","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"B29","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.ijcard.2015.02.011","article-title":"Increased Aortic Blood Pressure Augmentation in Patients with Congenital Heart Defects - A Cross-Sectional Study in 1125 Patients and 322 Controls","volume":"184","author":"M\u00fcller","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/s0002-8703(00)90045-0","article-title":"Peripheral Resistance Vessel Dysfunction in Marfan Syndrome","volume":"139","author":"Nakamura","year":"2000","journal-title":"Am. Heart J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1536\/ihj.17-564","article-title":"Endothelial Dysfunction of Conduit Arteries in Patients with Repaired Coarctation of the Aorta","volume":"59","author":"Nozaki","year":"2018","journal-title":"Int. Heart J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1136\/heartjnl-2014-305739","article-title":"Endothelial Function in Contemporary Patients with Repaired Coarctation of Aorta","volume":"100","author":"Radke","year":"2014","journal-title":"Heart"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e91588","DOI":"10.1172\/jci.insight.91588","article-title":"Nonmyocyte ERK1\/2 Signaling Contributes to Load-Induced Cardiomyopathy in Marfan Mice","volume":"2","author":"Rouf","year":"2017","journal-title":"JCI Insight"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/eurheartj\/ehq010","article-title":"Assessment of Endothelial Function by Non-invasive Peripheral Arterial Tonometry Predicts Late Cardiovascular Adverse Events","volume":"31","author":"Rubinshtein","year":"2010","journal-title":"Eur. Heart J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ehjci\/jeab069","article-title":"Aortic Flow Dynamics and Stiffness in Loeys-Dietz Syndrome Patients: A Comparison with Healthy Volunteers and Marfan Syndrome Patients","author":"Ruiz-Mu\u00f1oz","year":"2021","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"B36","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1093\/ejcts\/ezr032","article-title":"Marked Disparity in Mechanical wall Properties between Ascending and Descending Aorta in Patients with Tetralogy of Fallot","volume":"41","author":"Saiki","year":"2012","journal-title":"Eur. J. cardio-thoracic Surg. : official J. Eur. Assoc. Cardio-thoracic Surg."},{"key":"B37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1097\/hjh.0000000000001512","article-title":"Aortic Dilatation in Marfan Syndrome: Role of Arterial Stiffness and Fibrillin-1 Variants","volume":"36","author":"Salvi","year":"2018","journal-title":"J. Hypertens."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1016\/j.hlc.2021.07.018","article-title":"Arterial Stiffness in Congenital Heart Disease","volume":"30","author":"Sandhu","year":"2021","journal-title":"Heart Lung Circ."},{"key":"B39","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1093\/ejcts\/ezy168","article-title":"Aortic Stiffness in Adolescent Turner and Marfan Syndrome Patients","volume":"54","author":"Sch\u00e4fer","year":"2018","journal-title":"Eur. J. cardio-thoracic Surg. : official J. Eur. Assoc. Cardio-thoracic Surg."},{"key":"B40","first-page":"17","article-title":"Aortic wall Thickness: An Independent Risk Factor for Aortic Dissection?","volume":"23","author":"Shiran","year":"2014","journal-title":"J. Heart Valve Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s00418-018-1686-5","article-title":"A Heart for Fibrillin: Spatial Arrangement in Adult Wild-type Murine Myocardial Tissue","volume":"150","author":"Steijns","year":"2018","journal-title":"Histochem. Cel Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1111\/j.1476-5381.2009.00439.x","article-title":"Dysfunction of Endothelial and Smooth Muscle Cells in Small Arteries of a Mouse Model of Marfan Syndrome","volume":"158","author":"Syyong","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1007\/s00380-013-0393-3","article-title":"Impairment of Flow-Mediated Dilation Correlates with Aortic Dilation in Patients with Marfan Syndrome","volume":"29","author":"Takata","year":"2014","journal-title":"Heart Vessels"},{"key":"B44","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1161\/circheartfailure.108.785279","article-title":"Elevated Afterload, Neuroendocrine Stimulation, and Human Heart Failure Increase BNP Levels and Inhibit Preload-dependent SERCA Upregulation","volume":"1","author":"Toischer","year":"2008","journal-title":"Circ. Heart Fail."},{"key":"B45","doi-asserted-by":"publisher","first-page":"643900","DOI":"10.3389\/fcvm.2021.643900","article-title":"Multimodal Assessment of Vascular and Ventricular Function in Children and Adults with Bicuspid Aortic Valve Disease","volume":"8","author":"Weismann","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ijcard.2020.08.095","article-title":"Multimodal Assessment of Vascular and Ventricular Function in Children and Adults with Repaired Aortic Coarctation","volume":"323","author":"Weismann","year":"2021","journal-title":"Int. J. Cardiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1002\/jmri.22646","article-title":"Age-related and Regional Changes of Aortic Stiffness in the Marfan Syndrome: Assessment with Velocity-Encoded MRI","volume":"34","author":"Westenberg","year":"2011","journal-title":"J. Magn. Reson. Imaging"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3266","DOI":"10.3390\/jcm10153266","article-title":"Association between Objectively Measured Physical Activity and Arterial Stiffness in Children with Congenital Heart Disease","volume":"10","author":"Willinger","year":"2021","journal-title":"J. Clin. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1161\/01.cir.99.7.909","article-title":"Endothelial Function in Marfan Syndrome: Selective Impairment of Flow-Mediated Vasodilation","volume":"99","author":"Wilson","year":"1999","journal-title":"Circulation"},{"key":"B50","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1097\/mca.0000000000000094","article-title":"Comparison of Peripheral Arterial Tonometry and Flow-Mediated Vasodilation for Assessment of the Severity and Complexity of Coronary Artery Disease","volume":"25","author":"Woo","year":"2014","journal-title":"Coron. Artery Dis."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.873373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T07:13:40Z","timestamp":1650870820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.873373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,25]]},"references-count":50,"alternative-id":["10.3389\/fphys.2022.873373"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.873373","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,25]]},"article-number":"873373"}}